Olaparib and durvalumab in patients with relapsed small cell lung cancer (MEDIOLA): An open-label, multicenter, phase 1/2, basket study

Introduction: Preclinical studies have demonstrated increased efficacy with combined DNA damage response inhibition and immune checkpoint blockade compared with either alone. We assessed olaparib in combination with durvalumab in patients with relapsed small cell lung cancer (SCLC). Methods: Patients with previously treated limited or extensive-stage SCLC received oral olaparib 300 mg twice daily, as run-in for 4 weeks, then with durvalumab (1500 mg intravenously every 4 weeks) until disease progression. Primary endpoints were safety, tolerability, and 12-week disease control rate (DCR). Secondary endpoints included 28-week DCR, objective response rate (ORR), duration of response, progression-free survival, overall survival, change in tumor size, and programmed death-ligand 1 (PD-L1) expression subgroup analyses. Results: Forty patients were enrolled and analyzed for safety; 38 were analyzed for efficacy. Eleven patients (28.9% [90% confidence interval (CI), 17.2–43.3]) had disease control at 12 weeks. ORR was 10.5% (95% CI, 2.9–24.8). Median progression-free and overall survival were 2.4 (95% CI, 0.9–3.0) months and 7.6 (95% CI, 5.6–8.8) months, respectively. The most common adverse events (≥40.0%) were anemia, nausea, and fatigue. Grade ≥ 3 adverse events occurred in 32 patients (80.0%). PD-L1 levels, tumor mutational burden, and other genetic mutations were evaluated, but no significant correlations with clinical outcomes were observed. Conclusions: Tolerability of olaparib with durvalumab was consistent with the safety profile of each agent alone. Although the 12-week DCR did not meet the prespecified target (60%), four patients responded, and median overall survival was promising for a pretreated SCLC population. Further analyses are required to identify patients most likely to benefit from this treatment approach.