Merck’s KEYTRUDA® (pembrolizumab) Demonstrated Long-Term Survival Benefit Based on Four and Five Years of Follow-Up from Two Pivotal Studies in Advanced Melanoma

New Analysis of Four-Year Data for KEYTRUDA from Phase 3 KEYNOTE-006 Study Showed 86 Percent of Patients Were Progression-Free 20 Months After Completing Two Years of KEYTRUDA

Five-Year Data for KEYTRUDA from Phase 1b KEYNOTE-001 Study Showed Overall Survival Greater Than 40 Percent in Treatment-Naïve Metastatic Melanoma Patients, the Longest Follow-up for KEYTRUDA to Date

Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced long-term efficacy data from the Phase 3 KEYNOTE-006 study and the melanoma cohort of the Phase 1b KEYNOTE-001 study investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in patients with advanced melanoma. A new analysis from KEYNOTE-006 demonstrated durable efficacy benefits among patients who completed two years of KEYTRUDA treatment, combined with updated overall survival (OS) results across both studies, confirming anti-tumor activity in advanced melanoma patients. At a median follow-up of 20.3 months after completion of KEYTRUDA in KEYNOTE-006, 86 percent of patients remained progression-free, the co-primary endpoint for the study. For the primary endpoint of OS in KEYNOTE-006, the four-year OS rate was 41.7 percent in the pooled KEYTRUDA arms vs. 34.1 percent in the ipilimumab arm; in treatment-naïve patients, OS rates were 44.3 percent in the pooled KEYTRUDA arms and 36.4 percent in the ipilimumab arm. In KEYNOTE-001, the five-year OS rate, a secondary endpoint for the study, was 34 percent in all patients and 41 percent in treatment-naïve patients. The safety profile of KEYTRUDA in both studies was consistent with what has been seen in previous trials among patients with advanced melanoma. Results for KEYNOTE-006 (Abstract #9503) and KEYNOTE-001 (Abstract #9516) are being presented today at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting.

“Looking across the findings for both KEYNOTE-006 and KEYNOTE-001 we are seeing further validation that KEYTRUDA is significantly extending the survival of first-line metastatic melanoma patients, regardless of tumor BRAF-mutation status,” said Scot Ebbinghaus, M.D., vice president, clinical research, Merck Research Laboratories. “In KEYNOTE-006, we are also seeing durable efficacy benefits for patients who complete two years of KEYTRUDA treatment. We are pleased to share data that further reinforce KEYTRUDA monotherapy as a standard of care in advanced melanoma patients and deliver on our goal of improving and extending the lives of melanoma patients.”

“Pembrolizumab had already established superior survival outcomes versus ipilimumab in advanced melanoma patients, and this is further reinforced with four years of data in KEYNOTE-006,” said Professor Georgina V. Long, conjoint medical director of Melanoma Institute Australia (MIA), and chair of Melanoma Medical Oncology and Translational Research at MIA and Royal North Shore Hospital, The University of Sydney. “Importantly, we’re now seeing ongoing efficacy for patients who complete the protocol-specified two years of pembrolizumab treatment, as well as additional anti-tumor activity for the patients who progress after a first course of treatment and complete a second course of treatment.”

“Updated data for KEYNOTE-001 demonstrate significant survival benefits in advanced melanoma patients,” said Omid Hamid, M.D., chief of Translational Research and Immuno-Oncology and director of Melanoma Therapeutics, The Angeles Clinic and Research Institute, Los Angeles, California. “Five-year survival is a true milestone for oncology patients, particularly among those living with metastatic melanoma, so it is incredibly exciting to share these updated data.”

Merck’s long-term commitment to melanoma includes a broad clinical development program studying KEYTRUDA as monotherapy and in combination with other novel mechanisms. The program, which is comprised of more than 4,500 patients across 10 Merck-sponsored clinical studies, is evaluating KEYTRUDA across all settings and stages of the disease.

Additional Data and Safety Information from KEYNOTE-006 (Abstract #9503)

KEYNOTE-006 is a global, open-label, randomized, pivotal, Phase 3 study (ClinicalTrials.gov, NCT01866319) evaluating KEYTRUDA compared to ipilimumab in patients with unresectable stage III or IV melanoma who had either not been treated previously (first-line treatment setting) or who had received a prior targeted therapy for BRAF-mutation positive melanoma (in the KEYTRUDA arm, 34% received prior therapy with a BRAF/MEK inhibitor; in the ipilimumab arm, 35% received prior therapy). The study randomized 834 patients to receive KEYTRUDA 10 mg/kg every three weeks, KEYTRUDA 10 mg/kg every two weeks, or four cycles of ipilimumab 3 mg/kg every three weeks. Treatment continued until unacceptable toxicity or disease progression; patients without disease progression could be treated for up to 24 months. Upon disease progression, eligible patients could receive an additional one year of KEYTRUDA. The co-primary endpoints were progression-free survival (PFS) and OS; secondary endpoints were overall response rate (ORR), duration of response (DOR) and safety, with an exploratory analysis for health-related quality of life (QoL).

With a median follow-up of 45.9 months (range, 0.3-50.0), the four-year OS rate was 41.7 percent in the pooled KEYTRUDA arms (n=556) and 34.1 percent in the ipilimumab arm (n=278); investigator-reported ORR was 42 percent and 17 percent, respectively. Median DOR was not reached for KEYTRUDA (range, 1.0+ to 46.1+ months) or ipilimumab (range, 1.1+ to 45.6+ months); 62 percent of patients in the KEYTRUDA arms and 59 percent of patients in the ipilimumab arm had a response lasting ≥ 42 months.

In treatment-naïve patients, the four-year OS rates were 44.3 percent in the pooled KEYTRUDA arms (n=368) and 36.4 percent in the ipilimumab arm (n=181); ORR was 47 percent and 17 percent, respectively. Median DOR was not reached for KEYTRUDA (range, 1.6+ to 46.0+ months) or ipilimumab (range, 1.1+ to 42.2+ months); 65 percent of patients in the KEYTRUDA arms and 68 percent of patients in the ipilimumab arm had a response lasting ≥ 42 months.

Per study protocol, 18.5 percent of patients (n=103) completed two years of KEYTRUDA. With a median follow-up of 20.3 months (range, 0.03-24.8), 86 percent of patients (n=89) remained progression-free. Eight patients received second-course KEYTRUDA; three discontinued treatment. Among the eight patients, there was one complete response and three partial responses; three patients had stable disease, while the remaining patient had progressive disease.

The safety profile of KEYTRUDA was consistent with what has been seen in previously reported studies among patients with advanced melanoma. Five patients had an immune-mediated adverse event during second-course KEYTRUDA; there were no grade 3-4 immune-mediated adverse events or deaths.

Additional Data and Safety Information from KEYNOTE-001 (Abstract #9516)

KEYNOTE-001 is a Phase 1b multicenter, open-label, multi-cohort trial (ClinicalTrials.gov, NCT01295827) evaluating KEYTRUDA in various advanced cancers, including 655 patients with advanced melanoma. Patients in the melanoma cohorts received 2 mg/kg or 10 mg/kg of KEYTRUDA every three weeks or 10 mg/kg of KEYTRUDA every two weeks until unacceptable toxicity or disease progression. The primary endpoint was confirmed ORR. The secondary endpoints included PFS, OS and DOR.

After median follow-up of 55 months (range, 48-69), 35 patients remained on KEYTRUDA therapy. The investigator-reported ORR, the primary endpoint for KEYNOTE-001, was 41 percent in all patients (including 16% who achieved a complete response) and 52 percent in treatment-naïve patients (including 25% who achieved a complete response). The estimated five-year OS rate was 34 percent in all patients (n=655) and 41 percent in treatment naïve patients (n=151). Median OS was 23.8 months (95% CI, 20.2-30.4) in all patients and 38.6 months (95% CI, 27.2-NR) in treatment-naïve patients.

Median PFS was 8.3 months (95% CI, 5.8-11.1) and 16.9 months (95% CI, 9.3-35.5) in all patients and treatment-naïve patients, respectively.

Median DOR was not reached (range, 1.3+ to 66.3+ months) in all responders and in treatment-naïve patients (range, 1.3+ to 60.8+ months); 73 percent of all responses and 82 percent of treatment-naïve responses were ongoing at data cut-off. The longest response observed in all patients was ongoing at 66 months.

The safety profile of KEYTRUDA was consistent with what has been seen in previously reported studies among patients with advanced melanoma. Treatment-related adverse events (TRAEs) occurred in 86 percent (n=562) of patients including 17 percent with grade 3-4 and eight percent who discontinued. Twelve percent of patients experienced a serious TRAE including five percent who discontinued treatment. Immune-mediated adverse events and infusion reactions were reported in 23 percent of patients. Most cases of immune-related adverse events, including hypothyroidism and pneumonitis, were grade 1 or 2. Hypothyroidism was the most commonly reported immune-mediated adverse event, followed by pneumonitis, colitis and skin disorders.

About Melanoma

Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. The incidence of melanoma has been increasing over the past four decades – approximately 232,000 new cases were diagnosed worldwide in 2012. In the U.S., melanoma is one of the most common types of cancer diagnosed and is responsible for the vast majority of skin cancer deaths. In 2018, an estimated 91,270 people are expected to be diagnosed and an estimated 9,320 people are expected to die of the disease in the U.S. alone.

Merck Investor Webcast

Merck will hold an investor event in conjunction with the 2018 ASCO Annual Meeting today, Monday, June 4 at 5:45 p.m. CT. Those unable to attend in person will be able to listen to a live audio webcast of the presentation. Those interested in participating can register and join here.

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.

Merck has the industry’s largest immuno-oncology clinical research program, which currently involves more than 750 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.

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 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 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 children 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.

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 [Combined Positive Score (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. The recommended dose of KEYTRUDA is 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

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 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.com and connect with us on TwitterFacebookInstagram, YouTube and LinkedIn.

SOURCE: Merck

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