May 28, 2020: “Merck known as MSD outside the United States and Canada, today announced the first presentation of results from KEYNOTE-177, a Phase 3 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, for the first-line treatment of patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic colorectal cancer.
In this pivotal study, KEYTRUDA monotherapy significantly reduced the risk of disease progression or death by 40% (HR=0.60 [95% CI, 0.45-0.80; p=0.0002]) and showed a median progression-free survival (PFS) of 16.5 months compared with 8.2 months for patients treated with chemotherapy
(investigator’s choice of mFOLFOX6 or FOLFIRI, with or without bevacizumab or cetuximab), a current standard of care in this patient population.
As previously announced, the study will continue without changes to evaluate overall survival (OS), the other dual primary endpoint.
These results were selected for presentation on Sunday, May 31, 2020 in the plenary session of the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #LBA4).
“For many years, the standard of care for the first-line treatment of patients with MSI-H colorectal cancer has been the combination of mFOLFOX6 plus bevacizumab.
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This is the first time a single-agent, anti-PD-1 therapy demonstrated a superior, statistically significant and clinically meaningful improvement in progression-free survival compared to chemotherapy for these patients,” said Dr Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories.
“There is an unmet need for new treatment options in the first-line setting that may provide sustained, long-term improvements in outcomes for patients with MSI-H colorectal cancer.
We are grateful to have the opportunity to present these practice-changing findings at the plenary session of this year’s ASCO.”
“KEYTRUDA monotherapy significantly reduced the risk of disease progression or death by 40% versus standard of care chemotherapy, with fewer treatment-related adverse events observed, in patients with MSI-H metastatic colorectal cancer.
KEYTRUDA also demonstrated a long-term, durable response that lasted over two years for those who responded to treatment,” said Thierry Andre, MD, professor of medical oncology, Sorbonne University, and Head of the Medical Oncology Department in St. Antoine Hospital, Assistance Publique Hôpitaux de Paris.
“Data from KEYNOTE-177 show that KEYTRUDA monotherapy has the potential to become the new standard of care for first-line treatment of patients with MSI-H metastatic colorectal cancer.”
In May 2017, KEYTRUDA became the first cancer therapy approved by the U.S. Food and Drug Administration for use based on a biomarker, regardless of tumor type, in previously treated patients with MSI-H or dMMR solid tumors.
As announced, more than 80 abstracts in nearly 20 types of solid tumors and blood cancers will be presented from Merck’s broad oncology portfolio and investigational pipeline at ASCO. A compendium of presentations and posters of Merck-led studies will be posted by Merck on Friday, May 29 at 8 a.m. ET. Follow Merck on Twitter via @Merck and keep up to date with ASCO news and updates by using the hashtag #ASCO20.
KEYNOTE-177 Study Design and Additional Data (Abstract #LBA4)
KEYNOTE-177 is a randomized, open-label, Phase 3 trial evaluating KEYTRUDA monotherapy versus standard of care chemotherapy for the first-line treatment of patients with MSI-H or dMMR metastatic colorectal cancer (ClinicalTrials.gov, NCT02563002).
The dual primary endpoints are PFS and OS. The study enrolled 307 patients, who were randomized to receive either KEYTRUDA (200 mg intravenously on Day 1 of each three-week cycle for up to 35 cycles) or investigator’s choice of one of the following chemotherapy-based regimens: mFOLFOX6; mFOLFOX6 plus bevacizumab (5 mg/kg IV on Day 1 of each two-week cycle); mFOLFOX6 plus cetuximab (400 mg/m2 IV, then 250 mg/m2 weekly in each two-week cycle); FOLFIRI; FOLFIRI plus bevacizumab (5 mg/kg IV on Day 1 of each two-week cycle); or FOLFIRI plus cetuximab (400 mg/m2 IV, then 250 mg/m2 weekly in each two-week cycle).
In this study, KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in PFS (HR=0.60 [95% CI, 0.45-0.80; p=0.0002]) and showed a median PFS of 16.5 months compared with 8.2 months for patients treated with chemotherapy. The two-year PFS rate was 48% with KEYTRUDA versus 19% with chemotherapy.
The ORR was 43.8% with KEYTRUDA versus 33.1% with chemotherapy, with a complete response observed in 11.1% and 3.9% of patients, respectively; partial responses were observed in 32.7% and 29.2% of patients, respectively.
The median duration of response was not reached with KEYTRUDA (range, 2.3+ to 41.4+) versus 10.6 months with chemotherapy (range, 2.8 to 37.5+). Additionally, 83% of patients had durable responses lasting at least two years with KEYTRUDA versus 35% with chemotherapy.
In the study, 59% of patients in the intent-to-treat population received subsequent anti-PD-1/PD-L1 therapy after discontinuing study treatment in the chemotherapy arm.
The safety profile of KEYTRUDA demonstrated a lower incidence of Grade ≥3 treatment-related adverse events (AEs) versus chemotherapy (22% versus 66%, respectively), and no new toxicities were observed.
Immune-mediated AEs and infusion reactions occurred in 31% of patients receiving KEYTRUDA and 13% of patients receiving chemotherapy.
The most commonly reported immune-mediated AEs were hypothyroidism (12%) and colitis (7%) with KEYTRUDA, and infusion reactions (8%) with chemotherapy.”
