Merck To Present New Data From Its Broad Oncology Portfolio and Pipeline at ESMO 2021, Including in Earlier Stages of Cancer
Pivotal Phase 3 Data for KEYTRUDA® (pembrolizumab) in Stage II Melanoma (KEYNOTE-716) and Recurrent, Persistent or Metastatic Cervical Cancer (KEYNOTE-826) Selected for ESMO Presidential Symposium Sessions and Official Press Program
New Data for KEYTRUDA Demonstrate Significant Progress in Breast and Gynecological Cancer Clinical Programs
KENILWORTH, N.J.–(BUSINESS WIRE)–$MRK #MERCK–Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that data spanning 20 types of cancer from its leading oncology research program will be presented at the European Society for Medical Oncology (ESMO) Congress 2021 from Sept. 16–21. Key data include new Phase 3 results for the company’s oncology medicines, specifically: KEYTRUDA, Merck’s anti-PD-1 therapy in melanoma (KEYNOTE-716) and recurrent, persistent or metastatic cervical cancer (KEYNOTE-826), which were selected for inclusion in the ESMO Presidential Symposium sessions and the ESMO Press Program, and in metastatic triple-negative breast cancer (TNBC) (KEYNOTE-355); as well as LYNPARZA® (olaparib, in collaboration with AstraZeneca) in ovarian cancer; and LENVIMA® (lenvatinib, in collaboration with Eisai) in endometrial carcinoma and renal cell carcinoma. Additionally, new data for WELIREG™ (belzutifan) will also be presented.
“At this year’s ESMO, we’re pleased to share new and updated findings across our portfolio, including in stage II melanoma and in certain breast and cervical cancers, two common and challenging cancers faced by women,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “Merck has made significant progress in demonstrating the impact our medicines can have on people living with certain cancers, especially with those with hard-to-treat, metastatic disease. We continue to build on this knowledge as we advance important scientific research evaluating our medicines in earlier stages of disease, and in combination with other treatments, to help improve patient outcomes.”
Key Data from Merck’s Portfolio and Pipeline to be Presented at ESMO
- First presentation of data from the Phase 3 KEYNOTE-716 trial evaluating KEYTRUDA as adjuvant treatment for patients with surgically resected high-risk stage II melanoma (Abstract #LBA3), which met its primary endpoint of recurrence-free survival (RFS) and will be featured in an ESMO Presidential Symposium and as part of the ESMO Press Program.
- First-time results from the Phase 3 KEYNOTE-826 trial evaluating KEYTRUDA in combination with chemotherapy as first-line treatment with or without bevacizumab for patients with persistent, recurrent or metastatic cervical cancer (Abstract #LBA2), which will be featured in an ESMO Presidential Symposium and in the ESMO Press Program. Earlier this year, Merck reported KEYNOTE-826 met its primary endpoints of overall survival (OS) and progression-free survival (PFS) for the first-line treatment of these patients.
- Overall survival results from the Phase 3 KEYNOTE-355 trial evaluating KEYTRUDA in combination with chemotherapy as first-line treatment for patients with locally recurrent inoperable or metastatic TNBC (Abstract #LBA16). Earlier this year, Merck announced KEYTRUDA in combination with chemotherapy (nab-paclitaxel, paclitaxel or gemcitabine/carboplatin) demonstrated a statistically significant improvement in OS compared to chemotherapy alone in patients with metastatic TNBC whose tumors expressed PD-L1 (Combined Positive Score [CPS] ≥10).
- Encore presentation of the Phase 3 KEYNOTE-522 trial evaluating KEYTRUDA in combination with chemotherapy as neoadjuvant treatment and then continued as a single agent as adjuvant treatment for patients with high-risk early-stage TNBC (Abstract #VP7_2021) that met its dual primary endpoint of event-free survival (EFS) for the treatment of patients with high-risk early-stage TNBC.
Merck Investor Event
Members of the management team will host a virtual investor event during which they will highlight select datasets presented during the ESMO Congress 2021 on Sept. 20 at 4:30 p.m. ET. Webcast and dial-in details will be posted to the Investor Relations website closer to the event: https://www.merck.com/investor-relations/events-and-presentations/.
Details on Abstracts Listed Above and Additional Key Abstracts for Merck
Breast Cancer
- Abstract #LBA16, Proffered Paper: Final Results of KEYNOTE-355: A Randomized, Double-Blind, Phase 3 Study of Pembrolizumab + Chemotherapy vs Placebo + Chemotherapy for Previously Untreated Locally Recurrent Inoperable or Metastatic Triple-Negative Breast Cancer (TNBC). J. Cortes.
- Abstract # VP7_2021, Virtual Plenary Debate: KEYNOTE-522: Phase 3 Study of Pembrolizumab + Chemotherapy vs Placebo + Chemotherapy as Neoadjuvant Treatment, Followed by Pembrolizumab vs Placebo as Adjuvant Treatment for Early Triple-Negative Breast Cancer (TNBC). P. Schmid.
Gastrointestinal Cancers
- Abstract #432P, E-Poster: Pembrolizumab (Pembro) for Previously Treated, Microsatellite Instability-High (MSI-H)/Mismatch Repair-Deficient (dMMR) Metastatic Colorectal Cancer (mCRC): Final Analysis of KEYNOTE-164. D. Le.
- Abstract #1468P, E-Poster: POLO: Subsequent Therapy After Maintenance Olaparib in Patients With a Germline BRCA Mutation and Metastatic Pancreatic Cancer. T. Golan.
Genitourinary Cancer
- Abstract #61MO, Mini Oral: Biomarker Analysis of Men With Enzalutamide (Enza)-Resistant Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated With Pembrolizumab (Pembro) + Enza in KEYNOTE-199. J. Graff.
- Abstract #611P, E-Poster: Pembrolizumab (Pembro) Monotherapy for Docetaxel-Pretreated Metastatic Castration-Resistant Prostate Cancer (mCRPC): Updated Analyses With 4 Years of Follow-up From Cohorts 1-3 of the KEYNOTE-199 Study. S. Antonarakis.
- Abstract #612P, E-Poster: Pembrolizumab (Pembro) Plus Olaparib in Patients With Docetaxel-Pretreated Metastatic Castration-Resistant Prostate Cancer (mCRPC): Update of KEYNOTE-365 Cohort A With a Minimum of 11 Months of Follow-up for All Patients. E. Yu.
- Abstract #662P, E-Poster: Pembrolizumab (Pembro) Monotherapy as First-Line Therapy in Advanced Non-Clear Cell Renal Cell Carcinoma (nccRCC): Results With a Minimum of 34 Months of Follow-up From KEYNOTE-427 Cohort B. J. Lee.
- Abstract #653O, Mini Oral: Pembrolizumab (Pembro) vs Placebo as Adjuvant Therapy for Patients (Pts) With Renal Cell Carcinoma (RCC): Patient-Reported Outcomes (PRO) In KEYNOTE-564. T. Choueiri.
- Abstract #660P, E-Poster: Phase III CLEAR in Advanced Renal Cell Carcinoma (aRCC): Outcomes in Several Subgroups and Toxicity Update. T.Choueiri.
- Abstract #656MO, Mini Oral: Phase 2 Study of Belzutifan (MK-6482), an Oral Hypoxia-Inducible Factor 2α (HIF-2α) Inhibitor, Plus Cabozantinib for Treatment of Advanced Clear Cell Renal Cell Carcinoma (ccRCC). D. McDermott.
Gynecologic Cancers
- Abstract #LBA2, Presidential Symposium: KEYNOTE-826: A Randomized, Double-Blind, Phase 3 Study of Pembrolizumab + Chemotherapy vs Placebo + Chemotherapy for First-Line Treatment of Persistent, Recurrent, or Metastatic Cervical Cancer. N. Colombo.
- Abstract #LBA33, Proffered Paper: Maintenance Olaparib as Retreatment for Patients (Pts) With Platinum-Sensitive Relapsed (PSR) Ovarian Cancer (OC) Previously Treated With a PARP Inhibitor: Randomized Phase IIIb OReO Trial. E. Pujade-Lauraine.
- Abstract #795MO, Mini Oral: Pembrolizumab in Patients With Microsatellite Instability-High (MSI-H) Advanced Endometrial Cancer: Updated Results From the KEYNOTE-158 Study. D. O’Malley.
- Abstract #726MO, Mini Oral: Outcomes by Histology and Prior Therapy With Lenvatinib Plus Pembrolizumab vs Treatment of Physician’s Choice in Patients With Advanced Endometrial Cancer (Study 309/KEYNOTE-775). N. Colombo.
Melanoma
- Abstract #LBA3, Presidential Symposium: Pembrolizumab Versus Placebo After Complete Resection of High-Risk Stage II Melanoma: Efficacy and Safety Results From the KEYNOTE-716 Double-Blind Phase III Trial. J. Luke.
- Abstract #1073P, E-Poster: Quality of Life (QOL) Endpoints of the Phase III Intergroup S1404 Adjuvant Melanoma Trial. S. Patel.
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 1,500 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.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.
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.
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 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 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 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 MSI-H central nervous system cancers have not been established.
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).
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. 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.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or 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 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. 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.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. 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.
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). 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.
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, in combination with LENVIMA, is indicated for the first-line treatment of adult patients with advanced RCC.
Endometrial Carcinoma
KEYTRUDA, in combination with LENVIMA, is indicated for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy in any settings 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 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.
Selected Important Safety Information for KEYTRUDA
Severe and Fatal Immune-Mediated Adverse Reactions
KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the PD-1 or the PD-L1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.
Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.
Immune-Mediated Pneumonitis
KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.
Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.
Immune-Mediated Colitis
KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.
Hepatotoxicity and Immune-Mediated Hepatitis
KEYTRUDA as a Single Agent
KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.
KEYTRUDA with Axitinib
KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (20%) and increased aspartate aminotransferase (13%) were seen at a higher frequency compared to KEYTRUDA alone.
Contacts
Media Contacts:
Melissa Moody
(215) 407-3536
Kristen Drake
(908) 740-1679
Investor Contacts:
Peter Dannenbaum
(908) 740-1037
Raychel Kruper
(908) 740-2107
