Pembrolizumab Plus Olaparib Falls Short in Phase 3 Study When Used First Line in Metastatic, Nonsquamous NSCLC

Use of the PD-1 inhibitor pembrolizumab (Keytruda) with olaparib (Lynparza), a poly ADP ribose polymerase (PARP) inhibitor, failed to meet the dual primary end points of a phase 3 study evaluating this combination in first-line treatment of certain patients with metastatic nonsquamous non–small cell lung cancer (NSCLC).

An update on the trial, KEYLYNK-006 (NCT03976323), was announced today by Merck, maker of pembrolizumab. Olaparib was developed by Merck and AstraZeneca.

The trial enrolled an estimated 1005 patients in the induction phase and randomized 672 patients with a complete or partial response or with stable disease. Results did not meet the study’s prespecified criteria for overall survival (OS) or progression-free survival (PFS) compared with pembrolizumab combined with chemotherapy (pemetrexed plus carboplatin or cisplatin), followed by pembrolizumab plus maintenance chemotherapy (pemetrexed).

Secondary end points included assessments for safety and health-related quality of life assessments. Safety results for pembrolizumab and olaparib were consistent with those seen in prior studies of the individual therapies, according to Merck’s statement. “A full evaluation of the data from this study is ongoing,” the statement said. “Merck will work with investigators to share the results with the scientific community.”

“As lung cancer continues to be the leading cause of cancer death worldwide, we are committed to exploring [pembrolizumab]-based combinations and novel candidates that may further help improve patient outcomes,” Gregory Lubiniecki, MD, vice president, global clinical development, Merck Research Laboratories, added in the statement. “These results are an important reminder of how challenging it may be to treat these patients with metastatic nonsquamous [NSCLC]. We sincerely thank the patients and investigators for their important contributions to this study.”

In December 2023, Merck stopped the KEYLYNK-008 trial (NCT03976362), a separate phase 3 study involving pembrolizumab (Keytruda) with olaparib, but in patients with metastatic squamous NSCLC. The combination also missed end points in OS and PFS in triple-negative breast cancer presented at the San Antonio Breast Cancer Symposium that month. Other trials involving pembrolizumab and olaparib are studying the combination in stage III NSCLC and in prostate cancer.