A phase II multi-arm study of durvalumab and tremelimumab for advanced or metastatic sarcomas.
Neeta Somaiah, Anthony P. Conley, Heather Lin, Behrang Amini, Sharjeel Sabir, Dejka M. Araujo, Robert S. Benjamin, J. Andrew Livingston, Shreyaskumar Patel, Ravin Ratan, Vinod Ravi, Maria A. Zarzour, Wei‐Lien Wang, Taylor Tate, Christina L. Roland, Najat C. Daw, P. Andrew Futreal, Alexander J. Lazar, Ignacio I. Wistuba, Patrick Hwu
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]