A phase II multi-arm study of durvalumab and tremelimumab for advanced or metastatic sarcomas.

Abstract

11509 Background: The combination of durvalumab (D), (anti- PD-L1) and tremelimumab (T), (anti-CTLA-4), was evaluated to determine activity in specific sarcoma subtypes (NCT02815995). We report final results of the clinical efficacy, safety and correlatives. Methods: Pts ≥12 yrs, with advanced/metastatic sarcoma, were enrolled based on subtype: LPS, LMS, angiosarcoma (AS), UPS, synovial sarcoma, osteosarcoma, ASPS, chordoma, and other sarcomas. Pts received D 1500mg and T 75mg every 4 wks for 4 cycles followed by D alone every 4 wks for up to 12 months (mo) unless the patients experienced unacceptable toxicity or disease progression. Re-treatment was allowed if progression occurred after stopping therapy within the next 12 mo. The primary end-point was PFS at 12 wks (RECIST). Secondary objectives included safety, response rates (irRC and RECIST) and survival. Biopsies were collected at baseline and at 6 wks for flow, PD-L1, multiplex IHC staining and sequencing. Results: Baseline characteristics of the 57 pts who received treatment are listed in the Table. Median OS for all pts was 20.8 mo (95% CI: 11.7, NR), the 12-mo survival was 63% (95% CI: 52%, 78%) and the 24-mo survival was 45% (95%CI: 33%, 61%). The mPFS for all pts was 4.5 mo (95% CI: 2.8, 6.9). The PFS at 12 wks for all pts was 51% (95%CI: 37%, 63%), PFS at 12 mo was 28% (95% CI: 18%, 43%), and PFS at 24 mo was 25% (95% CI: 16%, 41%). The 12 wk PFS was lowest for the LPS cohort (6 pts) at 16% (95% CI: 1%, 52%), and highest for the ASPS cohort (10 pts) at 90% (95% CI: 47%, 99%). PRs by irRC were observed in ASPS (5/10), chordoma, (1/5), UPS (1/5), and cutaneous AS (1/1), and 14 pts completed 12 mo of therapy. 14 pts (24.6%) experienced grade ≥3 related AEs (colitis, nausea, cardiac dysfunction, thyroiditis, pneumonitis, hepatitis, myositis, anemia and fatigue). Clinical benefit correlated with tumors with an inflamed phenotype; based on higher than median density of 3 major categories of tumor infiltrating lymphocytes (TIL): CD3+, CD3+CD8+, CD3+CD8+GZB+, seen in the 36 paired biopsies. Conclusions: In addition to histology (ASPS, cutaneous AS, UPS, chordoma), a higher TIL immune score can help predict clinical benefit. Clinical trial information: NCT02815995 . [Table: see text]