Rilvegostomig

The first patient has been dosed in the TROPION-Urothelial04 phase 3 trial evaluating Datroway® (datopotamab deruxtecan) plus rilvegostomig or Datroway monotherapy versus current standard of care (durvalumab monotherapy or nivolumab monotherapy or enfortumab vedotin plus pembrolizumab) as an adjuvant treatment (after surgery) in patients with muscle invasive urothelial cancer (MIUC) at high risk of recurrence following radical surgical resection with or without prior neoadjuvant therapy. Datroway is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/NYSE: AZN). Rilvegostomig is AstraZeneca’s anti-PD-1/TIGIT dual checkpoint inhibitor bispecific antibody. MIUC is a highly progressive disease, representing approximately 30% of all urothelial cancer cases.1,2 While adjuvant immunotherapy remains standard of care in the muscle invasive setting, many patients still face a high risk for disease recurrence after surgery, underscoring the need for new treatments that can further improve long-term outcomes.3 There are currently no TROP2 directed medicines approved for the treatment of urothelial cancer. “Following the encouraging results in the urothelial cancer cohorts of the TROPION-PanTumor03 and TROPION-PanTumor01 trials, we are now evaluating the combination of Datroway and rilvegostomig in earlier lines of treatment for this disease,” said Abderrahmane Laadem, MD, Head, Therapeutic Area Oncology Development, Daiichi Sankyo. “TROPION-Urothelial04 marks our second pivotal trial in urothelial cancer as we continue to identify different types of cancer where Datroway may contribute to improving outcomes for patients.” “Patients with muscle invasive urothelial cancer continue to face a significant risk of disease recurrence despite recent new advances,” said Leora Horn, MD, FRCPC, Senior Vice President, Late Development Oncology, AstraZeneca. “TROPION-Urothelial04 will allow us to further evaluate the potential of Datroway in combination with rilvegostomig to help advance treatment approaches and move closer to a cure for these patients with significant unmet need.” Daiichi Sankyo and AstraZeneca also are evaluating Datroway plus platinum-based chemotherapy compared to gemcitabine and platinum-based chemotherapy in patients with metastatic urothelial carcinoma following progression during or after treatment with enfortumab vedotin in combination with pembrolizumab in the TROPION-Urothelial03 phase 2/3 trial. TROPION-Urothelial04 is a global, multicenter, three-arm open-label phase 3 trial where patients will be randomized in a 2:1:2 ratio to evaluate the efficacy and safety of Datroway in combination with rilvegostomig or Datroway monotherapy versus current standard of care (durvalumab monotherapy or nivolumab monotherapy or enfortumab vedotin plus pembrolizumab) in patients with high-risk MIUC, including those with residual disease at surgical resection following neoadjuvant therapy and those with high-risk disease after surgery without neoadjuvant therapy. The primary endpoint of TROPION-Urothelial04 is disease free survival (DFS) as assessed by investigator for the combination of Datroway and rilvegostomig versus standard of care. Key secondary endpoints include DFS as assessed by blinded independent central review, disease specific survival, non-urothelial tract recurrence-free survival, distant metastasis-free survival, patient reported outcomes, overall survival and safety. TROPION-Urothelial04 will enroll approximately 915 patients across multiple sites in Asia, Europe, North America, Oceania and South America.. The TIGIT component of rilvegostomig is derived from the clinical-stage anti-TIGIT antibody, COM902, developed by Compugen Ltd. (Nasdaq/TASE: CGEN). The most common type of bladder cancer is urothelial cancer, accounting for approximately 90% of cases.4 Urothelial cancer can originate in the upper urinary tract (renal pelvis, ureter) or the lower urinary tract (bladder, urethra).5 Muscle invasive urothelial cancer is a highly progressive disease, which occurs when the cancer has spread to the muscle walls of the bladder and represents approximately 30% of all urothelial cancer cases.1,2,6 More than 635,000 bladder cancer cases were diagnosed globally in 2024, and while the five-year survival rate for localized urothelial and bladder cancer is more than 70%, survival decreases to approximately 9% in the metastatic setting.6,7,8 While adjuvant immunotherapy remains standard of care in the muscle invasive setting, many patients still face a high risk for disease recurrence after surgery, underscoring the need for new treatments that can further improve long-term outcomes.3 TROP2 is a protein broadly expressed in several solid tumors including urothelial cancer.9 TROP2 expression is positively correlated with disease severity in patients with urothelial cancer.10 Datroway (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the U.S. only) is a TROP2 directed ADC. Designed using the proprietary DXd ADC Technology of Daiichi Sankyo, Datroway is one of seven DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datroway 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. Datroway (6 mg/kg) is approved in more than 30 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic triple negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy based on the results from the TROPION-Breast02 trial. Datroway (6 mg/kg) is approved in more than 45 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on the results from the TROPION-Breast01 trial. Datroway (6 mg/kg) is approved in Brazil, Russia, Singapore and the U.S. for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy based on the results from TROPION-Lung05 and TROPION-Lung01 trials. Continued approval for this indication in the U.S. may be contingent upon verification and description of clinical benefit in a confirmatory trial. A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of Datroway across multiple cancers, including NSCLC, TNBC and urothelial cancer. The program includes eight phase 3 trials in lung cancer, five phase 3 trials in breast cancer, one phase 3 trial and one phase 2/3 trial in urothelial cancer evaluating Datroway as a monotherapy and in combination with other cancer treatments in various settings. Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize Enhertu® in March 2019 and Datroway 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 Datroway. The content above comes from the network. if any infringement, please contact us to modify.