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SHANGHAI, Jan. 16, 2025 /PRNewswire/ -- IMPACT Therapeutics ("IMPACT"), a biopharmaceutical company focusing on the discovery and development of targeted anti-cancer therapeutics based on synthetic lethality, is pleased to announce that Senaparib Capsules (派舒宁®）has received marketing authorization in China from National Medical Products Administration (NMPA) as monotherapy for the maintenance treatment of adult patients with advanced epithelial (FIGO Stages III and IV) high-grade ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy. Senaparib, discovered and developed by IMPACT, is a potent and novel PARP 1/2 inhibitor. Its distinctive molecular structure provides it with high in vitro and in vivo activity, exceptional target selectivity and wide safety window. The approval is based on FLAMES Study. The study is a randomized, double-blind, placebo-controlled, multicenter, phase III clinical study to evaluate the efficacy and safety of Senaparib as monotherapy for the maintenance treatment of patients with advanced ovarian cancer who had completed first-line chemotherapy and achieved either a complete response (CR) or partial response (PR). The results of FLAMES Study showed that Senaparib demonstrated significant improvement in median PFS compared to placebo (PFS not reached vs 13.6 months, HR 0.43, P < 0.0001), irrespective of BRCA status. Senaparib demonstrated a tolerable safety profile, with no noticeable safety issues. [1]The results also indicated that both HRD positive and HRD negative populations derived benefit from Senaparib maintenance therapy, highlighting the potential of Senaparib for broad clinical application. The results of this study will strongly support Senaparib as the Standard of Care for first-line maintenance therapy in patients with newly diagnosed ovarian cancer. The top-line results of the study were initially presented as a late breaking oral presentation at ESMO in 2023 and presented at CSCO 2024. On May 15, 2024, the internationally renowned medical journal Nature Medicine also published the results titled "Senaparib as first-line maintenance therapy in advanced ovarian cancer: a randomized phase 3 trial."[1] Ovarian cancer is one of the most common lethal female reproductive malignancies. According to GLOBOCAN 2020 data, the global incidence of ovarian cancer is amounted to 310,000 cases and mortality is amounted to 210,000. According to the latest national cancer statistics released by National Cancer Center in 2024, there were 61,100 new cases of ovarian cancer and 32,600 deaths in China in 2022, making it the most lethal gynecological tumor. Due to the insidious and non-specific early symptoms of ovarian cancer, about 80% of patients are already in advanced stage when they are diagnosed, and the 5-year survival rate is only 41.8%. [2]Although ovarian cancer may be resolved after initial platinum-containing chemotherapy, most patients inevitably face recurrence, and there remains a significant unmet clinical need for treatment in the ovarian cancer patient population. In recent years, PARP inhibitors are changing the therapeutic landscape of ovarian cancer, with maintenance therapy extending the duration of sustained remission after platinum-containing chemotherapy and delaying disease recurrence. In December 2023, IMPACT entered into a collaboration agreement with Zhongmei Huadong Pharmaceutical Co., Ltd, a subsidiary of Huadong Medicine Co., Ltd (SZ.000963) (collectively, "Huadong Medicine") for the commercialization of Senaparib. Under the collaboration agreement, Huadong Medicine receives exclusive promotion rights of Senaparib in mainland China. Huadong Medicine is deeply involved in the field of gynecological oncology. Senaparib and Huadong Medicine's approved mirvetuximab soravtansine-gynx (ELAHERE®) can provide solutions for ovarian cancer patients with different stages of the disease, sharing expert networks, research and clinical resources, promoting and developing together to form an effective and highly synergistic relationship. Dr. Sui Xiong Cai, Chief Executive Officer of IMPACT said: "It is our great pleasure to share with you the successful approval of Senaparib for the Chinese market, which is another strong proof of the excellence of IMPACT's in-house synthetic lethality R&D platform and the R&D execution team. Leveraging Huadong Medicine's extensive commercial experiences in promoting novel therapeutics, we hope that Senaparib will reach more ovarian cancer patients soon and bring new treatment options for first-line maintenance therapy in advanced ovarian cancer." About IMPACT Therapeutics IMPACT Therapeutics is a biopharmaceutical company dedicated to the discovery and development of targeted anti-cancer therapeutics based on synthetic lethality. IMPACT Therapeutics has assembled one of the most comprehensive DNA damage responses (DDR) global pipeline of novel drug candidates generated by in-house discovery efforts and is expanding to other novel synthetic lethality targets to broaden its pipeline. IMPACT's pipeline products include PARP inhibitor Senaparib (IMP4297), WEE1 inhibitor (IMP7068), ATR inhibitor (IMP9064), and PARP1 selective inhibitor (IMP1734, in collaboration with Eikon Therapeutics), as well as other novel DDR pathway inhibitors. The most advanced development program, PARP inhibitor Senaparib (IMP4297), has been in clinical Phase II/III studies globally, including China, in ovarian cancer, small cell lung cancer and other indications. The Phase III clinical study (FLAMES Study) of Senaparib for advanced ovarian cancer maintenance treatment following first-line therapy met primary endpoint, with best-in-class efficacy and safety profile. Based on the results of the FLAMES study, the National Medicines Products Administration (NMPA) has approved the new drug application for Senaparib. The Wee1 inhibitor IMP7068 and the ATR inhibitor IMP9064 have been investigated in Phase I clinical studies in several countries and regions around the world, including U.S. and China, and the recommended Phase II dose (RP2D) has been established. PARP1 selective inhibitor IMP1734 has obtained IND clearance from FDA and NMPA, as well as completed FPI in early 2024. For additional information, please visit IMPACT Therapeutics Contact: +86 21 6841 1121 [email protected] SOURCE IMPACT Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

87.5% of patients treated with LYNPARZA were alive at six years vs. 83.2% in the comparator arm First and only PARP inhibitor to improve survival in early breast cancer WILMINGTON, DE, USA I December 11, 2024 I Updated results from the OlympiA Phase III trial showed AstraZeneca and Merck & Co., Inc’s, known as MSD outside of the US and Canada, LYNPARZA ® (olaparib) demonstrated sustained, clinically meaningful improvements in overall survival (OS), invasive disease-free survival (IDFS) and distant disease-free survival (DDFS) at six years for patients with germline BRCA-mutated (gBRCAm) HER2-negative high-risk early breast cancer. These results were presented today at the San Antonio Breast Cancer Symposium 2024 (SABCS) (#GS1-09) and build on the positive primary results published in The New England Journal of Medicine . At a median follow-up of 6.1 years in eligible patients, who had completed local treatment and standard neoadjuvant or adjuvant chemotherapy, results showed LYNPARZA reduced the risk of death by 28% (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.56-0.93) versus placebo. In addition,87.5% of patients treated with LYNPARZA remained alive versus 83.2% of those on placebo. LYNPARZA also demonstrated sustained and clinically meaningful improvements in the primary and secondary endpoints of IDFS and DDFS. LYNPARZA reduced the risk of invasive breast cancer recurrence, second cancers or death by 35% (HR 0.65; 95% CI; 0.53-0.78) and reduced the risk of distant disease recurrence or death by 35% (HR 0.65; 95% CI; 0.53-0.81) versus placebo. The benefit with LYNPARZA was consistent across all key subgroups, including patients with high-risk, hormone-receptor-positive disease. Judy E. Garber, Chief of the Division of Cancer Genetics and Prevention at Dana-Farber Cancer Institute and co-principal investigator of the trial said: “These exciting long-term data from OlympiA confirm that adjuvant treatment with olaparib for one year continues to deliver clinically meaningful survival benefit for patients with germline BRCA-mutated high-risk HER2-negative early breast cancer even after six years, with benefit persisting in all subgroups and with toxicity and pregnancy data reassuring for this generally younger group. These data reinforce the importance of germline BRCA testing at the time of diagnosis, so we can identify all eligible patients who may benefit from treatment with olaparib as early as possible.” Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Two years ago, LYNPARZA became the first and only PARP inhibitor to demonstrate a survival benefit in germline BRCA-mutated, HER2-negative and high-risk early-stage breast cancer. To see this benefit continue at six years of follow-up is tremendous for patients and reinforces how LYNPARZA is continuing to transform the treatment of BRCA-mutated early-stage breast cancer.” Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories, said: “The durable long-term efficacy seen in the OlympiA study reinforces LYNPARZA as an important treatment option for those living with this truly challenging, very aggressive form of the disease.” Summary of results The safety and tolerability profile of LYNPARZA in this trial was in line with that observed in prior clinical trials and no new safety signals were identified with longer follow-up. No evidence of an increased risk of myelodysplastic syndrome or acute myeloid leukemia was observed compared to those on placebo. The OlympiA trial is coordinated by the Breast International Group (BIG) in partnership with NRG Oncology, the US National Cancer Institute (NCI), the Frontier Science & Technology Research Foundation (FSTRF), AstraZeneca and Merck & Co., Inc. 1 LYNPARZA is approved in the US, EU, Japan, and many other countries for the treatment of gBRCAm, HER2-negative high-risk early breast cancer. LYNPARZA is also approved in the US, EU, Japan, and many other countries for the treatment of patients with gBRCAm, HER2-negative metastatic breast cancer. In the EU, this indication also includes patients with locally advanced breast cancer. INDICATIONS LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated: First-Line Maintenance BRCA m Advanced Ovarian Cancer For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA -mutated (g BRCA m or s BRCA m) 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: Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA. Maintenance BRCA -mutated Recurrent Ovarian Cancer For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA -mutated (g BRCA m or s BRCA m) recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA. Adjuvant Treatment of g BRCA m, HER2-Negative, High-Risk Early Breast Cancer For the adjuvant treatment of adult patients with deleterious or suspected deleterious g BRCA m, 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. g BRCA m, HER2-Negative Metastatic Breast Cancer For the treatment of adult patients with deleterious or suspected deleterious g BRCA m, 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 g BRCA m Metastatic Pancreatic Cancer For the maintenance treatment of adult patients with deleterious or suspected deleterious g BRCA m 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. BRCA m Metastatic Castration-Resistant Prostate Cancer in Combination with Abiraterone and Prednisone or Prednisolone In combination with abiraterone and prednisone or prednisolone (abi/pred) for the treatment of adult patients with deleterious or suspected deleterious BRCA -mutated ( BRCA m) metastatic castration-resistant prostate cancer (mCRPC). Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA. Notes Early breast cancer Early breast cancer is defined as cancer confined to the breast with or without regional lymph node involvement, and the absence of distant metastatic disease. 2 In the US, the 5-year survival rate is 99.6% for localized breast cancer (only found in the breast area) and 86.7% for regional breast cancer (cancer that has spread outside the breast to nearby structures or lymph nodes). 3 Despite advancements in the treatment of early breast cancer, up to 30% of patients with high-risk clinical and/or pathologic features recur within the first few years and patients with gBRCA mutations are more likely to be diagnosed at a younger age than those without these mutations. 4,5 Breast cancer is one of the most biologically diverse tumor types with various factors fueling its development and progression. 6 The discovery of biomarkers in the development of breast cancer has greatly impacted scientific understanding of the disease. 7 OlympiA OlympiA is a phase III, double-blind, parallel group, placebo-controlled, multicenter trial evaluating the efficacy and safety of LYNPARZA tablets versus placebo as a 12-month adjuvant treatment for adult patients with gBRCAm HER2-negative early breast cancer, who have completed neoadjuvant or adjuvant chemotherapy. 1 The primary endpoint of the trial is invasive disease-free survival defined as time from randomization to date of first loco-regional or distant recurrence or new cancer or death from any cause. Key secondary endpoints include distant disease-free survival and overall survival, which is defined as time from randomization until documented evidence of first distant recurrence of breast cancer or death without distant recurrence. 1 Breast International Group (BIG) BIG is an international not-for-profit organization for academic breast cancer research groups from around the world, based in Brussels, Belgium. Founded by leading European opinion leaders in 1999, the organization aims to address fragmentation in breast cancer research and now represents a network of over 50 like-minded research groups affiliated with specialized hospitals, research centers and leading experts across approximately 70 countries on six continents. BIG’s research is supported in part by its philanthropy unit, known as BIG against breast cancer, which is used to interact with the general public and donors, and to raise funds for BIG’s purely academic breast cancer trials and research programs. Frontier Science & Technology Research Foundation (FSTRF) FSTRF is a non-profit, research organization which supports research networks, pharmaceutical companies and investigators to conduct scientifically meaningful high-quality clinical trials. The OlympiA trial involved research staff in the US and in the Affiliate office in Scotland. FSTRF works with scientists and technicians in more than 800 laboratories, universities and medical centers around the world to provide a comprehensive range of research services throughout the clinical trial process including design, analysis and reporting. Through its work, FSTRF aims to advance the application of statistical science and practice and data management techniques in science, healthcare and education. NRG Oncology NRG Oncology is a network group funded by the US National Cancer Institute (NCI), a part of the National Institutes of Health. NRG Oncology brings together the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG), and the Gynecologic Oncology Group (GOG), with the mission to improve the lives of cancer patients by conducting practice-changing multi-institutional clinical and translational research. NRG Oncology sponsored OlympiA in the US and collaborated with the other adult cancer clinical trials research groups funded by the NCI, Alliance, ECOG/ACRIN and the Southwest Oncology Group. The NCI and AstraZeneca are collaborating under a Cooperative Research and Development Agreement between the parties. BRCA BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role maintaining the genetic stability of cells. 8 When either of these genes is mutated or altered such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer and confer sensitivity to PARP inhibitors including LYNPARZA. 8-11 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 homologous recombination-related (HRR) genes, such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as new hormonal agents [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. LYNPARZA may also help enhance immunogenicity and increase the impact of anti-tumor immune responses. LYNPARZA is currently approved in a number of countries across multiple tumor types, 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 gBRCAm metastatic pancreatic cancer; in combination with abiraterone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) when chemotherapy is not clinically indicated (EU only) and forBRCAm mCRPC (US and Japan); as monotherapy for HRR gene-mutated mCRPC in patients who have progressed on prior NHA treatment (BRCAm only in the EU and Japan); and in combination with durvalumab following durvalumab plus chemotherapy as 1st-line treatment for advanced or recurrent endometrial cancer that is mismatch repair proficient (EU and Japan). In China, LYNPARZA is approved for the treatment of BRCA-mutated mCRPC as well as 1st-line maintenance treatment with bevacizumab for HRD-positive advanced ovarian cancer. LYNPARZA, whichis being jointly developed and commercialized by AstraZeneca and Merck & Co., Inc., known as MSD outside the US and Canada, has been used to treat over 140,000 patients worldwide. LYNPARZA has a broad clinical trial development program, and AstraZeneca and Merck & Co., Inc., are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types. LYNPARZA is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells. The AstraZeneca and Merck & Co., Inc., 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 in combination with other potential new medicines and as monotherapies. The companies will 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. 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 us on social media @AstraZeneca . References SOURCE: AstraZeneca

RAHWAY, N.J.--( BUSINESS WIRE )--AstraZeneca and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced long-term results from the OlympiA Phase 3 trial which showed LYNPARZA (olaparib) demonstrated sustained, clinically meaningful improvements in overall survival (OS), invasive disease-free survival (IDFS) and distant disease-free survival (DDFS) for people with germline BRCA-mutated (gBRCAm) HER2-negative high-risk early breast cancer. These results were presented today at the 2024 San Antonio Breast Cancer Symposium (#GS1-09) and were consistent with positive primary results published in The New England Journal of Medicine . Judy E. Garber, Chief of the Division of Cancer Genetics and Prevention at Dana-Farber Cancer Institute and co-principal investigator of the trial said, “ These exciting long-term data from OlympiA confirm that adjuvant treatment with olaparib for one year continues to deliver clinically meaningful survival benefit for patients with germline BRCA-mutated high-risk HER2-negative early breast cancer even after six years, with benefit persisting in all subgroups and with toxicity and pregnancy data reassuring for this generally younger group. These data reinforce the importance of germline BRCA testing at the time of diagnosis, so we can identify all eligible patients who may benefit from treatment with olaparib as early as possible.” Breast cancer is the second most diagnosed cancer worldwide, with an estimated 2.3 million patients diagnosed in 2022. About 63% of all breast cancer patients are diagnosed at an early stage of disease and BRCA mutations are found in approximately 5-10% of patients. Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “ Two years ago, LYNPARZA became the first and only PARP inhibitor to demonstrate a survival benefit in germline BRCA - mutated, HER2-negative and high-risk early-stage breast cancer. To see this benefit continue after six years of follow-up is tremendous for patients and reinforces how LYNPARZA is continuing to transform the treatment of BRCA - mutated early-stage breast cancer.” Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, said: “ The durable long-term efficacy seen in the OlympiA study reinforces LYNPARZA as an important treatment option for those living with this truly challenging, very aggressive form of breast cancer.” At a median follow-up of 6.1 years (maximum 9.6 years) in eligible patients, who had completed local treatment and standard neoadjuvant or adjuvant chemotherapy, LYNPARZA reduced the risk of death by 28% (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.56-0.93) versus placebo. In addition, 87.5% of patients treated with LYNPARZA remained alive versus 83.2% of those on placebo. LYNPARZA also demonstrated sustained and clinically meaningful improvements in the primary and secondary endpoints of IDFS and DDFS. LYNPARZA reduced the risk of invasive breast cancer recurrence, second cancers or death by 35% (HR 0.65; 95% CI; 0.53-0.78) and reduced the risk of distant disease recurrence or death by 35% (HR 0.65; 95% CI; 0.53-0.81) versus placebo. The benefit with LYNPARZA was consistent across all key subgroups, including patients with high-risk, hormone-receptor-positive disease. Summary of results LYNPARZA (n=921) Placebo (n=915) IDFS (primary endpoint) HR (95% CI) 0.65 (0.53, 0.78) IDFS rates at 6 years 79.6% 70.3% DDFS (secondary endpoint) HR (95% CI) 0.65 (0.53, 0.81) DDFS rates at 6 years 83.5% 75.7% OS (secondary endpoint) HR (95% CI) 0.72 (0.56, 0.93) OS rates at 6 years 87.5% 83.2% The safety and tolerability profile of LYNPARZA in this trial was in line with that observed in prior clinical trials and no new safety signals were identified with longer follow-up. No evidence of an increased risk of myelodysplastic syndrome or acute myeloid leukemia was observed compared to those on placebo. The OlympiA trial is coordinated by the Breast International Group (BIG) in partnership with NRG Oncology, the US National Cancer Institute (NCI), the Frontier Science & Technology Research Foundation (FSTRF), AstraZeneca and Merck. 5 LYNPARZA is approved in the United States (US), European Union (EU), Japan, and many other countries for the treatment of gBRCAm, HER2-negative high-risk early breast cancer based on the results of the OlympiA Phase 3 trial. LYNPARZA is also approved in the US, EU, Japan, and many other countries for the treatment of patients with gBRCAm, HER2-negative, metastatic breast cancer. In the EU, this indication also includes patients with locally advanced breast cancer. About OlympiA OlympiA is a phase III, double-blind, parallel group, placebo-controlled, multicenter trial evaluating the efficacy and safety of LYNPARZA tablets versus placebo as a 12-month adjuvant treatment for adult patients with gBRCAm HER2-negative early breast cancer, who have completed neoadjuvant or adjuvant chemotherapy. 5 The primary endpoint of the trial is invasive disease-free survival defined as time from randomization to date of first loco-regional or distant recurrence or new cancer or death from any cause. Key secondary endpoints include distant disease-free survival and overall survival, which is defined as time from randomization until documented evidence of first distant recurrence of breast cancer or death without distant recurrence. 5 IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS There are no contraindications for LYNPARZA. WARNINGS AND PRECAUTIONS Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately 1.2% of patients with various BRCA m, gBRCAm, HRR gene-mutated or HRD-positive cancers who received LYNPARZA as a single agent or as part of a combination regimen, consistent with the approved indications, and the majority of events had a fatal outcome. The median duration of therapy in patients who developed MDS/AML was approximately 2 years (range: <6 months to >4 years). All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy. In SOLO-1, patients with newly diagnosed advanced BRCAm ovarian cancer, the incidence of MDS/AML was 1.9% (5/260) in patients who received LYNPARZA and 0.8% (1/130) in patients who received placebo based on an updated analysis. In PAOLA-1, of patients with newly diagnosed advanced ovarian cancer with HRD-positive status, the incidence of MDS/AML was 1.6% (4/255) in patients who received LYNPARZA and 2.3% (3/131) in the control arm. In SOLO-2, patients with BRCAm platinum-sensitive relapsed ovarian cancer, the incidence of MDS/AML was 8% (15/195) in patients who received LYNPARZA and 4% (4/99) in patients who received placebo. The duration of LYNPARZA treatment prior to the diagnosis of MDS/AML ranged from 0.6 years to 4.5 years. 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. Venous Thromboembolism (VTE): Including severe or fatal pulmonary embolism (PE) occurred in patients treated with LYNPARZA. In the combined data of two randomized, placebo-controlled clinical studies (PROfound and PROpel) in patients with metastatic castration-resistant prostate cancer (N=1180), VTE occurred in 8% of patients who received LYNPARZA, including pulmonary embolism in 6%. In the control arms, VTE occurred in 2.5%, including pulmonary embolism in 1.5%. 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. Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. Verify pregnancy status in 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. ADVERSE REACTIONS—First-Line Maintenance BRCA m 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 and at a ≥5% frequency compared to 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 g BRCA m 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%). Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the maintenance setting for SOLO-2 were: increase in mean corpuscular volume (89%), decrease in hemoglobin (83%), decrease in leukocytes (69%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), increase in serum creatinine (44%), and decrease in platelets (42%). ADVERSE REACTIONS—Adjuvant Treatment of g BRCA m, 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—g BRCA m, 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 g BRCA m 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%). ADVERSE REACTIONS—Metastatic Castration-Resistant Prostate Cancer in Combination with Abiraterone and Prednisone or Prednisolone Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA/abiraterone with a difference of ≥5% compared to placebo for PROpel were: anemia (48%), fatigue (including asthenia) (38%), nausea (30%), diarrhea (19%), decreased appetite (16%), lymphopenia (14%), dizziness (14%), and abdominal pain (13%). Most common laboratory abnormalities (Grades 1-4) in ≥20% of patients who received LYNPARZA/abiraterone for PROpel were: decrease in hemoglobin (97%), decrease in lymphocytes (70%), decrease in platelets (23%), and decrease in absolute neutrophil count (23%). 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 BRCA m Advanced Ovarian Cancer For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA -mutated (g BRCA m or s BRCA m) 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 BRCA -mutated Recurrent Ovarian Cancer For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (g BRCA m or s BRCA m) recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA. Adjuvant Treatment of g BRCA m, HER2-Negative, High-Risk Early Breast Cancer For the adjuvant treatment of adult patients with deleterious or suspected deleterious g BRCA m, 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. g BRCA m, HER2-Negative Metastatic Breast Cancer For the treatment of adult patients with deleterious or suspected deleterious g BRCA m , 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 g BRCA m Metastatic Pancreatic Cancer For the maintenance treatment of adult patients with deleterious or suspected deleterious g BRCA m 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. BRCA m Metastatic Castration-Resistant Prostate Cancer in Combination with Abiraterone and Prednisone or Prednisolone In combination with abiraterone and prednisone or prednisolone (abi/pred) for the treatment of adult patients with deleterious or suspected deleterious BRCA -mutated ( BRCA m) metastatic castration-resistant prostate cancer (mCRPC). Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA. Please see complete Prescribing Information , including Medication Guide . About LYNPARZA ® (olaparib) LYNPARZA is a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. 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. LYNPARZA is being tested in a range of tumor types with defects and dependencies in the DDR. LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has a broad and advanced clinical trial development program, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types. About BRCA Mutations BRCA 1 and BRCA 2 (breast cancer susceptibility genes 1/2) are human genes that produce proteins responsible for repairing damaged DNA and play an important role maintaining the genetic stability of cells. When either of these genes is mutated or altered such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop genetic alterations that can lead to cancer. About breast cancer Early breast cancer is defined as disease confined to the breast with or without regional lymph node involvement, and the absence of distant metastatic disease. In the US, the 5-year survival rate is 99.6% for localized breast cancer (only found in the breast area) and 86.7% for regional breast cancer (cancer that has spread outside the breast to nearby structures or lymph nodes). Despite advancements in the treatment of early breast cancer, up to 30% of patients with high-risk clinical and/or pathologic features recur within the first few years and patients with g BRCA mutations are more likely to be diagnosed at a younger age than those without these mutations. Breast cancer is one of the most biologically diverse tumor types with various factors fuelling its development and progression. The discovery of biomarkers in the development of breast cancer has greatly impacted scientific understanding of the disease. About the AstraZeneca and Merck strategic oncology collaboration In July 2017, AstraZeneca and Merck, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize certain oncology products including LYNPARZA, the world’s first PARP inhibitor, for multiple cancer types. Working together, the companies will develop these products in combination with other potential new medicines and as monotherapies. Independently, the companies will develop these oncology products in combination with their respective PD-L1 and PD-1 medicines. Merck’s focus on cancer Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials . About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter , Facebook , Instagram , YouTube and LinkedIn . Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2023 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site ( www.sec.gov ). Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .