Merck scores new advance on tumor-agnostic front as Keytruda beat chemo-based regimens in a type of colorectal cancer
Back in 2017, before the term “tumor agnostic” really took hold among cancer drug developers, Merck became the first to secure such an approval for Keytruda as a second-line treatment for patients characterized by a biomarker — rather than where the cancer started in the body. Now it’s looking to break fresh ground with a new slate of data suggesting the drug’s utility in the frontline setting for colorectal cancer.
Today’s data come from an interim analysis of KEYNOTE-177, which compared Keytruda to a number of chemotherapy-based regimens of choice. Topline results indicate the PD-1 drug met one of the dual primary endpoints: progression-free survival. The other, overall survival, is still being studied.
All 308 patients in the Phase III trial have stage IV colorectal carcinoma confirmed to be advanced microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). Microsatellites are short, repeated sequences of DNA. When they appear in different sizes as the germline DNA, it signals a defect in the ability to repair mistakes that occur when DNA is being copied.
Around 10% to 15% of colorectal cancer patients have tumors that fit the description, Merck noted.
Roy Baynes, CMO of Merck Research Laboratories, emphasized that the head-to-head data represent a historic feat for the PD-1: It’s the first time a single-agent therapy achieved a statistically significant improvement in PFS over chemo, “including the current standard of care regimen of mFOLFOX6 plus bevacizumab, in patients with MSI-H colorectal cancer,” he said.
Mizuho analyst Mara Goldstein continues to cheer Merck on, noting that there’s a lack of available therapies in colorectal cancer beyond chemo plus Erbitux or Avastin.
“This is the third trial thus far with a dual PFS/OS endpoint that has reached PFS on interim and is continuing to an OS readout, which we see as skewing future OS readouts to the upside through 2021,” she added.
The other two are KEYNOTE-355 in first-line PD-L1 positive triple-negative breast cancer and KEYNOTE-204 in relapsed/refractory classical Hodgkin lymphoma.
A PFS win, though, doesn’t guarantee success on the OS front, as the painful setback in KEYNOTE-604 (extensive-stage small cell lung cancer, or ES-SCLC) showed. How the FDA — which was demonstrably upbeat when waving through Keytruda’s first MSI-H OK — will handle that kind of situation remains to be seen.