The FDA has accepted a new regulatory submission for ancillary biologics for pembrolizumab, an anti-PD-1 therapy, as a single agent for the treatment of patients with advanced endometrial cancer with high microsatellite instability or mismatch repair deficiency who have disease progression, previous systemic Therapy in any setting and are not candidates for curative surgery or radiation.
The FDA has accepted a new approval application for supplementary biologics (sBLA) for pembrolizumab (Keytruda), an anti-PD-1 therapy, as a single agent for the treatment of patients with advanced endometrial cancer with high microsatellite instability (MSI-H.) Or Mismatch- Repair deficiencies (dMMR) that show disease progression after prior systemic therapy in any setting and are not candidates for curative surgery or radiation, according to a Merck press release.1
The sBLA is based on the results of Cohorts D and K of the KEYNOTE-158 study (NCT02628067), which investigated pembrolizumab monotherapy in participants with advanced solid tumors. The Phase 2, non-randomized, interventional study with parallel assignment had an estimated enrollment of 1,595 participants with an expected completion date in June 2026. The primary endpoint of the study is objective response rate (ORR). Secondary endpoints are duration of response (DoR), progression-free survival (PFS), and overall survival (OS).2
During the ongoing study, patients will receive either 200 mg or 400 mg of pembrolizumab. Solid tumors included in the study include advanced cancer, anal cancer, anal cancer, biliary cancer, cholangiocarcinoma, biliary tract cancer, neuroendocrine tumor, carcinoid tumor, endometrial cancer, endometrial cancer, cervical cancer, cervical cancer, salivary cancer, salivary cancer, cell cancer, small cancer, vulvar cancer , Salivary gland cancer, salivary gland cancer, parotid cancer, advanced solid tumors and colorectal cancer.
To be able to participate in the study, patients must have made progress in therapy with known clinical benefit or intolerance to therapies, have a radiologically measurable disease, have an ECOG status of 0 or 1, a life expectancy of at least 3 months, and must have adequate organ function be ready to offer adequate contraception. Patients with a diagnosed immune deficiency, autoimmune disease, treatment with a monoclonal anti-cancer antibody within 4 weeks prior to study day 1, active infections or known active metastases of the central nervous system are not eligible.
“The acceptance of our application by the FDA adds to our momentum to develop new treatment options for the most difficult cancers in women,” said Scot Ebbinghaus, MD, vice president of clinical research at Merck Research Laboratories, in a press release. “Keytruda monotherapy already plays a role in the treatment of certain patients with advanced endometrial cancer through the tumor-agnostic indication MSI-H, which received accelerated approval four years ago. We look forward to presenting the latest KEYNOTE-158 results, including updated data for Keytruda in certain types of advanced MSI-H / dMMR endometrial cancer, at the ESMO Congress in September. “
In July 2021 the FDA grants approval for pembrolizumab in combination with lenvatinib (Lenvima). The combination resulted in a median OS of 17.4 months in patients with MMR-competent (pMMR) disease compared to 12 months with chemotherapy. For all patients, the median OS was 18.3 months for the combination compared to 11.4 months with chemotherapy.
The median PFS for the combination was 6.6 months for patients with pMMR and 7.2 months for the total population. In patients receiving chemotherapy, the median PFS was 3.8 months in those with pMMR disease and 3.8 months in the general population. The ORR for the combination in patients with pMMR disease was 30.3% versus 15.1% in those receiving the combination. The complete response rate was 5.2% in the combination cohort versus 2.6% in the chemotherapy cohort.