According to the results of a molecularly matched, tumor-agnostic phase II trial, the combination of the PARP inhibitor olaparib and the PD-1 inhibitor pembrolizumab demonstrated antitumor activity with no new safety signals, particularly in patients with BRCA1/2 mutations. Data from this KEYLYNK-007 trial were presented by Timothy Yap, MBBS, PhD, Professor of Investigational Cancer Therapeutics and Vice President and Head of Clinical Development in the Therapeutics Discovery Division of The University of Texas MD Anderson Cancer Center, at the 2025 American Association for Cancer Research (AACR) Annual Meeting (Abstract CT004).
“Previous studies suggested this combination was likely to have synergistic effects, and that’s what we saw in this trial,” Dr. Yap stated. “We demonstrated durable antitumor activity, particularly in the subset of patients with BRCA1/2 mutations across multiple different solid tumors, which goes beyond the currently approved indications for these therapies.”
Study Details and Results
The trial enrolled 332 patients with 30 different cancer types, according to three different genetic alteration groups defined in advance: patients with BRCA1/2 mutations (n =132), those with non-BRCA1/2 homologous recombination repair (HRR) mutations (n = 104), and those with homologous recombination deficiency (HRD; n = 96).
A total of 18 patients had a complete response to this treatment as determined by radiologic imaging, with 11 of them in the BRCA1/2 mutation subgroup. Responses were seen in multiple tumor types for which these therapies are not currently approved. The median duration of response was highest in the BRCA1/2 mutation subgroup, at 19.1 months (95% confidence interval = 10.7 months to not reached). The disease control rate was more than 60% in all three subgroups. The median follow-up was 13.4 months in the BRCA1/2 mutation group, 10.4 months in the HRR mutation group, and 10.8 months in the HRD group.
The safety profile was consistent with the known safety profiles of both therapies.
“It’s notable that this trial represents the largest data set of molecularly matched patients for this combination therapy,” Dr. Yap said. “We hope further analysis of these data can help identify new predictive biomarkers to better identify patients likely to have exceptional responses to this combination.”
Disclosure: Funding for this study was provided by Merck Sharp & Dohme. For full disclosures of all study authors, visit abstractsonline.com.
