Study Results Confirm KEYTRUDA is the Only Anti-PD-1 Therapy to Show an Overall Survival Benefit as Monotherapy in First-Line NSCLC

KEYNOTE-042 to be Presented in Plenary Session at 2018 ASCO Annual Meeting

KENILWORTH, NJ, USA I June 03, 2018 I Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced results from KEYNOTE-042, a pivotal, Phase 3 study evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the first-line treatment of locally advanced or metastatic nonsquamous or squamous non-small cell lung cancer (NSCLC) without EGFR or ALK genomic tumor aberrations. In this study, KEYTRUDA monotherapy resulted in significantly longer overall survival (OS) than platinum-based chemotherapy (carboplatin plus paclitaxel or carboplatin plus pemetrexed) in patients with a PD-L1 tumor proportion score (TPS) of ≥1 percent. As part of a pre-specified analysis plan, OS was sequentially tested and was significantly improved in patients with a TPS of ≥50 percent (HR=0.69 [95% CI, 0.56-0.85]; p=0.0003), with a TPS of ≥20 percent (HR=0.77 [95% CI, 0.64-0.92]; p=0.0020), and then in the entire study population with a TPS of ≥1 percent (HR=0.81 [95% CI, 0.71-0.93]; p=0.0018). These results will be presented today in the plenary session and during the Sunday press program at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #LBA4).

“In the entire KEYNOTE-042 study population of patients expressing PD-L1 in at least 1 percent of tumor cells, first-line treatment with KEYTRUDA as monotherapy significantly improved overall survival in patients with either locally advanced or metastatic non-small cell lung cancer across histologies,” said Dr. Gilberto Lopes, study investigator and associate director for global oncology at the Sylvester Comprehensive Cancer Center at the University of Miami. “As a clinician treating patients with advanced lung cancer every day, it is encouraging to have additional data on KEYTRUDA’s benefits on overall survival, the primary goal of therapy for patients newly diagnosed with this deadly disease.”

“As monotherapy and in the combination setting, data continue to support the favorable effect of treatment with KEYTRUDA on overall survival,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “We look forward to submitting these data to global regulatory authorities, with the goal of making KEYTRUDA available to all of those patients who might potentially benefit from its use.”

Merck has an extensive clinical development program in lung cancer and is advancing multiple registration-enabling studies with KEYTRUDA in combination with other treatments and as monotherapy. The program, which is comprised of nearly 9,000 patients across 15 Merck-sponsored clinical studies, is evaluating KEYTRUDA across multiple settings and stages of the disease.

Additional Data from KEYNOTE-042 (Abstract #LBA4)

KEYNOTE-042 is an international, randomized, open-label Phase 3 study (ClinicalTrials.gov, NCT02220894) investigating KEYTRUDA monotherapy compared to standard of care platinum-based chemotherapy in patients with locally advanced or metastatic PD-L1 positive (TPS ≥1%) NSCLC. Patients had no EGFR or ALK genomic tumor aberrations and had not previously received systemic therapy for advanced disease. The primary endpoint is OS with TPS of ≥50 percent, ≥20 percent and ≥1 percent, which was assessed sequentially. Secondary endpoints are progression-free survival (PFS) and objective response rate (ORR), which were also sequentially tested.

For patients in the KEYTRUDA arm compared with chemotherapy, median OS was 20.0 vs. 12.2 months for patients with a TPS of ≥50 percent, 17.7 vs. 13.0 months for patients with a TPS of ≥20 percent, and 16.7 vs. 12.1 months for the overall study population of patients with a TPS of ≥1 percent. An exploratory subgroup analysis was conducted in patients with a TPS of 1-49 percent, which showed an OS HR of 0.92 (95% CI, 0.77-1.11). At the time of the current interim analysis, KEYTRUDA reduced disease progression or death (PFS) by 19 percent in the PD-L1 TPS ≥50 percent population, which was not statistically significant (HR=0.81 [95% CI, 0.67-0.99]; p=0.0170). Per the pre-specified sequential testing plan, PFS in the TPS ≥20% and ≥1% populations was not formally tested since superiority was not met for the preceding hypothesis (PFS in patients with TPS ≥50 percent). Based on the recommendation of the external Data Monitoring Committee (DMC), PFS will continue to be evaluated in a final analysis.

In KEYNOTE-042, ORR in the entire study population of TPS ≥1 percent was 27.3 percent for KEYTRUDA vs. 26.5 percent for chemotherapy, which was also not formally tested because of the pre-specified sequential testing plan. In addition, in patients with TPS ≥1 percent, the median duration of response (DOR) for patients in the KEYTRUDA arm was more than double that of the chemotherapy arm (20.2 months [range, 2.1+ to 31.2+ months] vs. 8.3 months [range, 1.8+ to 28.1+ months], respectively).

The safety of KEYTRUDA was consistent with what has been seen in previous trials among patients with metastatic NSCLC. Grade 3-5 treatment-related adverse events occurred in 17.8 percent of patients in the KEYTRUDA group and in 41.0 percent in the chemotherapy group. The most common immune-mediated adverse events of any grade and from any cause in patients receiving KEYTRUDA were hypothyroidism (12.1%), pneumonitis (8.3%), hyperthyroidism (6.1%), severe skin reactions (2.4%), thyroiditis (1.6%), hepatitis (1.4%), and colitis (1.1%). There were 13 treatment-related AEs that led to death in the KEYTRUDA group vs. 14 in the chemotherapy group, including one death from pneumonitis in the KEYTRUDA group.

Additional Information about KEYNOTE-042

In KEYNOTE-042, 1,274 patients were randomized 1:1 to receive either KEYTRUDA (200 mg fixed dose every three weeks) as monotherapy for up to 35 cycles, or investigator’s choice of platinum-based chemotherapy as follows:

  • carboplatin AUC 5 or 6 mg/mL/min plus paclitaxel 200 mg/m2 every three weeks for a maximum of six cycles for patients with squamous NSCLC; or
  • carboplatin AUC 5 or 6 mg/mL/min plus pemetrexed 500 mg/m2 every three weeks for a maximum of six cycles, followed by optional pemetrexed 500 mg/m2 for patients with nonsquamous NSCLC.

About Lung Cancer

Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. Each year, more people die of lung cancer than die of colon, breast and prostate cancers combined. The two main types of lung cancer are non-small cell and small cell. NSCLC is the most common type of lung cancer, accounting for about 85 percent of all cases. The five-year survival rate for patients diagnosed in the United States with any stage of lung cancer is estimated to be 18 percent.

Merck Investor Webcast

Merck will hold an investor event in conjunction with the 2018 ASCO Annual Meeting on 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