Clinical activity of pembrolizumab (P) in undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated/pleomorphic liposarcoma (LPS): Final results of SARC028 expansion cohorts.

11015 Background: Immune checkpoint inhibitors have demonstrated activity in multiple tumor types but their activity in soft tissue sarcomas remains limited. In the multicenter phase II study, SARC028, the anti-PD-1 antibody, P demonstrated objective responses that were largely restricted to UPS and LPS subtypes. We now report outcomes from 2 expansion cohorts of SARC 028 in advanced UPS and LPS. Methods: To further confirm the clinical activity of P in UPS and LPS, we enrolled an additional 30 pts in each of 2 expansion cohorts for a total of 40 UPS and 40 LPS pts. Primary endpoint was investigator-assessed response by RECIST v1.1. Secondary endpoints were safety, progression-free survival (PFS), 12-week PFS rate, and overall survival (OS). An ORR of 25% was considered clinically meaningful and < 10% was considered to show lack of efficacy. P was to be considered a success if 8 or more of 40 enrolled patients had a PR or better (1-sided α = 0.042, 82% power). Pts age ≥18 with advanced, refractory UPS or LPS received 200 mg of P IV every 3 weeks until progression or unacceptable toxicity. Results: Preliminary results from the first 10 pts in each of the UPS and LPS cohorts have been reported. We now present summary data after enrolling an additional 30 pts in each cohort. The ORR in the UPS cohort was 23% (9/40), with an additional 5/30 PRs observed in the expansion cohort (total 2 CRs, 7 PRs). In the LPS cohort, the ORR was 10% (4/39 evaluable pts), with an additional 2/30 PRs observed (total 4 PRs). Median PFS for the UPS group was 3 months 95% CI: 2, 5 and 2 months 95% CI: 2, 4 for the LPS group. 12-week PFS rate was 50% in UPS 95% CI: 35, 65 and 44% in LPS 95% CI: 28, 60. The UPS group had a median OS of 12 months 95% CI: 7, 34 and 13 months 95% CI: 8, NR for the LPS group. P was well tolerated with no unexpected toxicities. Conclusions: The UPS cohort achieved its primary endpoint, however the activity of P in UPS deserves further evaluation in a randomized study. The activity of P was not confirmed in the LPS cohort. Ongoing biomarker analyses may direct better patient selection and guide future combination strategies. Clinical trial information: NCT02301039.