FDA Grants Pembrolizumab Priority Review for TMB-High Tumors
April 07, 2020 04:24pm
By Lisa Astor
Pembrolizumab demonstrated an improvement in progression-free survival in the first-line treatment of patients with microsatellite instability-high or mismatch repair deficient unresectable or metastatic colorectal cancer, meeting one of the primary end points of the phase III KEYNOTE-177 trial.
Pembrolizumab (Keytruda) demonstrated an improvement in progression-free survival (PFS) in the first-line treatment of patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic colorectal cancer (CRC), meeting one of the primary end points of the phase III KEYNOTE-177 trial, according to a press release from Merck.
A statistically significant and clinically meaningful improvement in PFS was found with the use of pembrolizumab in comparison with chemotherapy by independent data monitoring committee review at the interim analysis.
The safety profile in the study was found to be consistent with the known toxicities for pembrolizumab from previous studies and no new safety signals were reported.
The data monitoring committee recommended that the trial continue without any changes toward the second co-primary end point of overall survival (OS).
“These head-to-head data with Keytruda are the first time a single-agent, anti-cancer therapy, and particularly an antiPD-1 monotherapy, achieved a statistically significant improvement in progression-free survival over chemotherapy, including the current standard of care regimen of mFOLFOX6 plus bevacizumab, in patients with MSI-H colorectal cancer,” said Roy Baynes, MD, PhD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, in the press release. “These data in the first-line treatment setting provide further evidence of the benefits of Keytruda monotherapy in patients whose tumors are MSI-H or dMMR. We look forward to sharing these data as quickly as possible with the medical community and regulatory authorities.”
KEYNOTE-177 is a randomized, open-label phase III trial exploring the use of pembrolizumab versus standard therapy for the treatment of patients with MSI-H or dMMR metastatic CRC (NCT02563002). A total of 308 patients were enrolled in the study.
Standard-of-care chemotherapy consisted of investigator’s choice between 1 of 6 treatment regimens: mFOLFOX6 (oxaliplatin, fluorouracil [5-FU], and folinic acid), mFOLFOX6 with cetuximab (Erbitux), mFOLFOX6 with bevacizumab (Avastin), FOLFIRI (irinotecan, fluorouracil, and folinic acid), FOLFIRI with cetuximab, or FOLFIRI with bevacizumab.
In the investigational arm, pembrolizumab was administered at a fixed dose of 200 mg every 3 weeks for up to 35 cycles or approximately 2 years.
Eligible patients were required to have an ECOG performance status of 0 or 1, measurable disease, and a life expectancy of at least 3 months. Those who had received prior systemic therapy, have active autoimmune disease, immunodeficiency requiring steroids, recent radiation therapy, active central nervous system metastases, another malignancy, HIV or hepatitis B or C virus, interstitial lung disease, active tuberculosis, or other active infections were not able to be enrolled in the trial.
The co-primary end points of the trial are PFS and OS; the secondary outcome measure is the overall response rate.
Approximately 10% to 15% of patients with CRC are expected to have tumors with MSI-H or dMMR.
Pembrolizumab was approved by the FDA for the treatment of previously treated patients with MSI-H or dMMR solid tumors in May 2017, and the antiPD-1 antibody also has many other tumor-specific indications.
Merck Announces KEYTRUDA® (pembrolizumab) Significantly Improved Progression-Free Survival as First-Line Treatment for Advanced Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Colorectal Cancer [news release]. Kenilworth, NJ: Merck; April 2, 2020.https://bit.ly/2JDwL3e. Accessed April 3, 2020.