FDA Accepts Application for Pembrolizumab as Adjuvant Therapy for Stage 1B-3A Non-Small Cell Lung Cancer Following Complete Surgical Resection

The FDA has accepted a new supplemental Biologics License Application (sBLA) seeking approval for pembrolizumab (Keytruda; Merck) for the adjuvant treatment of patients with stage 1B, 2, or 3A non-small cell lung cancer (NSCLC) following complete surgical resection, according to a Merck press release.

Pembrolizumab (100 mg) is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the immune system to hunt and fight tumor cells. The drug is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which activates T lymphocytes that may affect both tumor cells and healthy cells.

The sBLA is based on data from the phase 3 KEYNOTE-091 trial, which had dual primary endpoints of disease-free survival (DFS) regardless of PD-L1 expression and DFS in patients whose tumors express PD-L1. The study randomized 1177 patients to receive either pembrolizumab or placebo, with the median number of doses at 17 for pembrolizumab and 18 for placebo.

Adjuvant treatment with pembrolizumab demonstrated a significant improvement in DFS for patients regardless of PD-L1 expression compared to placebo. Additionally, DFS in patients whose tumors express PD-L1 did not reach statistical significance per the pre-specified statistical plan.

“Keytruda is foundational in the treatment of metastatic non-small cell lung cancer. The acceptance of our application demonstrates the progress we are making in earlier lines and earlier stages of certain cancers across our oncology portfolio,” said Eliav Barr, MD, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, in the press release. “If approved, Keytruda would be the first adjuvant immunotherapy-based option in the US for patients with stage IB (≥4 centimeters) to IIIA non-small cell lung cancer following surgical resection regardless of PD-L1 expression.”

There are 6 other trials evaluating a pembrolizumab-based regimen in patients with earlier stages of cancer met their primary endpoints, which include KEYNOTE-716 in stage IIB and IIC melanoma; KEYNOTE-054 in stage III melanoma; KEYNOTE-564 in renal cell carcinoma; KEYNOTE-522 in triple-negative breast cancer; KEYNOTE-629 in cutaneous squamous cell carcinoma; and KEYNOTE-057 in Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer.

REFERENCE

FDA Accepts Application for Merck’s KEYTRUDA® (pembrolizumab) as Adjuvant Therapy for Stage IB (≥4 centimeters)-IIIA Non-Small Cell Lung Cancer Following Complete Surgical Resection. June 13, 2022. Accessed June 14, 2022. Merck. https://www.merck.com/news/fda-accepts-application-for-mercks-keytruda-pembrolizumab-as-adjuvant-therapy-for-stage-ib-%e2%89%a54-centimeters-iiia-non-small-cell-lung-cancer-following-complete-surgical-resecti/