Merck’s KEYTRUDA® (pembrolizumab) Plus Chemotherapy Reduced Risk of Death by 27% Versus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Esophageal Cancer

KEYTRUDA Plus Chemotherapy Demonstrated Superior Overall Survival and Progression-Free Survival Versus Chemotherapy in These Patients Regardless of PD-L1 Expression Status and Tumor Histology

Results From Pivotal KEYNOTE-590 Trial Presented for the First Time at ESMO Virtual Congress 2020 During Presidential Symposium

KENILWORTH, NJ, USA I September 21, 2020 I Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced first-time data from the pivotal Phase 3 KEYNOTE-590 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with platinum-based chemotherapy (cisplatin plus 5-fluorouracil [5-FU]) for the first-line treatment of patients with locally advanced or metastatic esophageal and gastroesophageal junction (GEJ) cancer. In the study, KEYTRUDA in combination with chemotherapy significantly improved overall survival (OS), reducing the risk of death by 27% [HR=0.73 [95% CI, 0.62-0.86]; p<0.0001], versus chemotherapy in all randomized patients. KEYTRUDA in combination with chemotherapy also significantly improved progression-free survival (PFS), reducing the risk of disease progression or death by 35% or more than a third [HR=0.65 [95% CI, 0.55-0.76]; p<0.0001] in all randomized patients. With these results, KEYTRUDA is the first anti-PD-1 therapy in combination with chemotherapy to show superior OS, PFS and objective response rates (ORR) versus chemotherapy, the current standard of care, for these patients regardless of histology or PD-L1 expression status.

“Esophageal cancer is an aggressive disease that is associated with very poor survival, and there is an urgent need for advances for newly diagnosed, previously untreated patients,” said Dr. Ken Kato, chief, department of Head and Neck Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. “In KEYNOTE-590, with a 27% reduction in the risk of death, the results show KEYTRUDA has the potential to change the current treatment paradigm for the first-line treatment of patients with locally advanced and unresectable or metastatic esophageal or esophagogastric junction cancer. Results also showed a median overall survival of 12.4 months for KEYTRUDA versus 9.8 months for chemotherapy.”

“These findings for KEYTRUDA in combination with chemotherapy are particularly impressive considering improvement in overall survival was observed across all patient populations – including those patients with esophageal squamous cell carcinoma, adenocarcinoma and gastroesophageal junction tumors – and regardless of PD-L1 expression,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “Our goal is to extend the lives of people living with cancer, and these important findings add to a growing body of survival data for KEYTRUDA in a wide range of cancers.”

These late-breaking data were presented during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 on Monday, Sept. 21 (Abstract #LBA51). As announced, data spanning more than 15 types of cancer will be presented from Merck’s broad oncology portfolio and investigational pipeline at the congress. A compendium of presentations and posters of Merck-led studies is available here. Follow Merck on Twitter via @Merck and keep up to date with ESMO news and updates by using the hashtag #ESMO20.

Merck will be sharing these data with regulatory authorities worldwide. KEYTRUDA is currently approved in the U.S., China and Japan as monotherapy for the second-line treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10). Merck is continuing to study KEYTRUDA across multiple settings and stages of gastrointestinal cancer – including gastric, hepatobiliary, esophageal, pancreatic, colorectal and anal cancers – through its broad clinical program.

KEYNOTE-590 Trial Design and Additional Data (Abstract #LBA8)

KEYNOTE-590 is a Phase 3, randomized, double-blind trial (ClinicalTrials.gov, NCT03189719) that enrolled 749 patients and is evaluating KEYTRUDA in combination with chemotherapy, versus placebo plus chemotherapy (cisplatin plus 5-FU), for the first-line treatment of patients with locally advanced or metastatic esophageal carcinoma (including esophageal squamous cell carcinoma [ESCC] and adenocarcinoma of the esophagus) or Siewert type 1 GEJ. The primary endpoints are OS in patients with ESCC whose tumors expressed PD-L1 (CPS ≥10) and OS and PFS in patients with ESCC, in all randomized patients whose tumors expressed PD-L1 (CPS ≥10), and in all randomized patients. Secondary endpoints include ORR (per Response Evaluation Criteria in Solid Tumors [RECIST] v1.1 by investigator review) in all patients, duration of response (DOR) and safety. OS and PFS were tested using a hierarchical strategy, such that testing was first performed in patients with ESCC whose tumors expressed PD-L1 (CPS ≥10), with partial alpha passing from a successful test of the hypothesis, then in all patients with ESCC, then in all patients whose tumors expressed PD-L1 (CPS ≥10), and finally in all participants.

At the first interim analysis, after a median follow-up of 10.8 months, KEYTRUDA in combination with chemotherapy demonstrated superior OS versus chemotherapy in all randomized patients in the study (HR=0.73 [95% CI, 0.62-0.86]; p<0.0001), in patients with ESCC whose tumors expressed PD-L1 (CPS ≥10) (HR=0.57 [95% CI, 0.43-0.75]; p<0.0001), in patients with ESCC (HR=0.72 [95% CI, 0.60-0.88]; p=0.0006), and in patients whose tumors expressed PD-L1 (CPS ≥10) (HR=0.62 [95% CI, 0.49-0.78]; p<0.0001). In all randomized patients in the study, the median OS was 12.4 months (95% CI, 10.5-14.0) in the KEYTRUDA combination arm versus 9.8 months (95% CI, 8.8-10.8) in the chemotherapy arm. In patients with ESCC whose tumors expressed PD-L1 (CPS ≥10), the median OS was 13.9 months (95% CI, 11.1-17.7) in the KEYTRUDA combination arm versus 8.8 months (95% CI, 7.8-10.5) in the chemotherapy arm. In patients with ESCC, the median OS was 12.6 months (95% CI, 10.2-14.3) in the KEYTRUDA combination arm versus 9.8 months (95% CI, 8.6-11.1) in the chemotherapy arm. In patients whose tumors expressed PD-L1 (CPS ≥10), the median OS was 13.5 months (95% CI, 11.1-15.6) in the KEYTRUDA combination arm versus 9.4 months (95% CI, 8.0-10.7) in the chemotherapy arm.

KEYTRUDA in combination with chemotherapy demonstrated superior PFS versus chemotherapy in all randomized patients in the study (HR=0.65 [95% CI, 0.55-0.76]; p<0.0001), in patients with ESCC (HR=0.65 [95% CI, 0.54-0.78]; p<0.0001), and in patients whose tumors expressed PD-L1 (CPS ≥10) (HR=0.51 [95% CI, 0.41-0.65]; p<0.0001). In all randomized patients in the study, the median PFS was 6.3 months (95% CI, 6.2-6.9) in the KEYTRUDA combination arm versus 5.8 months (95% CI, 5.0-6.0) in the chemotherapy arm. In patients with ESCC, the median PFS was 6.3 months (95% CI, 6.2-6.9) in the KEYTRUDA combination arm versus 5.8 months (95% CI, 5.0-6.1) in the chemotherapy arm. In patients whose tumors expressed PD-L1 (CPS ≥10), the median PFS was 7.5 months (95% CI, 6.2-8.2) in the KEYTRUDA combination arm versus 5.5 months (95% CI, 4.3-6.0) in the chemotherapy arm.

KEYTRUDA in combination with chemotherapy demonstrated superior ORR versus chemotherapy in all randomized patients in the study. The ORR was 45.0% (95% CI, 39.9-50.2) in the KEYTRUDA combination arm versus 29.3% (95% CI, 24.7-34.1) in the chemotherapy arm (p<0.0001). Additionally, the median DOR was 8.3 months (range, 1.2+ to 31.0+) in the KEYTRUDA combination arm versus 6.0 months (range, 1.5+ to 25.0+) in the chemotherapy arm.

Treatment-related adverse events (TRAEs) led to discontinuation in 19.5% of patients in the KEYTRUDA combination arm and 11.6% of patients in the chemotherapy arm. Grade 3-5 TRAEs occurred in 71.9% of patients in the KEYTRUDA combination arm and 67.6% of patients in the chemotherapy arm. There were nine treatment-related deaths in the KEYTRUDA combination arm and five treatment-related deaths in the chemotherapy arm. Immune-mediated adverse events of any grade occurred in 25.7% of patients in the KEYTRUDA combination arm and 11.6% of patients in the chemotherapy arm.

About Esophageal Cancer

Esophageal cancer, a type of cancer that is particularly difficult to treat, begins in the inner layer (mucosa) of the esophagus and grows outward. The two main types of esophageal cancer are squamous cell carcinoma and adenocarcinoma. Esophageal cancer is the seventh most commonly diagnosed cancer and the sixth leading cause of death from cancer worldwide. Globally, it is estimated there were more than 572,000 new cases of esophageal cancer diagnosed and nearly 509,000 deaths resulting from the disease in 2018. In the U.S. alone, it is estimated there will be nearly 18,500 new cases of esophageal cancer diagnosed and more than 16,000 deaths resulting from the disease in 2020.

About KEYTRUDA® (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-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 1,200 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

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.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. 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 confirmatory trials.

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 head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. 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.

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. 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 confirmatory trials. 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 cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) ≥10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) 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 (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) 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, or
  • colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.

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 first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. 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 recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

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 patients with advanced renal cell carcinoma (RCC).

Tumor Mutational Burden-High

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] 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) that is not curable by surgery or radiation.

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

For more than 125 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

SOURCE: Merck

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