On Target Laboratories LLC

CYTALUX is now approved as the first and only targeted molecular imaging agent that illuminates lung cancer intraoperatively, enabling the detection of more cancer for removal. CYTALUX is also the first and only targeted molecular imaging agent that illuminates ovarian cancer in real-time during surgery. WEST LAFAYETTE, Ind., Dec. 16, 2022 /PRNewswire/ -- On Target Laboratories, Inc., a privately-held biotechnology company developing intraoperative molecular imaging agents to target and illuminate cancer during surgery, today announced that the U.S. Food and Drug Administration (FDA) has approved an expanded indication for the use of CYTALUX in lung cancer. CYTALUX is the first and only targeted molecular imaging agent that illuminates lung and ovarian cancer intraoperatively, enabling the detection of more cancer for removal. The new indication will provide surgeons the ability to integrate CYTALUX into their treatment plan for adult patients with known or suspected lung cancer, where it previously was only approved for adults with ovarian cancer. Continue Reading On Target Lung Cancer Indication Media Kit (Video) CYTALUX illuminating cancer in lungs Experience the full interactive Multichannel News Release here: The label expansion is based on safety and efficacy evidence demonstrated in the ELUCIDATE Trial, a Phase 3, multi-center, single dose, open-label trial that investigated the use of CYTALUX in patients scheduled to undergo thoracic surgery for confirmed or suspected lung cancer. Lung cancer is the leading cause of cancer deaths, with over 130,000 deaths from the disease in the U.S.1 and nearly 1.8 million globally2 each year. While surgery is a gold-standard treatment, up to 55% of people with lung cancer who undergo surgery with curative intent have a recurrence3. During surgery for lung cancer, some lesions can be difficult for surgeons to visualize, particularly if they are small, beneath the surface of the lung, or a type of lesion called a ground glass opacity, which is becoming increasingly common as the rates of lung cancer screenings rise. "Today's approval of an expanded indication for CYTALUX marks an important step forward in the treatment landscape for lung cancer and for the more than 220,000 people in the U.S. who receive a lung cancer diagnosis each year," said Chris Barys, President and Chief Executive Officer of On Target Laboratories, Inc. "We are proud to continue pioneering development of targeted intraoperative molecular imaging agents that illuminate cancers intraoperatively to enhance surgeons' ability to see cancer in real time as they operate." "During the ELUCIDATE Trial, CYTALUX proved to be a valuable surgical tool with its ability to localize lung lesions that may have otherwise been missed," said Dr. Linda Martin, Chief of Thoracic Surgery, University of Virginia School of Medicine. "CYTALUX has potential to become standard of care in thoracic surgery because of the safety and efficacy demonstrated in the trial. It is an important tool for surgeons to consider for patients." CYTALUX was approved in November 2021 for use in adult patients with ovarian cancer as an adjunct for intraoperative identification of malignant lesions. CYTALUX is the first targeted molecular imaging agent that illuminates ovarian and lung cancer intraoperatively, enabling the detection of more cancer for removal. CYTALUX, administered by standard IV in as little as one hour before surgery, binds to folate receptors that are overexpressed in certain cancers4,5 and illuminates intraoperatively under near-infrared light. About the ELUCIDATE Trial The ELUCIDATE ( Enabling LUng Cancer IDentification Using Fol ATE Receptor Targeting) trial was a Phase 3, multi-center, single dose, open label trial led by Principal Investigator, Sunil Singhal, MD, the William Maul Measey Professor in Surgical Research and director of the Center for Precision Surgery at Penn Medicine and included 12 sites across the United States. The study (NCT04241315) investigated the use of CYTALUX (pafolacianine) injection in patients scheduled to undergo thoracic surgery for confirmed or suspected lung cancer. About Intraoperative Molecular Imaging To date, there have been limited ways for surgeons to confidently assess the location and full extent of cancerous tissue while operating. Intraoperative Molecular Imaging (IMI) is an emerging category of technology for surgical oncology in which targeted imaging agents are injected into patients to highlight cancer cells making them visible during surgery. About On Target Laboratories, Inc. On Target Laboratories discovers and develops targeted intraoperative molecular imaging agents to illuminate cancer during surgery. Their molecular imaging technology, based on the pioneering work of Philip S. Low, PhD, Purdue University's Presidential Scholar for Drug Discovery and the Ralph C. Corley Distinguished Professor of Chemistry, is comprised of a near-infrared dye and a targeting molecule, or ligand, that binds to receptors overexpressed on cancer cells. The imaging agents illuminate the cancerous tissue, which may enable surgeons to detect more cancer that otherwise may have been left behind. CYTALUX, the Company's first product, received FDA approval for ovarian cancer in November 2021 and lung cancer in December 2022. CYTALUX targets the folate receptors commonly found on many cancers, binds to the cancerous tissue, and illuminates under near-infrared light. A single dose of the agent is administered via intravenous infusion prior to surgery and assists surgeons in visually identifying additional malignant tissue to be removed during the operation. For more information visit and . What is CYTALUX? CYTALUX is an FDA approved prescription medication that is given prior to surgery to adult patients who have ovarian cancer or known or suspected cancer in the lung. It helps surgeons visualize ovarian and lung cancer lesions during surgery. Important Safety Information Infusion-Related Reactions Adverse reactions including nausea, vomiting, abdominal pain, flushing, allergic reaction, elevation in blood pressure, indigestion, and chest discomfort were reported during the administration of CYTALUX. Your doctor may treat you with antihistamines and/or anti-nausea medication. Risk of Misinterpretation Errors may occur with the use of CYTALUX. Sometimes cells may light up even if they are not cancerous or those that are cancerous may not light up. Also, non-cancerous cells from other areas may light up, such as areas of the bowel, kidneys, lymph nodes, lungs, and inflamed tissue. Pregnancy CYTALUX may cause fetal harm when administered to a pregnant woman. There are no available human data to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Contact your healthcare provider with a known or suspected pregnancy. Folate Supplementation Usage Folic acid may reduce the detection of cancerous tissue with CYTALUX. Patients should stop taking folate, folic acid, or folate-containing supplements 48 hours before administration of CYTALUX. Adverse Reactions The most common side effects of CYTALUX reported in clinical trials were nausea (13%), vomiting (5%), abdominal pain (2%), flushing (2%), other infusion-related reactions (2%), allergic reaction (2%), elevation in blood pressure (1%), indigestion (1%), and chest discomfort (1%) during administration. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of CYTALUX. For more information, ask your healthcare provider. Call your doctor for medical advice about side effects. You may report side effects to On Target Laboratories at 1-844-434-9333 or FDA at 1-800-FDA-1088 or . See full Prescribing Information for more details. Media Contacts On Target Laboratories, Inc. Jessica Todd Phone: 513-325-5706 [email protected] Syneos Health Danielle Kirsch Phone: 201-693-3197 [email protected] References NIH National Cancer Institute. Cancer Stat Facts: Lung and Bronchus Cancer. Accessed December 2022. World Health Organization. International Agency for Research on Cancer Global Cancer Observatory. Accessed May 2022. Uramoto H, Tanaka F. Recurrence after surgery in patients with NSCLC. Transl Lung Cancer Res. 2014 Aug;3(4):242-9. doi: 10.3978/j.issn.2218-6751.2013.12.05. PMID: 25806307; PMCID: PMC4367696. Predina JD, Newton AD, Connolly C, Dunbar A, Baldassari M, Deshpande C, Cantu E 3rd, Stadanlick J, Kularatne SA, Low PS, Singhal S. Identification of a Folate Receptor-Targeted Near-Infrared Molecular Contrast Agent to Localize Pulmonary Adenocarcinomas. Mol Ther. 2018 Feb 7;26(2):390-403. doi: 10.1016/j.ymthe.2017.10.016. Epub 2017 Oct 26. PMID: 29241970; PMCID: PMC5835020. Kalli KR, Oberg AL, Keeney GL, et al. Folate receptor alpha as a tumor target in epithelial ovarian cancer. Gynecologic Oncology. 2008;108(3):619-626. SOURCE On Target Laboratories, Inc.

WEST LAFAYETTE, Ind., Sept. 12, 2022 /PRNewswire/ -- On Target Laboratories, Inc., a privately-held biotechnology company developing intraoperative molecular imaging agents to target and illuminate cancer during surgery, today announced publication of results from the Phase 3 006 Study of CYTALUX (pafolacianine) injection for intraoperative imaging of folate receptor positive ovarian cancer in the peer-reviewed Journal of Clinical Oncology. The research article reports that use of CYTALUX during ovarian cancer surgery demonstrated identification of additional ovarian cancer that was not identified with conventional means and not otherwise planned for resection. 150 patients in the safety analysis set received a single infusion of CYTALUX, resulting in 109 patients with folate receptor positive ovarian cancer comprising the full analysis set for efficacy. In 33% of patients*, near-infrared imaging with CYTALUX identified additional lesions which would have been left behind (P < 0.001, 95% CI [0.243, 0.427]). The rate was higher, at 39.7%, among patients who underwent interval debulking surgery (95% CI [0.270, 0.534]). "This pivotal study indicates that CYTALUX may offer an important real-time adjunct to current surgical approaches for ovarian cancer," said Chris Barys, President and Chief Executive Officer of On Target. "We are grateful to the study participants and investigators for their important role in this research and are committed to continuing to pioneer the use and study of intraoperative molecular imaging to increase detection of malignant lesions during surgery." "There are many limitations to current operative approaches of visual inspection and palpation, and I am encouraged that, in this clinical trial, near-infrared imaging with CYTALUX identified additional lesions in 33% of participants which would have been left behind," said Janos L. Tanyi, MD, PhD, an associate professor of Obstetrics and Gynecology in the Perelman School of Medicine at the University of Pennsylvania and principal investigator of the Phase 3 trial. "These results further the evidence that intraoperative molecular imaging may help surgeons achieve complete surgical resection of cancer." * N=36 out of 109 folate receptor positive ovarian cancer patients. CYTALUX USPI describes the proportion of patients in which CYTALUX identified additional lesions in the "intent-to-image set" regardless of ovarian cancer status (N=36 out of 134, 27%) About On Target Laboratories, Inc. On Target Laboratories discovers and develops targeted intraoperative molecular imaging agents to illuminate cancer during surgery. Their molecular imaging technology, based on the pioneering work of Philip S. Low, PhD, Purdue University's Presidential Scholar for Drug Discovery and the Ralph C. Corley Distinguished Professor of Chemistry, are comprised of a near-infrared dye and a targeting molecule, or ligand, that binds to receptors overexpressed on cancer cells. The imaging agents illuminate the cancerous tissue, which may enable surgeons to detect more cancer that otherwise may have been left behind. CYTALUX, the Company's first product, received FDA approval for ovarian cancer in November 2021. CYTALUX targets folate receptors commonly found on many cancers, such as ovarian cancer. A single dose of the agent is administered via intravenous infusion prior to surgery to help the surgeon identify additional malignant tissue during the operation using a near-infrared imaging system. For more information visit and . CYTALUX Indication CYTALUX is an FDA-approved optical imaging agent indicated in adult patients with ovarian cancer as an adjunct for intraoperative identification of malignant lesions. Important Safety Information Infusion-Related Reactions Adverse reactions consisting of nausea, vomiting, abdominal pain, flushing, indigestion, chest discomfort, and itching were reported during the administration of CYTALUX. Your doctor may treat you with antihistamines and/or anti-nausea medication. Pregnancy CYTALUX may cause fetal harm when administered to a pregnant woman. There are no available human data to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Contact your healthcare provider with a known or suspected pregnancy. Folate Supplement Usage Folic acid may reduce the detection of cancerous tissue with CYTALUX. Patients should stop taking folate, folic acid, or folate-containing supplements 48 hours before administration of CYTALUX. Risk of Misinterpretation Errors may occur with the use of CYTALUX. Sometimes cells may light up even if they are not cancerous or those that are cancerous may not light up. Also, cancerous or non-cancerous cells from other areas may light up, such as areas of the bowel, kidneys, lymph nodes, and inflamed tissue. Adverse Reactions The most common side effects of CYTALUX reported in clinical trials were nausea, vomiting, abdominal pain, flushing, indigestion, chest discomfort, itching, and allergic reaction during administration or infusion. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of CYTALUX. For more information, ask your healthcare provider. Call your doctor for medical advice about side effects. You may report side effects to On Target Laboratories at 1-844-434-9333 or FDA at 1-800-FDA-1088 or . Click here to see full Prescribing Information SOURCE On Target Laboratories, Inc.

Aug. 16, 2022 11:00 UTC First PARP inhibitor to demonstrate clinical benefit in combination with a new hormonal agent irrespective of homologous recombination repair (HRR) gene mutations WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca’s supplemental New Drug Application (sNDA) for LYNPARZA® (olaparib) in combination with abiraterone and prednisone or prednisolone has been accepted and granted Priority Review in the US for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC). LYNPARZA is being jointly developed and commercialized by AstraZeneca and Merck & Co., Inc., known as MSD outside the US and Canada. The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that offer significant advantages over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance.1 The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is anticipated during the fourth quarter of 2022. In the US, prostate cancer is the second most common cancer in male patients and is projected to cause approximately 35,000 deaths in 2022.2 Overall survival for patients with mCRPC is approximately three years in clinical trial settings, and even shorter in the real world.3-6 Approximately half of patients with mCRPC may receive only one line of active treatment, with diminishing benefit of subsequent therapies.6-11 Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “There remains a critical unmet need among patients diagnosed with metastatic castration-resistant prostate cancer, where the prognosis remains poor and treatment options are limited. Today’s news is another step towards bringing forward a new, much needed treatment option in this setting. If approved, LYNPARZA with abiraterone will become the first combination of a PARP inhibitor and a new hormonal agent for patients with this disease.” Dr. Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories, said: “Merck is committed to developing new treatment options for patients with metastatic castration-resistant prostate cancer, a complex disease that urgently needs more therapies. We look forward to working with the FDA towards the goal of bringing a new option to patients with mCRPC with or without HRR gene mutations.” The sNDA was based on results from the PROpel Phase III trial presented at the 2022 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium and later published in NEJM Evidence. These results showed LYNPARZA in combination with abiraterone reduced the risk of disease progression or death by 34% versus abiraterone alone (based on a hazard ratio [HR] of 0.66; 95% confidence interval [CI] 0.54-0.81; p<0.0001). Median radiographic progression-free survival (rPFS) was 24.8 months for LYNPARZA plus abiraterone versus 16.6 for abiraterone alone. The safety and tolerability of LYNPARZA in combination with abiraterone was in line with that observed in prior clinical trials and the known profiles of the individual medicines.12 LYNPARZA is approved in the US for patients with HRR gene-mutated mCRPC (BRCA-mutated and other HRR gene mutations) who have progressed following prior treatment with enzalutamide or abiraterone; and in the EU, Japan and China for patients with BRCA-mutated mCRPC who have progressed following prior therapy that included a new hormonal agent. These approvals were based on the data from the PROfound Phase III trial. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS There are no contraindications for LYNPARZA. WARNINGS AND PRECAUTIONS Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately 1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The median duration of therapy in patients who developed MDS/AML was 2 years (range: <6 months to >10 years). All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy. Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed. Pneumonitis: Occurred in 0.8% of patients exposed to LYNPARZA monotherapy, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately. Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment. Females Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose. Males Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time. Venous Thromboembolic Events: Including pulmonary embolism, occurred in 7% of patients with metastatic castration-resistant prostate cancer who received LYNPARZA plus androgen deprivation therapy (ADT) compared to 3.1% of patients receiving enzalutamide or abiraterone plus ADT in the PROfound study. Patients receiving LYNPARZA and ADT had a 6% incidence of pulmonary embolism compared to 0.8% of patients treated with ADT plus either enzalutamide or abiraterone. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated. ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), urinary tract infection (13%), thrombocytopenia (11%), and stomatitis (11%). Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%). ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab Most common adverse reactions (Grades 1-4) in ≥10% of patients treated with LYNPARZA/bevacizumab compared to a ≥5% frequency for placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%), and leukopenia (18%). In addition, the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%), and headache (14%). In addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%). Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%), and decrease in platelets (35%). ADVERSE REACTIONS—Maintenance Recurrent Ovarian Cancer Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%). Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), decreased appetite (21%), and dyspepsia (20%). Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%). ADVERSE REACTIONS—Advanced gBRCAm Ovarian Cancer After 3 or More Lines of Chemotherapy Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue/asthenia (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%). Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA for advanced gBRCAm ovarian cancer (pooled from 6 studies) were: decrease in hemoglobin (90%), mean corpuscular volume elevation (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%). ADVERSE REACTIONS—Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: nausea (57%), fatigue (including asthenia) (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%), and stomatitis (10%). Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: decrease in lymphocytes (77%), increase in mean corpuscular volume (67%), decrease in hemoglobin (65%), decrease in leukocytes (64%), and decrease in absolute neutrophil count (39%). ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast Cancer Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%). Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%). ADVERSE REACTIONS—First-Line Maintenance gBRCAm Metastatic Pancreatic Adenocarcinoma Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: fatigue (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%). Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: increase in serum creatinine (99%), decrease in hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease in platelets (56%), decrease in leukocytes (50%), and decrease in absolute neutrophil count (25%). ADVERSE REACTIONS—HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA for PROfound were: anemia (46%), fatigue (including asthenia) (41%), nausea (41%), decreased appetite (30%), diarrhea (21%), vomiting (18%), thrombocytopenia (12%), cough (11%), and dyspnea (10%). Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA for PROfound were: decrease in hemoglobin (98%), decrease in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%). DRUG INTERACTIONS Anticancer Agents: Clinical studies of LYNPARZA with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity. CYP3A Inhibitors: Avoid coadministration of strong or moderate CYP3A inhibitors when using LYNPARZA. If a strong or moderate CYP3A inhibitor must be coadministered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment. CYP3A Inducers: Avoid coadministration of strong or moderate CYP3A inducers when using LYNPARZA. USE IN SPECIFIC POPULATIONS Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose. Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients. Hepatic Impairment: No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C). Renal Impairment: No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min). INDICATIONS LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated: First-Line Maintenance BRCAm Advanced Ovarian Cancer For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA. First-Line Maintenance HRD-Positive Advanced Ovarian Cancer in Combination with Bevacizumab In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either: a deleterious or suspected deleterious BRCA mutation, and/or genomic instability Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA. Maintenance Recurrent Ovarian Cancer For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy. Advanced gBRCAm Ovarian Cancer For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA. Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer For the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA. gBRCAm, HER2-Negative Metastatic Breast Cancer For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA. First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA. HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA. Please see complete Prescribing Information, including Medication Guide. Notes Metastatic castration-resistant prostate cancer Metastatic prostate cancer is associated with a significant mortality rate.13 Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone.14 In patients with mCRPC, their prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones.7 Approximately 10-20% of men with advanced prostate cancer will develop castration-resistant prostate cancer (CRPC) within five years, and at least 84% of these men will have metastases at the time of CRPC diagnosis.7 Of patients with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.6 Despite the advances in mCRPC treatment in the past decade with taxane and new hormonal agent (NHA) treatment, there is high unmet need in this population.7,9,10,15 PROpel PROpel is a randomized, double-blind, multi-center Phase III trial testing the efficacy, safety, and tolerability of LYNPARZA versus placebo when given in addition to abiraterone in men with mCRPC who had not received prior chemotherapy or NHAs in the mCRPC setting. Men in both treatment groups will also receive either prednisone or prednisolone twice daily. The primary endpoint is rPFS and secondary endpoints include overall survival, time to secondary progression or death, and time to first subsequent therapy. For more information about the trial please visit ClinicalTrials.gov. LYNPARZA LYNPARZA (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumors harboring a deficiency in HRR, such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as NHAs). Inhibition of PARP with LYNPARZA leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. In the PROpel Phase III trial, LYNPARZA is combined with abiraterone, an NHA which targets the androgen receptor (AR) pathway. Androgen receptor signaling engages a transcriptional program that is critical for tumor cell growth & survival in prostate cancer.16,17 Preclinical models have identified interactions between PARP signaling and the AR pathway which support the observation of a combined anti-tumor effect of LYNPARZA and NHAs, like abiraterone, in both HRR deficient and HRR proficient prostate cancer.18,19,20 The PARP1 protein has been reported to be required for the transcriptional activity of androgen receptors; therefore inhibiting PARP with LYNPARZA may impair the expression of androgen receptor target genes and enhance the activity of NHAs.16,19,21 Additionally, it is thought that abiraterone may alter/inhibit the transcription of some HRR genes which may induce HRR deficiency and increase sensitivity to PARP inhibition.18,20,22,23 LYNPARZA is currently approved in a number of countries across PARP-dependent tumor types with defects and dependencies in the DDR pathway including maintenance treatment of platinum-sensitive relapsed ovarian cancer and as both monotherapy and in combination with bevacizumab for the 1st-line maintenance treatment of BRCA-mutated (BRCAm) and homologous recombination repair deficient (HRD)-positive advanced ovarian cancer, respectively; for germline BRCAm (gBRCAm) HER2-negative metastatic breast cancer (in the EU and Japan this includes locally advanced breast cancer); for gBRCAm, HER2-negative high-risk early breast cancer; for gBRCAm metastatic pancreatic cancer; and HRR gene-mutated metastatic castration-resistant prostate cancer (BRCAm only in the EU and Japan). LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, is the foundation of AstraZeneca's industry-leading portfolio of potential new medicines. The AstraZeneca and Merck strategic oncology collaboration In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize LYNPARZA, the world’s first PARP inhibitor, and selumetinib, a mitogen-activated protein kinase (MEK) inhibitor, for multiple cancer types. Working together, the companies will develop LYNPARZA and selumetinib and other potential new medicines as monotherapies. The companies will also develop LYNPARZA and selumetinib in combination with their respective PD-L1 and PD-1 medicines independently. 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 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit and follow the Company on Twitter @AstraZenecaUS. References 1. US Food and Drug Administration. Priority Review. Available at: . Accessed August 2022. 2. Cancer.org. Key Statistics for Prostate Cancer. Available at . Accessed August 2022. 3. Ng K, et al. Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Advances and Treatment Strategies in the First-Line Setting. Oncol Ther. 2020; 8:209–230. 4. Shore N, et al. Real-World Treatment Patterns and Overall Survival of Patients with Metastatic Castration-Resistant Prostate Cancer in the US Prior to PARP Inhibitors. Adv Ther. 2021;38:4520–4540. 5. Wallis C, et al. Real-World Use of Androgen-Deprivation Therapy: Intensification Among Older Canadian Men With de Novo Metastatic Prostate Cancer. JNCI Cancer Spectrum. 2021;5(6):pkab082. 6. George D, et al. Treatment Patterns and Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer in a Real-world Clinical Practice Setting in the United States. Clinical Genitourinary Cancer. 2020 Aug;18(4):284-294. 7. Kirby, M, et al. Characterising the castration-resistant prostate cancer population: a systematic review. International Journal of Clinical Practice, 2021;65(11):1180-1192. 8. Smith MR, et al. Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol. 2005;23(13):2918-25. 9. UroToday. What is Changing in Advanced Prostate Cancer? Available at . Accessed August 2022. 10. Liu J, et al. Second-line Hormonal Therapy for the Management of Metastatic Castration-resistant Prostate Cancer: a Real-World Data Study Using a Claims Database. Scientific Report. 2020;10(4240):2020. 11. Mateo J, et al. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med. 2015; 373:1697-1708. 12. Clarke N, et al. Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer. NEJM. 2022;1(7) 13. Chowdhury S, et al. Real-world outcomes in first-line treatment of metastatic castration-resistant prostate cancer: the prostate cancer registry. Target Oncol. 2020;15(3):301-15. 14. Cancer.Net. Treatment of metastatic castration-resistant prostate cancer. Available at . Accessed August 2022. 15. UroToday. Beyond First-line Treatment of Metastatic Castrate-resistant Prostate Cancer. Available at Accessed August 2022. 16. Schiewer MJ, et al. Dual roles of PARP-1 promote cancer growth and progression. Cancer Discov. 2012;2(12):1134-1149. 17. Schiewer MJ & Knudsen KE. AMPed up to treat prostate cancer: novel AMPK activators emerge for cancer therapy. EMBO Mol Med. 2014;6(4):439-441. 18. Li L, et al. Androgen receptor inhibitor–induced “BRCAness” and PARP inhibition are synthetically lethal for castration-resistant prostate cancer. Sci Signal. 2017; 10(480):eaam7479. 19. Polkinghorn WR, et al. Androgen receptor signaling regulates DNA repair in prostate cancers. Cancer Discov. 2013;3(11):1245-1253. 20. Asim M, et al. Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer. Nat Commun. 2017;374(8). 21. Ju B-G, et al. A topoisomerase IIbeta-mediated dsDNA break required for regulated transcription. Science. 2006;312(5781):1798-1802. 22. Goodwin JF, et al. A hormone-DNA repair circuit governs the response to genotoxic insult. Cancer Discov. 2013;3(11):1254-1271. 23. Tarish FL, et al. Castration radiosensitizes prostate cancer tissue by impairing DNA double-strand break repair. Sci Transl Med. 2015; 7(312):312re11. US-67592 Last Updated 08/22