On April 2, Merck & Co., Inc. announced that the Phase III KEYNOTE-177 study of Keytruda as first-line monotherapy for patients with unresectable or metastatic colorectal cancer characterized by high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR) had met one of its composite primary endpoints, demonstrating a significant improvement in progression-free survival (PFS) compared to the control group.
The KEYNOTE-177 study is the first global Phase III clinical trial to conduct a “head-to-head” evaluation of the efficacy and safety differences between monotherapy as a first-line treatment and standard-of-care chemotherapy regimens in patients with MSI-H/dMMR colorectal cancer. The KEYNOTE-177 study employed a randomized, open-label design and enrolled 308 patients, who received either Keytruda (200 mg every 3 weeks for up to 35 cycles) or investigator’s choice of chemotherapy regimens, including mFOLFOX6, mFOLFOX6 plus bevacizumab, mFOLFOX6 plus cetuximab, FOLFIRI, FOLFIRI plus bevacizumab, or FOLFIRI plus cetuximab. The study had dual primary endpoints of progression-free survival (PFS) and overall survival (OS), with the objective response rate (ORR) as a secondary endpoint.
Based on the results of an interim analysis conducted by the independent Data Monitoring Committee (DMC), Keytruda monotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with investigator’s choice of standard chemotherapy. In accordance with the DMC’s recommendation, the study will continue to evaluate the other primary endpoint, overall survival (OS). The safety profile of Keytruda in the KEYNOTE-177 study was consistent with that reported in previous studies, with no new safety signals identified.
On May 24, 2017, Keytruda received accelerated approval from the U.S. Food and Drug Administration (FDA) for the treatment of previously treated unresectable or metastatic solid tumors with microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR), becoming the first “tissue-agnostic” anticancer drug approved globally based on biomarkers rather than tumor origin. These two biomarkers are commonly found in colorectal cancer, endometrial cancer, and gastric cancer, and are also present in a minority of cases of other cancers, including breast cancer, prostate cancer, bladder cancer, and thyroid cancer.
Colorectal cancer is the third most commonly diagnosed cancer globally and the second leading cause of cancer-related deaths. It is estimated that in 2018, there were nearly 850,000 new cases of colorectal cancer and 880,000 deaths worldwide. In the United States, there were nearly 150,000 new cases of colorectal cancer, with more than 53,000 patients dying from the disease in 2020. Statistics show that approximately 10% to 15% of colorectal cancer patients carry MSI-H or dMMR.
Dr. Roy Baynes, Senior Vice President and Head of Global Clinical Development at MSD, stated, “The head-to-head data from the KEYNOTE-177 study mark the first time a monotherapy has demonstrated superior efficacy compared to standard-of-care chemotherapy regimens (including mFOLFOX6 plus bevacizumab) as first-line treatment for patients with MSI-H/dMMR colorectal cancer. This further substantiates the therapeutic potential of Keytruda monotherapy in patients with MSI-H or dMMR tumors. We look forward to sharing these data with the medical community and regulatory authorities as soon as possible.”