Merck Announces Findings from Phase 3 Study of KEYTRUDA® (pembrolizumab), Compared to Standard of Care, in Patients with Previously Treated Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

First Presentation of KEYNOTE-040 Results at ESMO 2017 Congress

KENILWORTH, NJ, USA I September 11, 2017 I Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced results of the phase 3 KEYNOTE-040 trial investigating KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, compared to standard treatment (methotrexate, docetaxel or cetuximab) in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. As previously disclosed, the study did not meet its pre-specified primary endpoint of overall survival (OS). The findings include updated survival data showing a 19 percent reduction in the risk of death over standard treatment in the intent-to-treat population (HR, 0.81 [95% CI, 0.66-0.99]; one sided p = 0.0204), with pre-specified p-value required for statistical significance of 0.0175, and a median OS of 8.4 months with KEYTRUDA (95% CI, 6.5-9.4) compared to 7.1 months with standard treatment (95% CI, 5.9-8.1). Complete results will be presented for the first time at the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid, Spain, in an oral presentation today from 3:00 – 3:12 p.m. CEST (Location: Granada Auditorium) (Abstract #LBA45_PR).

“These data, including progression-free survival and overall response rate, show the activity and efficacy of pembrolizumab in this disease, and are consistent with prior studies of pembrolizumab in recurrent head and neck squamous cell carcinoma,” said Ezra Cohen, M.D., associate director for translational science, Moores Cancer Center and co-director of the San Diego Center for Precision Immunotherapy, University of California, San Diego. “KEYNOTE-40 strengthens the rationale for further studies, and expansion into earlier lines of disease.”

With more than 20 trials, Merck currently has the largest immuno-oncology clinical development program in head and neck cancer and is advancing multiple registration-enabling studies investigating KEYTRUDA (pembrolizumab) as monotherapy and in combination with other cancer treatments – including KEYNOTE-048 and KEYNOTE-412.

“Although the primary efficacy analysis did not show a statistically significant improvement in overall survival, these data add to the evolving science for KEYTRUDA in head and neck cancer,” said Dr. Jon Cheng, associate vice president, Merck Research Laboratories.

Data in Second-Line Treatment Setting, KEYNOTE-040 (Abstract #LBA45_PR)

KEYNOTE-040 is a randomized, multi-center, phase 3 study investigating KEYTRUDA as a monotherapy (n=247) versus standard treatment (methotrexate, docetaxel or cetuximab) (n=248) in patients with recurrent or metastatic HNSCC (additional details on the trial design are provided below).

Data presented at ESMO are based on findings in the intent-to-treat population (n=495) and include analysis of efficacy endpoints based on PD-L1 expression using two measurements: PD-L1 CPS ≥1 (n=387) and PD-L1 TPS ≥50% (n=129). More than a third of patients in the intent-to-treat population went on to receive subsequent therapy, including 11 of 84 patients in the KEYTRUDA arm and 31 of 100 patients in the standard treatment arm who received subsequent treatment with an immune checkpoint inhibitor. Other subsequent treatments included chemotherapy, EGFR inhibitor, kinase inhibitor, other immunotherapy, and other treatments.

Data show that in the intent-to-treat population, the median OS was 8.4 months with KEYTRUDA (95% CI, 6.5-9.4) compared to 7.1 months with standard treatment (95% CI, 5.9-8.1) (HR, 0.81 [95% CI, 0.66-0.99]; one sided p = 0.0204); the 12-month OS rate was 37.3 percent with KEYTRUDA compared to 27.2 percent with standard treatment. Further analysis of the primary endpoint based on PD-L1 expression showed:

  • In patients with PD-L1 CPS ≥1, the median OS was 8.7 months with KEYTRUDA (95% CI, 6.9-11.4) and 7.1 months with standard treatment (95% CI, 5.7-8.6) (HR, 0.75 [95% CI, 0.59-0.95]; p = 0.0078); the 12-month OS rate was 40.1 percent with KEYTRUDA compared to 26.7 percent with standard treatment.
  • In patients with PD-L1 TPS ≥50%, the median OS was 11.6 months with KEYTRUDA (95% CI, 8.3-19.5) and 7.9 months with standard treatment (95% CI, 4.8-9.3) (HR, 0.54 [95% CI, 0.35-0.82]; p = 0.0017); the 12-month OS rate was 46.6 percent with KEYTRUDA compared to 25.8 percent with standard treatment.

The overall response rate (ORR) in the intent-to-treat population was 14.6 percent in the KEYTRUDA (pembrolizumab) arm compared to 10.1 percent in the standard treatment arm (p = 0.0610). In patients with PD-L1 CPS ≥1, the ORR was 17.3 percent with KEYTRUDA compared to 9.9 percent with standard treatment (p = 0.0171). In patients with PD-L1 TPS ≥50%, the ORR was 26.6 percent with KEYTRUDA compared to 9.2 percent with standard treatment (p = 0.0009).

The median progression-free survival (PFS) was 2.1 months in the intent-to-treat population with KEYTRUDA (95% CI, 2.1-2.3) and 2.3 months with standard treatment (95% CI, 2.1-2.8) (HR, 0.95 [95% CI, 0.79-1.16]; p = 0.3037). In patients with PD-L1 CPS ≥1, the median PFS was 2.2 months with KEYTRUDA (95% CI, 2.1-3.0) and 2.3 months with standard treatment (95% CI, 2.1-3.3) (HR, 0.89 [95% CI, 0.72-1.11]; p = 0.1526). In patients with PD-L1 TPS ≥50%, the median PFS was 3.5 months with KEYTRUDA (95% CI, 2.1-6.3) and 2.2 months with standard treatment (95% CI, 2.0-2.5) (HR, 0.58 [95% CI, 0.39-0.87]; p = 0.0034).

The safety profile of KEYTRUDA was consistent with that observed in previously reported studies. Treatment-related adverse events (TRAEs) of any grade occurred in 155 patients (63.0%) in the KEYTRUDA arm and 196 patients (83.8%) in the standard treatment arm. Across any arm, TRAEs with incidence of 10 percent or more included hypothyroidism, fatigue, diarrhea, rash, asthenia, anemia, nausea, mucosal inflammation, stomatitis, decreased neutrophil count and alopecia. Immune-mediated adverse events, any grade, occurring in the KEYTRUDA arm were hypothyroidism, pneumonitis, infusion reactions, severe skin reactions, hyperthyroidism, colitis, Guillain-Barre syndrome and hepatitis. Discontinuation due to TRAEs occurred in 15 patients (6.1%) in the KEYTRUDA arm and 12 patients (5.1%) in the standard treatment arm. Deaths due to treatment-related adverse events occurred in four patients (1.6%) in the KEYTRUDA arm and two patients (0.9%) in the standard treatment arm.

About KEYNOTE-040

KEYNOTE-040 is a randomized, multi-center, pivotal phase 3 study investigating KEYTRUDA as a monotherapy versus standard treatment (methotrexate, docetaxel or cetuximab) for the treatment of recurrent or metastatic HNSCC. The primary endpoint is OS; secondary endpoints include PFS and ORR. The study, which opened in November 2014, enrolled 495 patients to receive KEYTRUDA (200 mg fixed dose every three weeks) or investigator-choice chemotherapy (methotrexate [40 mg/m2 on Days 1, 8, and 15 of each 3-week cycle], docetaxel [75 mg/m2 on Day 1 of each 3-week cycle], or cetuximab [400 mg/m2 loading dose on Day 1 and 250 mg/m2 IV on Days 8 and 15 of Cycle 1], followed by cetuximab [250 mg/m2 on Days 1, 8, and 15 of each subsequent 3-week cycle]). Patients enrolled in the study had been previously treated with one to two platinum-containing systemic regimens.

About KEYTRUDA® (pembrolizumab) Injection 100mg

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.

Studies of KEYTRUDA – from the largest immuno-oncology program in the industry with more than 550 trials – include a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand factors that predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including the exploration of several different biomarkers across a broad range of tumors.

KEYTRUDA (pembrolizumab) Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, as a single agent, is also 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, in combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous NSCLC. This indication is approved under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

In metastatic NSCLC, KEYTRUDA (pembrolizumab) is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA should be administered prior to chemotherapy when given on the same day. See also the Prescribing Information for pemetrexed and carboplatin.

Head and Neck Cancer

KEYTRUDA 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. 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. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

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 three 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. In adults with cHL, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with cHL, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. 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 the confirmatory trials.

KEYTRUDA (pembrolizumab) is also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

In locally advanced or metastatic urothelial carcinoma, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Microsatellite Instability-High (MSI-H) 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.

In adult patients with MSI-H cancer, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with MSI-H cancer, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic 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 a century, Merck, a leading global biopharmaceutical company 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. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world - including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.comand connect with us on TwitterFacebookInstagram, YouTube and LinkedIn.

SOURCE: Merck

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