Bronchogenic Carcinoma

TOKYO, Japan & BASKING RIDGE, NJ, USA I October 30, 2024 I The first patients have been dosed in three global, randomized phase 3 trials evaluating the efficacy and safety of datopotamab deruxtecan (Dato-DXd)-based combinations in patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN). TROPION-Lung10 is evaluating datopotamab deruxtecan plus rilvegostomig, AstraZeneca’s PD-1/TIGIT bispecific antibody, or rilvegostomig alone versus pembrolizumab in patients with previously untreated locally advanced or metastatic nonsquamous NSCLC with high PD-L1 expression (tumor cells [TC] ≥ 50%) and without actionable genomic alterations. TROPION-Lung14 is evaluating datopotamab deruxtecan plus osimertinib, AstraZeneca’s EGFR tyrosine kinase inhibitor (TKI), versus osimertinib alone in patients with previously untreated locally advanced or metastatic EGFR mutated nonsquamous NSCLC. TROPION-Lung15 is evaluating datopotamab deruxtecan with or without osimertinib versus platinum-based doublet chemotherapy in patients with locally advanced or metastatic nonsquamous EGFR mutated NSCLC whose disease progressed on prior treatment with osimertinib. “These three trials in either high PD-L1 expressing or EGFR mutated nonsquamous non-small cell lung cancer are critical to helping us understand the potential role of datopotamab deruxtecan in treating patients across different lines and types of lung cancer,” said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. “Our growing TROPION clinical program, which now consists of seven phase 3 trials demonstrates our commitment to understanding the full potential of datopotamab deruxtecan in lung cancer.” “Clinical research suggests that combining an antibody drug conjugate with a targeted treatment or a bispecific immunotherapy may drive stronger and more durable tumor responses in patients with a variety of cancers including lung cancer,” said Cristian Massacesi, MD, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca. “The initiation of these additional three phase 3 trials of datopotamab deruxtecan in combination with our agents, osimertinib and rilvegostomig illustrates our commitment to exploring potential synergies within our oncology pipeline as well as the full potential and combinability of this TROP2 directed antibody drug conjugate across multiple segments and settings of non-small cell lung cancer.” About TROPION-Lung10 TROPION-Lung10 is a global, multicenter, open-label, three-arm phase 3 trial where patients will be randomized in a 2:1:2 ratio to evaluate the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) in combination with rilvegostomig (750 mg) or rilvegostomig (750 mg) monotherapy versus pembrolizumab (200 mg) monotherapy in adult patients with previously untreated locally advanced or metastatic nonsquamous NSCLC with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations. The dual primary endpoints of TROPION-Lung10 are progression-free survival (PFS) as assessed by blinded independent central review (BICR) and overall survival (OS) in patients with TROP2 positive tumors receiving datopotamab deruxtecan in combination with rilvegostomig versus the pembrolizumab arm. A pre-specified retrospective analysis from tumor biopsies collected pretreatment will be conducted following validation of a potential TROP2 biomarker determined by quantitative continuous scoring, a computational pathology approach. Key secondary endpoints for all arms of the trial include PFS as assessed by BICR and investigator and OS in the intention-to-treat (ITT) population, objective response rate (ORR) as assessed by BICR and duration of response (DoR) as assessed by BICR and investigator in both TROP2 biomarker positive and the ITT populations. The safety and tolerability of datopotamab deruxtecan in combination with rilvegostomig and rilvegostomig monotherapy as compared with pembrolizumab also will be assessed. TROPION-Lung10 will enroll approximately 675 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov . The TIGIT component of rilvegostomig is derived from the clinical-stage anti-TIGIT antibody, COM902, developed by Compugen Ltd. (Nasdaq/TASE: CGEN). About TROPION-Lung14 TROPION-Lung14 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) in combination with osimertinib (80 mg) versus osimertinib (80 mg) monotherapy in adult patients with previously untreated locally advanced or metastatic nonsquamous NSCLC with an EGFR mutation (Exon 19 deletion and/or L858R). The randomized period of the trial is preceded by a single-arm safety run-in period which will enroll approximately 20 patients to evaluate the combination therapy. The primary endpoint of TROPION-Lung14 is PFS as assessed by BICR. Key secondary endpoints include central nervous system (CNS) PFS as assessed by CNS BICR, PFS as assessed by investigator, ORR as assessed by BICR and investigator, OS and safety. TROPION-Lung14 will enroll approximately 580 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov . About TROPION-Lung15 TROPION-Lung15 is a global, multicenter, open-label, three-arm phase 3 trial where patients will be randomized in a 1:1:1 ratio to evaluate the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) as monotherapy or in combination with osimertinib (80 mg) versus platinum-based doublet chemotherapy (pemetrexed in combination with carboplatin or cisplatin followed by pemetrexed maintenance) in adult patients with locally advanced or metastatic nonsquamous NSCLC with at least one EGFR mutation (G719X, Ex19del, S768I, L858R, and/or L861Q) and with disease progression following prior treatment with osimertinib. The dual primary PFS endpoints of TROPION-Lung15 are PFS as assessed by BICR for datopotamab deruxtecan monotherapy versus chemotherapy and datopotamab deruxtecan in combination with osimertinib versus chemotherapy. Key secondary endpoints include investigator-assessed CNS PFS as assessed by CNS BICR, ORR and DoR as assessed by BICR, OS and safety. TROPION-Lung15 will enroll approximately 630 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov . About Advanced Non-Small Cell Lung Cancer Nearly 2.5 million lung cancer cases were diagnosed globally in 2022. 1 NSCLC is the most common type of lung cancer, accounting for about 85% of cases. 2 Approximately 75% and 25% of NSCLC tumors are of nonsquamous or squamous histology, respectively, with EGFR mutations occurring in 14% to 38% of all NSCLC tumors worldwide. 3,4 A majority of EGFR mutations occur in tumors with nonsquamous histology. 5 For patients with tumors that do not express a known actionable genomic alteration (e.g., EGFR, ALK, ROS1, NTRK, BRAF, RET or MET), the current first-line standard of care in the metastatic setting is an immune checkpoint inhibitor and/or platinum-based chemotherapy based on PD-L1 expression. 6,7,8 For certain patients with tumors that have EGFR mutations, the established first-line treatment in the metastatic setting is an EGFR TKI. 9 While these treatment strategies have improved outcomes in the first-line metastatic setting, most patients eventually experience disease progression. 10,11,12 TROP2 is a protein broadly expressed in the majority of NSCLC tumors. 13 There is currently no TROP2 directed ADC approved for the treatment of lung cancer. 8,9 About Datopotamab Deruxtecan (Dato-DXd) Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple negative breast cancer and HR positive, HER2 negative breast cancer. The program includes seven phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings. About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan (Dato-DXd) in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo. The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform. Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com . References 1 World Health Organization. Global Cancer Observatory: Lung . Accessed October 2024. 2 Economopoulou P, et al. Ann Transl Med . 2018; 6(8):138 3 National Cancer Institute. SEER Cancer Statistics Factsheets: Lung and Bronchus Cancer, CSR 1975-2017 . Accessed October 2024. 4 Pretelli G, et al. Int J Mol Sci . 2023; 24, 8878. 5 Prabhakar C. Translational Lung Cancer Research . 2015; 4(2), 110-118. 6 Mok TSK, et al. Lancet . 2019 May 4;393(10183):1819-1830. 7 Brahmer J.R. et al. KEYNOTE-024 5-year OS update . ESMO 2021 Virtual Congress. 2021 Sept 16 – 20; Abstract LBA51. 8 Rodríguez-Abreau D, et al. Ann Onc . 2021 Jul;32(7):881-895. 9 American Cancer Society. Targeted Drug Therapy for Non-Small Cell Lung Cancer . Accessed October 2024. 10 Chen R, et al. J Hematol Oncol . 2020:13(1):58. 11 Majeed U, et al. J Hematol Oncol . 2021;14(1):108. 12 Pircher A, et al. Anticancer Research . 2020;70(5):287-294. 13 Mito R, et al. Pathol Int . 2020;70(5):287-294. SOURCE: Daiichi Sankyo

TOKYO & BASKING RIDGE, N.J.--( BUSINESS WIRE )--Detailed results from the TROPION-Lung01 phase 3 trial showed a clinically meaningful trend toward improving overall survival (OS) with datopotamab deruxtecan (Dato-DXd) compared to docetaxel, the current standard of care chemotherapy, in adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) treated with at least one prior line of therapy. Results will be presented today during an oral presentation ( OA08.03 ) at the IASLC 2024 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (#WCLC24) and simultaneously published in the Journal of Clinical Oncology . Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN). In the overall trial population, OS results numerically favored datopotamab deruxtecan compared to docetaxel (median OS 12.9 months versus 11.8 months) but did not reach statistical significance (hazard ratio [HR] =0.94; 95% confidence interval [CI]: 0.78-1.14; p=0.530). In the pre-specified subgroup of patients with nonsquamous NSCLC, datopotamab deruxtecan showed a 2.3 month improvement in OS compared to docetaxel (14.6 months versus 12.3 months; HR=0.84; 95% CI: 0.68-1.05). In patients with nonsquamous NSCLC, OS improvement was observed regardless of the presence of actionable genomic alterations. In patients with squamous NSCLC, datopotamab deruxtecan did not show an OS improvement, consistent with the previous analysis. “ Despite many efforts to surpass docetaxel with novel approaches in previously treated advanced or metastatic non-small cell lung cancer, patients only survive for about one year,” said Jacob Sands, MD, Dana-Farber Cancer Institute, Medical Oncology and investigator in the trial. “ For datopotamab deruxtecan to show a statistically significant improvement in progression-free survival along with improved response rate, duration of response and an overall survival improvement numerically consistent with progression-free survival is clinically meaningful for patients with nonsquamous lung cancer.” The safety profile of datopotamab deruxtecan in TROPION-Lung01 was consistent with the previous analysis including lower rates of dose reduction (20% vs. 30%) and discontinuation (8% vs. 12%) due to adverse events compared to docetaxel. The median treatment duration for datopotamab deruxtecan was 4.2 months versus 2.8 months for docetaxel. Grade 3 or higher treatment-related adverse events (TRAE) occurred in 26% and 42% of patients in the datopotamab deruxtecan and docetaxel arms, respectively. The most common grade 3 or higher TRAEs for datopotamab deruxtecan versus docetaxel were neutropenia (1% vs. 23%), leukopenia (0% vs. 13%), stomatitis (7% vs. 1%), anemia (4% vs. 4%), interstitial lung disease (ILD) (4% vs. 1%) and asthenia (3% vs. 2%). No new ILD events of any grade were adjudicated as drug-related since the previous analysis. This final analysis of OS builds on the positive progression-free survival (PFS) results presented at the European Society for Medical Oncology (#ESMO23) 2023 Congress, which showed datopotamab deruxtecan demonstrated a statistically significant improvement in PFS in the overall trial population and a clinically meaningful PFS benefit in patients with nonsquamous NSCLC. The OS data have been shared with health authorities currently reviewing applications for this indication. “ For patients with nonsquamous non-small cell lung cancer, disease progression is common, making this patient population difficult to treat,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “ The data from TROPION-Lung01 demonstrate the potential of datopotamab deruxtecan in this setting and support our comprehensive development program where we also are evaluating this TROP2 directed antibody drug conjugate as part of combination strategies in earlier treatment settings of non-small cell lung cancer.” “ TROPION-Lung01 showed a clinically meaningful trend towards improving the survival of patients with advanced or metastatic nonsquamous non-small cell lung cancer, building on the previously reported progression-free survival data,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “ Together with the data we have presented for the potential TROP2-QCS biomarker and from NeoCOAST-2 in early-stage disease, these results underscore our confidence in the important role datopotamab deruxtecan can play across segments and settings of non-small cell lung cancer.” In TROPION-Lung01, patient enrollment by tumor histology was balanced across treatment arms and consistent with real world incidence with approximately 75% of enrolled patients having nonsquamous NSCLC. 1,2 In the datopotamab deruxtecan arm, patients were previously treated with platinum containing therapy (99%), anti-PD-1/PD-L1 therapy (88%) or targeted therapy (15%). In the docetaxel arm, patients were previously treated with platinum containing therapy (100%), anti-PD-1/PD-L1 therapy (88%) or targeted therapy (16%). In both arms, 17% of patients had tumors expressing actionable genomic alterations, such as epidermal growth factor receptor mutations. Summary of TROPION-Lung01 Overall Survival Results Overall Trial Population Datopotamab Deruxtecan (n=299) Docetaxel (n=305) Median OS (months) (95% CI) i 12.9 months (11.0-13.9) 11.8 months (10.0-12.8) HR (95% CI) 0.94 (0.78-1.14) p-value 0.530 Pre-specified boundary (2-sided) 0.045 Nonsquamous Histology Datopotamab Deruxtecan (n=234) Docetaxel (n=234) Median OS (months) (95% CI) i 14.6 months (12.4-16.0) 12.3 months (10.7-14.0) HR (95% CI) 0.84 (0.68-1.05) OS Probability at 12 months (%) (95% CI) 58.8% (52.0-64.9) 52.8% (45.9-59.2) OS Probability at 24 months (%) (95% CI) 29.0% (22.8-35.5) 21.7% (16.0-28.0) Nonsquamous Histology - with Actionable Genomic Alterations Datopotamab Deruxtecan (n=48) Docetaxel (n=50) Median OS (months) (95% CI) i 15.6 months 9.8 months HR (95% CI) 0.65 (0.40-1.08) Nonsquamous Histology - without Actionable Genomic Alterations Datopotamab Deruxtecan (n=186) Docetaxel (n=184) Median OS (months) (95% CI) i 13.6 months 12.3 months HR (95% CI) 0.89 (0.70-1.13) Squamous Histology Datopotamab Deruxtecan (n=65) Docetaxel (n=71) Median OS (months) (95% CI) i 7.6 months (5.0-11.0) 9.4 months (7.2-12.5) Hazard Ratio (95% CI) 1.32 (0.91-1.92) CI, confidence interval; HR, hazard ratio; OS, overall survival i Median follow-up was 23.1 months for both the datopotamab deruxtecan and docetaxel arms Results from an exploratory analysis of TROPION-Lung01 were featured in a WCLC Presidential Symposium ( PL02.11 ) on September 8 which showed TROP2 as measured by AstraZeneca’s proprietary computational pathology platform, quantitative continuous scoring (QCS), was predictive of clinical outcomes in patients with advanced or metastatic NSCLC treated with datopotamab deruxtecan. Datopotamab deruxtecan plus durvalumab and chemotherapy showed promising response rates in patients with early-stage resectable NSCLC Results from the NeoCOAST-2 phase 2 platform trial evaluating durvalumab in multiple novel combinations, before and after surgery, in patients with early-stage (stage IIA-IIIB) resectable NSCLC were featured in a WCLC Presidential Symposium ( PL02.07 ). Preliminary results from the trial arm testing neoadjuvant durvalumab plus datopotamab deruxtecan and carboplatin demonstrated a pathological complete response (pCR) rate of 34.1% (95% CI: 20.5-49.9) and a major pathological response (mPR) rate of 65.9% (95% CI: 50.1-79.5). This was numerically higher than response rates shown by other combination regimens tested; however, the trial was not powered to make direct statistical comparisons between arms. The safety profile of durvalumab plus datopotamab deruxtecan and carboplatin was consistent with the known safety profiles of these agents with grade 3 or higher TRAEs occurring in 18.5% of patients. Surgical rates across arms were comparable and in line with those shown in recent phase 3 trials. Daiichi Sankyo and AstraZeneca are evaluating datopotamab deruxtecan in combination with durvalumab in multiple ongoing trials. About TROPION-Lung01 TROPION-Lung01 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) versus docetaxel (75 mg/m 2 ) in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. Patients with actionable genomic alterations were previously treated with an approved targeted therapy and platinum-based chemotherapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. The dual primary endpoints of TROPION-Lung01 are PFS as assessed by blinded independent central review (BICR) and OS. Key secondary endpoints include investigator-assessed PFS, objective response rate (ORR), duration of response, time to response, disease control rate as assessed by both BICR and investigator, and safety. TROPION-Lung01 enrolled approximately 600 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov . About NeoCOAST-2 NeoCOAST-2 is a global, randomized, multicenter, open-label, multi-arm phase 2 platform trial evaluating the efficacy and safety of durvalumab in multiple novel combinations, before and after surgery, in patients with resectable, early-stage (stage IIA-IIIB) NSCLC. The dual primary endpoints of NeoCOAST-2 are antitumor activity of neoadjuvant treatment assessed by pCR and the safety and tolerability of neoadjuvant and adjuvant treatment. Key secondary endpoints include event-free survival, disease-free survival and ORR as assessed by both RECIST version 1.1 and investigator, OS, tumor resection and mPR as defined by central blinded independent pathologist review. NeoCOAST-2 will enroll approximately 490 patients in Asia, Europe and North America. For more information visit ClinicalTrials.gov . About Advanced Non-Small Cell Lung Cancer Nearly 2.5 million lung cancer cases were diagnosed globally in 2022. 1 NSCLC is the most common type of lung cancer, accounting for about 80% of cases. 2 Approximately 75% and 25% of NSCLC tumors are of nonsquamous or squamous histology, respectively. 3 While immunotherapy and targeted therapies have improved outcomes in the first-line metastatic setting, most patients eventually experience disease progression and receive chemotherapy. 4,5,6 For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC, despite limited effectiveness and known side effects. 4,5,6 TROP2 is a protein broadly expressed in the majority of NSCLC tumors. 7 There is currently no TROP2 directed ADC approved for the treatment of lung cancer. 8,9 About Datopotamab Deruxtecan (Dato-DXd) Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple negative breast cancer and HR positive, HER2 negative breast cancer. The program includes seven phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings. About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan (Dato-DXd) in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo. The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform. Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com . _______________________________ References 1 World Health Organization. Global Cancer Observatory: Lung. Accessed September 2024. 2 Cancer.net. Lung Cancer – Non-Small Cell: Statistics . Accessed September 2024. 3 National Cancer Institute. SEER Cancer Statistics Factsheets: Lung and Bronchus Cancer . Accessed September 2024. 4 Chen R, et al. J Hematol Oncol . 2020:13(1):58. 5 Majeed U, et al. J Hematol Oncol . 2021;14(1):108. 6 Pircher A, et al. Anticancer Research . 2020;70(5):287-294. 7 Mito R, et al. Pathol Int . 2020;70(5):287-294. 8 Rodríguez-Abreau D, et al. Ann Onc . 2021 Jul;32(7):881-895. 9 American Cancer Society. Targeted Drug Therapy for Non-Small Cell Lung Cancer . Accessed September 2024.

WILMINGTON, Del.--( BUSINESS WIRE )--Detailed results from the TROPION-Lung01 Phase III trial showed a clinically meaningful trend toward improving overall survival (OS) with datopotamab deruxtecan (Dato-DXd) compared to docetaxel, the current standard of care chemotherapy, in adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) treated with at least one prior line of therapy. These results will be presented today during an oral presentation ( OA08.03 ) at the IASLC 2024 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer. Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo. In the overall trial population, OS results numerically favored datopotamab deruxtecan compared to docetaxel (12.9 vs. 11.8 months) but did not reach statistical significance (hazard ratio [HR] 0.94; 95% confidence interval [CI] 0.78-1.14; p=0.530). In the prespecified subgroup of patients with nonsquamous NSCLC, datopotamab deruxtecan showed a 2.3-month improvement in OS compared to docetaxel (14.6 vs. 12.3 months; HR 0.84; 95% CI 0.68-1.05). In patients with nonsquamous NSCLC, OS improvement was observed regardless of the presence of actionable genomic alterations. In patients with squamous NSCLC, consistent with the previous analysis, datopotamab deruxtecan did not show an OS improvement. Jacob Sands, MD, Dana-Farber Cancer Institute, Medical Oncology and investigator in the trial, said: “ Despite many efforts to surpass docetaxel with novel approaches in previously treated advanced or metastatic non-small cell lung cancer, patients only survive for about one year. For datopotamab deruxtecan to show a statistically significant improvement in progression-free survival along with improved response rate, duration of response and an overall survival improvement numerically consistent with progression-free survival is clinically meaningful for patients with nonsquamous lung cancer.” Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “ TROPION-Lung01 showed a clinically meaningful trend towards improving the survival of patients with advanced or metastatic nonsquamous non-small cell lung cancer, building on the previously reported progression-free survival data. Together with the data we have presented for the potential TROP2-QCS biomarker and from NeoCOAST-2 in early-stage disease, these results underscore our confidence in the important role datopotamab deruxtecan can play across segments and settings of non-small cell lung cancer.” Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “ For patients with nonsquamous non-small cell lung cancer, disease progression is common, making this patient population difficult to treat. The data from TROPION-Lung01 demonstrate the potential of datopotamab deruxtecan in this setting and support our comprehensive development program where we are also evaluating this TROP2-directed antibody drug conjugate as part of combination strategies in earlier treatment settings of non-small cell lung cancer.” The safety profile of datopotamab deruxtecan in TROPION-Lung01 was consistent with the previous analysis including lower rates of dose reduction (20%, 30%) and discontinuation (8%, 12%) due to adverse events compared to docetaxel. The median treatment duration for datopotamab deruxtecan was 4.2 months versus 2.8 months for docetaxel. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 26% and 42% of patients in the datopotamab deruxtecan and docetaxel arms, respectively. The most common Grade 3 or higher TRAEs were neutropenia (1%, 23%), leukopenia (0%, 13%), stomatitis (7%, 1%), anemia (4%, 4%), interstitial lung disease (ILD) (4%, 1%) and asthenia (3%, 2%). No new ILD events of any grade were adjudicated as drug-related since the previous analysis. In TROPION-Lung01, patient enrollment by tumor histology was balanced across treatment arms and consistent with real world incidence with approximately 75% of enrolled patients having nonsquamous NSCLC. 1,2 In both arms, 17% of patients had tumors expressing actionable genomic alterations, such as epidermal growth factor receptor (EGFR) mutations. This final analysis of OS builds on the positive progression-free survival (PFS) results presented at the 2023 European Society for Medical Oncology Congress, which showed datopotamab deruxtecan demonstrated a statistically significant improvement in PFS in the overall trial population and a clinically meaningful PFS benefit in patients with nonsquamous NSCLC. The OS data have been shared with health authorities currently reviewing applications for this indication. Summary of TROPION-Lung01 survival results Overall trial population Datopotamab deruxtecan (n=299) Docetaxel (n=305) Median OS (95% CI) i 12.9 months (11.0-13.9) 11.8 months (10.0-12.8) HR (95% CI) 0.94 (0.78-1.14) p-value 0.530 Pre-specified boundary (2-sided) 0.045 Nonsquamous histology Datopotamab deruxtecan (n=234) Docetaxel (n=234) Median OS (95% CI) i 14.6 months (12.4-16.0) 12.3 months (10.7-14.0) HR (95% CI) 0.84 (0.68-1.05) OS probability at 12 months (95% CI) 58.8% (52.0-64.9) 52.8% (45.9-59.2) OS probability at 24 months (95% CI) 29.0% (22.8-35.5) 21.7% (16.0-28.0) Nonsquamous histology – with actionable genomic alterations Datopotamab deruxtecan (n=48) Docetaxel (n=50) Median OS (95% CI) i 15.6 months 9.8 months HR (95% CI) 0.65 (0.40-1.08) Nonsquamous histology – without actionable genomic alterations Datopotamab deruxtecan (n=186) Docetaxel (n=184) Median OS (95% CI) i 13.6 months 12.3 months HR (95% CI) 0.89 (0.70-1.13) CI, confidence interval; HR, hazard ratio; OS, overall survival i Median follow-up was 23.1 months for both the datopotamab deruxtecan and docetaxel arms Datopotamab deruxtecan plus IMFINZI ® (durvalumab) and chemotherapy showed promising response rates in patients with early-stage resectable NSCLC Results from the NeoCOAST-2 Phase II platform trial evaluating IMFINZI ® (durvalumab) in multiple novel combinations, before and after surgery, in patients with early-stage (Stage IIA–IIIB) resectable NSCLC were featured in a WCLC Presidential Symposium ( PL02.07 ). Preliminary results from the trial arm testing neoadjuvant IMFINZI plus datopotamab deruxtecan and carboplatin demonstrated a pathological complete response (pCR) rate of 34.1% (95% CI 20.5-49.9) and a major pathological response (mPR) rate of 65.9% (95% CI 50.1-79.5). This was numerically higher than the response rates shown by other combination regimens tested, however, the trial was not powered to make direct statistical comparisons between arms. The safety profile of IMFINZI plus datopotamab deruxtecan and carboplatin was consistent with the known safety profiles of these agents. Surgical rates across arms were comparable and in line with those shown in recent Phase III trials. AstraZeneca and Daiichi Sankyo are evaluating datopotamab deruxtecan in combination with IMFINZI in multiple ongoing trials. Also featured in a WCLC Presidential Symposium were results from an exploratory analysis of TROPION-Lung01 which showed TROP2 as measured by AstraZeneca’s proprietary computational pathology platform, quantitative continuous scoring (QCS), was predictive of clinical outcomes in patients with advanced or metastatic NSCLC treated with datopotamab deruxtecan. IMPORTANT SAFETY INFORMATION FOR IMFINZI ® and IMJUDO ® (tremelimumab-actl) There are no contraindications for IMFINZI ® (durvalumab) or IMJUDO ® (tremelimumab-actl). Severe and Fatal Immune-Mediated Adverse Reactions Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and before each dose. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI and IMJUDO depending on severity. See USPI Dosing and Administration for specific details. In general, if IMFINZI and IMJUDO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Immune-Mediated Pneumonitis IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which may be fatal. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. IMFINZI as a Single Agent In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions. In patients who received recent prior radiation, the incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3% (87/475) in patients receiving IMFINZI and 12.8% (30/234) in patients receiving placebo. Of the patients who received IMFINZI (475), 1.1% were fatal and 2.7% were Grade 3 adverse reactions. The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC or BTC when given in combination with chemotherapy. IMFINZI with IMJUDO Immune‑mediated pneumonitis occurred in 1.3% (5/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.3%) and Grade 3 (0.2%) adverse reactions. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated pneumonitis occurred in 3.5% (21/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.5%), and Grade 3 (1%) adverse reactions. Immune-Mediated Colitis IMFINZI with IMJUDO and platinum-based chemotherapy can cause immune-mediated colitis, which may be fatal. IMFINZI and IMJUDO can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. IMFINZI as a Single Agent Immune-mediated colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions. IMFINZI with IMJUDO Immune‑mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (3.6%) adverse reactions. Intestinal perforation has been observed in other studies of IMFINZI and IMJUDO. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated colitis occurred in 6.5% (39/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including fatal (0.2%) and Grade 3 (2.5%) adverse reactions. Intestinal perforation and large intestine perforation were reported in 0.1% of patients. Immune-Mediated Hepatitis IMFINZI and IMJUDO can cause immune-mediated hepatitis, which may be fatal. IMFINZI as a Single Agent Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions. IMFINZI with IMJUDO Immune‑mediated hepatitis occurred in 7.5% (29/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.8%), Grade 4 (0.3%) and Grade 3 (4.1%) adverse reactions. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated hepatitis occurred in 3.9% (23/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.3%), Grade 4 (0.5%), and Grade 3 (2%) adverse reactions. Immune-Mediated Endocrinopathies Adrenal Insufficiency : IMFINZI and IMJUDO can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. IMFINZI as a Single Agent Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. IMFINZI with IMJUDO Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated adrenal insufficiency occurred in 2.2% (13/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.8%) adverse reactions. Hypophysitis : IMFINZI and IMJUDO can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated. IMFINZI as a Single Agent Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received IMFINZI. IMFINZI with IMJUDO Immune-mediated hypophysitis/hypopituitarism occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated hypophysitis occurred in 1.3% (8/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions. Thyroid Disorders (Thyroiditis, Hyperthyroidism, and Hypothyroidism) : IMFINZI and IMJUDO can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. IMFINZI as a Single Agent Immune-mediated thyroiditis occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of patients receiving IMFINZI. Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. IMFINZI with IMJUDO Immune-mediated thyroiditis occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO. Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions. Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving IMFINZI and IMJUDO. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated thyroiditis occurred in 1.2% (7/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy. Immune-mediated hyperthyroidism occurred in 5% (30/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions. Immune-mediated hypothyroidism occurred in 8.6% (51/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions. Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis : Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. IMFINZI as a Single Agent Grade 3 immune-mediated Type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI. IMFINZI with IMJUDO Two patients (0.5%, 2/388) had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated Type 1 diabetes mellitus occurred in 0.5% (3/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including Grade 3 (0.3%) adverse reactions. Immune-Mediated Nephritis with Renal Dysfunction IMFINZI and IMJUDO can cause immune-mediated nephritis. IMFINZI as a Single Agent Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. IMFINZI with IMJUDO Immune-mediated nephritis occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.5%) adverse reactions. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated nephritis occurred in 0.7% (4/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions. Immune-Mediated Dermatology Reactions IMFINZI and IMJUDO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 and CTLA-4 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. IMFINZI as a Single Agent Immune-mediated rash or dermatitis occurred in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions. IMFINZI with IMJUDO Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated rash or dermatitis occurred in 7.2% (43/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions. Immune-Mediated Pancreatitis IMFINZI in combination with IMJUDO can cause immune-mediated pancreatitis. Immune-mediated pancreatitis occurred in 2.3% (9/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions. Other Immune-Mediated Adverse Reactions The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI and IMJUDO or were reported with the use of other immune-checkpoint inhibitors. Cardiac/vascular : Myocarditis, pericarditis, vasculitis. Nervous system : Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy. Ocular : Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss. Gastrointestinal : Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis. Musculoskeletal and connective tissue disorders : Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic. Endocrine : Hypoparathyroidism. Other (hematologic/immune) : Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection. Infusion-Related Reactions IMFINZI and IMJUDO can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI and IMJUDO based on the severity. See USPI Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. IMFINZI as a Single Agent Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions. IMFINZI with IMJUDO Infusion-related reactions occurred in 10 (2.6%) patients receiving IMFINZI and IMJUDO. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Infusion-related reactions occurred in 2.9% (17/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions. Complications of Allogeneic HSCT after IMFINZI Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT. Embryo-Fetal Toxicity Based on their mechanism of action and data from animal studies, IMFINZI and IMJUDO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. In females of reproductive potential, verify pregnancy status prior to initiating IMFINZI and IMJUDO and advise them to use effective contraception during treatment with IMFINZI and IMJUDO and for 3 months after the last dose of IMFINZI and IMJUDO. Lactation There is no information regarding the presence of IMFINZI and IMJUDO in human milk; however, because of the potential for serious adverse reactions in breastfed infants from IMFINZI and IMJUDO, advise women not to breastfeed during treatment and for 3 months after the last dose. Adverse Reactions In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), the most common adverse reactions (≥20%) were cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis (34%), upper respiratory tract infections (26%), dyspnea (25%), and rash (23%). The most common Grade 3 or 4 adverse reactions (≥3%) were pneumonia (7%) and pneumonitis/radiation pneumonitis (3.4%). In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), discontinuation due to adverse reactions occurred in 15% of patients in the IMFINZI arm. Serious adverse reactions occurred in 29% of patients receiving IMFINZI. The most frequent serious adverse reactions (≥2%) were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation pneumonitis and fatal pneumonia occurred in <2% of patients and were similar across arms. In patients with mNSCLC in the POSEIDON study receiving IMFINZI and IMJUDO plus platinum-based chemotherapy (n=330), the most common adverse reactions (occurring in ≥20% of patients) were nausea (42%), fatigue (36%), musculoskeletal pain (29%), decreased appetite (28%), rash (27%), and diarrhea (22%). In patients with mNSCLC in the POSEIDON study receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy (n=330), permanent discontinuation of IMFINZI or IMJUDO due to an adverse reaction occurred in 17% of patients. Serious adverse reactions occurred in 44% of patients, with the most frequent serious adverse reactions reported in at least 2% of patients being pneumonia (11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%), pyrexia (2.4%), and febrile neutropenia (2.1%). Fatal adverse reactions occurred in a total of 4.2% of patients. In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), the most common adverse reactions (≥20%) were nausea (34%), fatigue/asthenia (32%), and alopecia (31%). The most common Grade 3 or 4 adverse reaction (≥3%) was fatigue/asthenia (3.4%). In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), IMFINZI was discontinued due to adverse reactions in 7% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 31% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and COPD (1.1%). Fatal adverse reactions occurred in 4.9% of patients receiving IMFINZI plus chemotherapy. In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), the most common adverse reactions (occurring in ≥20% of patients) were fatigue (42%), nausea (40%), constipation (32%), decreased appetite (26%), abdominal pain (24%), rash (23%), and pyrexia (20%). In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), discontinuation due to adverse reactions occurred in 6% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 47% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 2% of patients were cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%) and acute kidney injury (2.4%). Fatal adverse reactions occurred in 3.6% of patients receiving IMFINZI plus chemotherapy. These include ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients), and upper gastrointestinal hemorrhage (2 patients). In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), the most common adverse reactions (occurring in ≥20% of patients) were rash (32%), diarrhea (27%), fatigue (26%), pruritus (23%), musculoskeletal pain (22%), and abdominal pain (20%). In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), serious adverse reactions occurred in 41% of patients. Serious adverse reactions in >1% of patients included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%). Fatal adverse reactions occurred in 8% of patients who received IMJUDO in combination with durvalumab, including death (1%), hemorrhage intracranial (0.5%), cardiac arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and immune-mediated hepatitis (0.5%). Permanent discontinuation of treatment regimen due to an adverse reaction occurred in 14% of patients. The safety and effectiveness of IMFINZI and IMJUDO have not been established in pediatric patients. Indications : IMFINZI is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) genomic tumor aberrations. IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC). IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). Please see Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO . Notes Advanced non-small cell lung cancer Nearly 2.5 million lung cancer cases were diagnosed globally in 2022. 1 NSCLC is the most common type of lung cancer, accounting for about 80% of cases. 2 Approximately 75% and 25% of NSCLC tumors are of nonsquamous or squamous histology, respectively. 3 While immunotherapy and targeted therapies have improved outcomes in the 1st-line metastatic setting, most patients eventually experience disease progression and receive chemotherapy. 4-6 For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC, despite limited effectiveness and known side effects. 4-6 TROP2 is a protein broadly expressed in the majority of NSCLC tumors. 7 There is currently no TROP2-directed ADC approved for the treatment of lung cancer. 8,9 TROPION-Lung01 TROPION-Lung01 is a global, randomized, multicenter, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0mg/kg) versus docetaxel (75mg/m 2 ) in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. Patients with actionable genomic alterations were previously treated with platinum-based chemotherapy and an approved targeted therapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. The dual primary endpoints of TROPION-Lung01 are PFS as assessed by blinded independent central review (BICR) and OS. Key secondary endpoints include investigator-assessed PFS, objective response rate (ORR), duration of response, time to response, disease control rate as assessed by both BICR and investigator, and safety. TROPION-Lung01 enrolled approximately 600 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov. NeoCOAST-2 NeoCOAST-2 is a global, randomized, multicenter, open-label, multi-arm Phase II platform trial evaluating the efficacy and safety of IMFINZI ® (durvalumab) in multiple novel combinations, before and after surgery, in patients with resectable, early-stage (Stage II-IIIB) NSCLC. The dual primary endpoints of NeoCOAST-2 are antitumor activity of neoadjuvant treatment assessed by pCR and the safety and tolerability of neoadjuvant and adjuvant treatment. Key secondary endpoints include event-free survival, disease-free survival and ORR as assessed by both RECIST version 1.1 and investigator, OS, tumor resection and mPR as defined by central blinded independent pathologist review. NeoCOAST-2 will enroll approximately 490 patients in Asia, Europe and North America. For more information visit ClinicalTrials.gov . Datopotamab deruxtecan (Dato-DXd) Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer and HR-positive, HER2-negative breast cancer. The program includes seven Phase III trials in lung cancer and five Phase III trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings. Daiichi Sankyo collaboration AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialize fam-trastuzumab deruxtecan-nxki in March 2019 and datopotamab deruxtecan in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan. AstraZeneca in lung cancer AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most. The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including osimertinib and gefitinib; IMFINZI and tremelimumab-actl; fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan in collaboration with Daiichi Sankyo; savolitinib in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action. AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. About AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow the us on social media @AstraZeneca. References World Health Organization. Global Cancer Observatory: Lung. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf . Accessed September 2024. Cancer.net. Lung Cancer – Non-Small Cell: Statistics. Available at: https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics#:~:text=NSCLC%20is%20the%20most%20common,be%20diagnosed%20with%20lung%20cancer . Accessed September 2024. National Cancer Institute. SEER Cancer Statistics Factsheets: Lung and Bronchus Cancer. Available at: https://seer.cancer.gov/archive/csr/1975_2017/results_merged/sect_15_lung_bronchus.pdf . Accessed September 2024. Chen R, et al . 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