RAHWAY, NJ, USA I March 21, 2024 I Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the Phase 3 KEYLYNK-006 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with maintenance LYNPARZA, a PARP inhibitor, did not meet its dual primary endpoints of overall survival (OS) and progression-free survival (PFS) for the first-line treatment of certain patients with metastatic nonsquamous non-small cell lung cancer (NSCLC).
In the KEYLYNK-006 trial, KEYTRUDA in combination with chemotherapy followed by KEYTRUDA plus maintenance LYNPARZA did not meet the study’s pre-specified statistical criteria for OS or PFS compared to KEYTRUDA in combination with chemotherapy (pemetrexed plus carboplatin or cisplatin) followed by KEYTRUDA plus maintenance chemotherapy (pemetrexed). The safety profiles of KEYTRUDA and LYNPARZA in this trial were consistent with those observed in previously reported studies for the individual therapies. A full evaluation of the data from this study is ongoing. Merck will work with investigators to share the results with the scientific community.
“As lung cancer continues to be the leading cause of cancer death worldwide, we are committed to exploring KEYTRUDA-based combinations and novel candidates that may further help improve patient outcomes,” said Dr. Gregory Lubiniecki, vice president, global clinical development, Merck Research Laboratories. “These results are an important reminder of how challenging it may be to treat these patients with metastatic nonsquamous non-small cell lung cancer. We sincerely thank the patients and investigators for their important contributions to this study.”
About KEYLYNK-006
KEYLYNK-006 is a randomized, open-label, two-phase Phase 3 trial (ClinicalTrials.gov, NCT03976323) evaluating KEYTRUDA in combination with chemotherapy (pemetrexed plus carboplatin or cisplatin) followed by either KEYTRUDA plus maintenance LYNPARZA or KEYTRUDA plus maintenance chemotherapy (pemetrexed) for the first-line treatment of patients with metastatic nonsquamous NSCLC with no epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) or proto-oncogene tyrosine-protein kinase (ROS1) genomic tumor aberrations. The dual primary endpoints are PFS per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR) and OS. The secondary endpoints include safety and health-related quality of life assessments. The trial enrolled an estimated 1,005 patients in the Induction Phase and randomized 672 patients with a complete or partial response or with stable disease. In the Induction Phase, patients received KEYTRUDA (200 mg intravenously [IV]) in combination with pemetrexed plus investigator’s choice of platinum chemotherapy, consisting of either carboplatin Area Under the Curve (AUC) (5 mg/mL/min IV) or cisplatin (75 mg/m2 IV) every three weeks (Q3W) for four cycles. In the Maintenance Phase, patients with a complete or partial response or with stable disease after completing four cycles of induction therapy were randomized to receive either KEYTRUDA (200 mg IV Q3W for up to 31 cycles) plus maintenance LYNPARZA (300 mg orally twice daily) or KEYTRUDA (200 mg IV Q3W for up to 31 cycles) plus maintenance pemetrexed (500 mg/m2 IV Q3W) until progressive disease, physician decision or intolerable toxicity.
About lung cancer
Lung cancer is the leading cause of cancer death worldwide. In 2022 alone, there were approximately 2.4 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 80% of all cases. In 2024, the overall five-year survival rate for patients diagnosed with lung cancer is 25% in the United States. Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced.
About Merck’s research in lung cancer
Merck is advancing research aimed at transforming the way lung cancer is treated, with a goal of improving outcomes for patients affected by this deadly disease. Through nearly 200 clinical trials evaluating more than 36,000 patients around the world, Merck is at the forefront of lung cancer research. In NSCLC, KEYTRUDA has six approved U.S. indications (see indications below) and is approved for advanced disease in more than 95 countries. Among Merck’s research efforts are trials focused on evaluating KEYTRUDA in earlier stages of lung cancer as well as identifying new combinations and coformulations with KEYTRUDA.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD- L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
- stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Carcinoma
KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC).
KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):
- who are not eligible for any platinum-containing chemotherapy, or
- who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumor express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
- in combination with platinum- and fluoropyrimidine-based chemotherapy, or
- as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Cervical Cancer
KEYTRUDA, in combination with chemoradiotherapy (CRT), is indicated for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer.
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1–containing regimen.
Biliary Tract Cancer
KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
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.
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 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.
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 BRCA-mutated Recurrent Ovarian Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) 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 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.
BRCAm 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 (BRCAm) 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.
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 X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
SOURCE: Merck
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RAHWAY, NJ, USA I March 21, 2024 I Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the Phase 3 KEYLYNK-006 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with maintenance LYNPARZA, a PARP inhibitor, did not meet its dual primary endpoints of overall survival (OS) and progression-free survival (PFS) for the first-line treatment of certain patients with metastatic nonsquamous non-small cell lung cancer (NSCLC).
In the KEYLYNK-006 trial, KEYTRUDA in combination with chemotherapy followed by KEYTRUDA plus maintenance LYNPARZA did not meet the study’s pre-specified statistical criteria for OS or PFS compared to KEYTRUDA in combination with chemotherapy (pemetrexed plus carboplatin or cisplatin) followed by KEYTRUDA plus maintenance chemotherapy (pemetrexed). The safety profiles of KEYTRUDA and LYNPARZA in this trial were consistent with those observed in previously reported studies for the individual therapies. A full evaluation of the data from this study is ongoing. Merck will work with investigators to share the results with the scientific community.
“As lung cancer continues to be the leading cause of cancer death worldwide, we are committed to exploring KEYTRUDA-based combinations and novel candidates that may further help improve patient outcomes,” said Dr. Gregory Lubiniecki, vice president, global clinical development, Merck Research Laboratories. “These results are an important reminder of how challenging it may be to treat these patients with metastatic nonsquamous non-small cell lung cancer. We sincerely thank the patients and investigators for their important contributions to this study.”
About KEYLYNK-006
KEYLYNK-006 is a randomized, open-label, two-phase Phase 3 trial (ClinicalTrials.gov, NCT03976323) evaluating KEYTRUDA in combination with chemotherapy (pemetrexed plus carboplatin or cisplatin) followed by either KEYTRUDA plus maintenance LYNPARZA or KEYTRUDA plus maintenance chemotherapy (pemetrexed) for the first-line treatment of patients with metastatic nonsquamous NSCLC with no epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) or proto-oncogene tyrosine-protein kinase (ROS1) genomic tumor aberrations. The dual primary endpoints are PFS per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR) and OS. The secondary endpoints include safety and health-related quality of life assessments. The trial enrolled an estimated 1,005 patients in the Induction Phase and randomized 672 patients with a complete or partial response or with stable disease. In the Induction Phase, patients received KEYTRUDA (200 mg intravenously [IV]) in combination with pemetrexed plus investigator’s choice of platinum chemotherapy, consisting of either carboplatin Area Under the Curve (AUC) (5 mg/mL/min IV) or cisplatin (75 mg/m2 IV) every three weeks (Q3W) for four cycles. In the Maintenance Phase, patients with a complete or partial response or with stable disease after completing four cycles of induction therapy were randomized to receive either KEYTRUDA (200 mg IV Q3W for up to 31 cycles) plus maintenance LYNPARZA (300 mg orally twice daily) or KEYTRUDA (200 mg IV Q3W for up to 31 cycles) plus maintenance pemetrexed (500 mg/m2 IV Q3W) until progressive disease, physician decision or intolerable toxicity.
About lung cancer
Lung cancer is the leading cause of cancer death worldwide. In 2022 alone, there were approximately 2.4 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 80% of all cases. In 2024, the overall five-year survival rate for patients diagnosed with lung cancer is 25% in the United States. Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced.
About Merck’s research in lung cancer
Merck is advancing research aimed at transforming the way lung cancer is treated, with a goal of improving outcomes for patients affected by this deadly disease. Through nearly 200 clinical trials evaluating more than 36,000 patients around the world, Merck is at the forefront of lung cancer research. In NSCLC, KEYTRUDA has six approved U.S. indications (see indications below) and is approved for advanced disease in more than 95 countries. Among Merck’s research efforts are trials focused on evaluating KEYTRUDA in earlier stages of lung cancer as well as identifying new combinations and coformulations with KEYTRUDA.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD- L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
- stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Carcinoma
KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC).
KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):
- who are not eligible for any platinum-containing chemotherapy, or
- who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumor express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
- in combination with platinum- and fluoropyrimidine-based chemotherapy, or
- as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Cervical Cancer
KEYTRUDA, in combination with chemoradiotherapy (CRT), is indicated for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer.
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1–containing regimen.
Biliary Tract Cancer
KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
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.
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 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.
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 BRCA-mutated Recurrent Ovarian Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) 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 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.
BRCAm 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 (BRCAm) 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.
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 X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
SOURCE: Merck
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