KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced the presentation of five-year efficacy and safety data for KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy in patients with advanced non-small cell lung cancer (NSCLC) from the first KEYNOTE trial (Phase 1b KEYNOTE-001). In this study, KEYTRUDA demonstrated a five-year overall survival (OS) rate of 23.2% in treatment-naïve patients (n=101) and 15.5% in previously treated patients (n=449). Of note, the five-year OS rate among patients whose tumors expressed PD-L1 (tumor proportion score [TPS] ≥50%) was 29.6% in treatment-naïve patients (n=27) and 25.0% in previously treated patients (n=138). These findings, which represent the longest follow-up for KEYTRUDA in lung cancer, will be highlighted at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #LBA9015) during the official press program and presented during a poster discussion on Sunday, June 2.
“Lung cancer is the leading cause of cancer death, and historically, the five-year survival rate has been around 5% for patients in the U.S. with advanced non-small cell lung cancer,” said Edward B. Garon, MD, MS, associate professor of medicine, Jonsson Comprehensive Cancer Center, University of California, Los Angeles. “As a treating physician, it is encouraging to see the results of KEYNOTE-001, in which pembrolizumab showed a five-year overall survival rate of 23.2% in treatment-naïve patients and 15.5% in previously treated patients.”
After 60.6 months (range, 51.8 to 77.9) of median follow-up, results from KEYNOTE-001 demonstrated the effect of KEYTRUDA monotherapy across primary and secondary endpoints, including OS, objective response rate (ORR) and duration of response (DOR).
Median OS, mo
|TPS ≥50%||17/27||35.4 (20.3-63.5)||29.6|
|TPS 1%-49%||43/52||19.5 (10.7-26.3)||15.7|
|Previously treated||375/449†||10.5 (8.6-13.2)||15.5|
|TPS ≥50%||104/138||15.4 (10.6-18.8)||25.0|
|TPS 1%-49%||146/168||8.5 (6.0-12.6)||12.6|
|TPS <1%||83/90||8.6 (5.5-10.6)||3.5|
*PD-L1 TPS <1% group not presented because of small patient numbers (n=12).
†PD-L1 TPS was unknown in 53 patients.
The investigator-reported ORR was 41.6% (95% CI, 31.9-51.8) in treatment-naïve patients and 22.9% (95% CI, 19.1-27.1) in previously treated patients. Median DOR was 16.8 months (range, 2.1+ to 55.7+) and 38.9 months (range, 1.0+ to 71.8+), respectively.
Among the 60 patients who received two or more years of treatment with KEYTRUDA, the five-year OS rate was 78.6% in treatment-naïve patients and 75.8% in previously treated patients. The ORR in these patients was 86% and 91%, respectively. Median DOR was 52.0 months (range, 10.2 to 55.7+) in treatment-naïve patients and was not reached (range, 12.5 to 71.8+) in previously treated patients.
The safety profile of KEYTRUDA was consistent with what has been seen in previously reported studies among patients with advanced NSCLC. Treatment-related adverse events (TRAEs) of any grade occurred in 71% (n=388) of patients receiving KEYTRUDA; grade 3-5 TRAEs occurred in 13% (n=69) of patients. Immune-mediated adverse events were reported in 17% (n=92) of patients. Hypothyroidism was the most commonly reported immune-mediated adverse event, followed by pneumonitis, hyperthyroidism and skin toxicities.
“Five-year survival is a significant milestone for patients with advanced non-small cell lung cancer, and it is encouraging to see the long-term overall survival rates from our first KEYNOTE study,” said Dr. Roy Baynes, senior vice president and chief medical officer, Merck Research Laboratories. “These five-year data provide important insights into the long-term safety and efficacy of KEYTRUDA in patients with advanced non-small cell lung cancer.”
Additional Lung Cancer Data from KEYNOTE-189 (Abstract #9013)
New and updated data from the Phase 3 KEYNOTE-189 trial evaluating KEYTRUDA in combination with ALIMTA®(pemetrexed) and platinum (cisplatin or carboplatin) for the first-line treatment of metastatic nonsquamous NSCLC compared with pemetrexed plus platinum alone, will also be presented on Sunday, June 2 at ASCO (Abstract #9013). An updated analysis of the OS endpoint showed that after a median follow-up of 18.7 months (range, 0.2 to 30.9), KEYTRUDA in combination with pemetrexed-platinum chemotherapy reduced the risk of death by 44% compared with chemotherapy alone (HR=0.56 [95% CI, 0.45-0.70]; median OS 22.0 months vs. 10.7 months). An improvement in progression-free survival (PFS) was also observed, with a 52% reduction in the risk of progression or death compared with chemotherapy alone (HR=0.48 [95% CI, 0.40-0.58]; median PFS 9.0 months vs. 4.9 months). Fifty four percent of patients in the chemotherapy alone arm received subsequent immunotherapy, including 41% who received in-study crossover.
New findings at ASCO from KEYNOTE-189 also include the first-time presentation of the progression-free survival 2 (PFS2) study endpoint, a clinical endpoint used to assess the impact of next-line treatment on disease control, in the entire study population and different PD-L1 subgroups. Among patients who received KEYTRUDA in combination with chemotherapy, findings showed a 51% reduction in risk from time of randomization to objective tumor progression on next-line treatment or death from any cause, whichever comes first, compared with patients who received chemotherapy alone (HR=0.49 [95% CI, 0.40-0.59]; median PFS2 17.0 months vs. 9.0 months). Results were consistent across all three PD-L1 categories evaluated – with a 54% reduction in patients with a TPS <1% (HR=0.46 [95% CI, 0.33-0.66]), a 41% reduction in patients with a TPS of 1-49% (HR=0.59 [95% CI, 0.41-0.86]), and a 53% reduction in patients with a TPS ≥50% (HR=0.47 [95% CI, 0.33-0.69]).
Grade 3-5 adverse events from any cause occurred in 71.9% (n=291) of patients who received KEYTRUDA in combination with chemotherapy and 66.8% (n=135) in the chemotherapy alone arm. Adverse events leading to discontinuation of any treatment component occurred in 33.6% (n=136) of patients who received KEYTRUDA in combination with chemotherapy and 16.3% (n=33) in the chemotherapy alone arm. There were two deaths in the KEYTRUDA combination arm from immune-mediated adverse events and infusion reactions. KEYNOTE-189 was conducted in collaboration with Eli Lilly and Company, the makers of pemetrexed (ALIMTA®).
Study Design of KEYNOTE-001 (Abstract #LBA9015)
KEYNOTE-001 (ClinicalTrials.gov, NCT01295827) is a Phase 1b multicenter, open-label, multi-cohort trial evaluating KEYTRUDA in various advanced cancers, including 550 patients with either treatment-naïve or previously treated advanced NSCLC. Patients received 2 mg/kg or 10 mg/kg of KEYTRUDA every three weeks (Q3W) or 10 mg/kg of KEYTRUDA every two weeks until unacceptable toxicity or disease progression. The primary endpoint was ORR; secondary endpoints included PFS, OS and DOR.
Study Design of KEYNOTE-189 (Abstract #9013)
KEYNOTE-189 (ClinicalTrials.gov, NCT02578680) is a pivotal Phase 3, randomized, double-blind, placebo-controlled trial of 616 untreated patients with metastatic nonsquamous NSCLC and no EGFR or ALK genomic tumor aberrations designed to evaluate the efficacy of KEYTRUDA in combination with pemetrexed and cisplatin or carboplatin (n=410), compared with pemetrexed and cisplatin or carboplatin alone (n=206). Patients were randomized 2:1 to receive KEYTRUDA 200 mg, cisplatin or carboplatin, and pemetrexed intravenously Q3W for four cycles followed by KEYTRUDA 200 mg for up to 24 months and pemetrexed Q3W (n=410); or cisplatin or carboplatin and pemetrexed intravenously Q3W for four cycles followed by pemetrexed Q3W (n=206). Treatment continued until progression of disease or unacceptable toxicity. The dual primary endpoints were OS and PFS; secondary endpoints included ORR and DOR.
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 and breast cancers combined. The two main types of lung cancer are non-small cell and small cell. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 85% of all cases. Small cell lung cancer (SCLC) accounts for about 10 to 15% of all lung cancers. Between 2008 and 2014, the five-year survival rate for patients diagnosed in the U.S. with advanced NSCLC was only 5%. Moreover, approximately 50% of metastatic NSCLC patients in the U.S. will not receive second-line therapy.
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. There are currently more than 1,000 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.
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.
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 Twitter, Facebook, Instagram, YouTube and LinkedIn.
May 31, 2019