The US FDA approved Keytruda (pembrolizumab) and Keytruda QLEX (pembrolizumab and berahyaluronidase alfa-pmph) in combination with paclitaxel and bevacizumab for adult patients with platinum-resistant ovarian carcinoma (PROC) with PD-L1 expressing tumors. As announced by Merck & Co., the decision means Keytruda is the first immunotherapy-based regimen approved specifically for second- or third-line PROC.

The approval covers both the traditional intravenous (IV) formulation and the newer subcutaneous (SC) formulation of the PD-1 inhibitor (Keytruda QLEX). For the IV route, pembrolizumab is administered at a fixed dose of 200 mg every three weeks or 400 mg every six weeks. The SC formulation is administered every three weeks. Patient eligibility is restricted to those with platinum-resistant disease who have received no more than two prior systemic lines of therapy and whose tumors are confirmed as PD-L1 positive by FDA-approved test. The sBLA application was granted priority review by the FDA, following on from a previous orphan drug designation in ovarian cancer.

Clinical evidence supporting the approval was derived from the Phase III KEYNOTE-B21 trial, a randomized, double-blind study. the trial evaluated the efficacy of adding pembrolizumab to a chemotherapy backbone of paclitaxel and bevacizumab versus chemotherapy and bevacizumab alone. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The company reported that the pembrolizumab combination demonstrated a statistically significant improvement in PFS compared to the control arm. Safety data were consistent with the known profiles of the individual agents, with immune-mediated adverse events monitored as part of the standard pembrolizumab safety protocol.

Approval context

Platinum-resistant ovarian cancer has historically been associated with poor prognoses and limited treatment options, with the standard of care often relying on single-agent chemotherapy or bevacizumab combinations. While pembrolizumab is already approved for over 30 indications, including certain MSI-H or dMMR solid tumors, this represents its first specific indication for ovarian carcinoma.

The new indication follows recent advancements in the field, such as the 2022 approval of the antibody-drug conjugate Elahere (mirvetuximab soravtansine-gynx) for folate receptor alpha-positive PROC. The PROC development landscape is increasingly crowded. Other innovative drugs in development for this indication include the antibody-drug conjugate upifitamab rilsodotin by Mersana Therapeutics, which targets NaPi2b and is in late-stage clinical evaluation. Additionally, AstraZeneca and Merck are investigating the PARP inhibitor Lynparza (olaparib) in various combination settings, while GSK is evaluating the PD-1 inhibitor Jemperli (dostarlimab) in Phase III trials for gynecologic malignancies.