1922P - Immunosarc II master trial: phase II of sunitinib and nivolumab in vascular sarcomas cohort - A GEIS, ISG and UCL study

Background

Advanced angiosarcoma comprises an aggressive sarcoma subset that exhibits poor prognosis and short-term duration of responses. Series treated with anthracyclines or taxanes reported an mPFS that ranged from 2.7 to 3.7 m. A trial with sorafenib reported a mPFS of 1.8 and 3.8 m, 6-m-PFSr of 25% and 31% (9m-PFSr of 0 and 3.8%), ORR of 15 and 13% and mOS of 9 and 12 m, for superficial and visceral cohorts respectively. As IMMUNOSARC I master-trial exploring sunitinib (S) plus nivolumab (N) in sarcoma detected signal of activity in angiosarcoma patients, a specific cohort of vascular sarcomas was designed as phase II trial in IMMUNOSARC II (NCT03277924).

Methods

Advanced, recently progressing, measurable and centrally reviewed vascular sarcomas (angiosarcoma, intimal sarcoma and epithelioid hemangioendothelioma) were enrolled and treated with S: 37.5 mg/d in first 14 days, then continued with 25 mg/d, along with N 240 mg every 2 weeks up to progression or intolerance. Imaging tests were assessed every 8 weeks. The main endpoint was 6m-PFSr, and the statistical assumptions were obtaining a 6m-PFSr in at least 11 patients out of 23 patients, with H₀=30% and H₁=60% (α 0.05; β 0.10).

Results

Patients with angiosarcoma (17), EHE (6) and intimal sarcomas (3) were accrued from Oct. 2019 to Apr. 2023 in 8 centers from Spain, Italy and UK. Patients had a median age of 60 y (25-82), F=20/M=6 distribution and a median of previous lines of 2 (0-5). Median follow-up was 24 m (5.9-42.1). The 6m-PFSr was 45% (23-66) for 23 evaluable patients. Considering angiosarcoma patients, there were 5 (33%) PR, 7 (47%) SD and 3 (20%) PD out of 15 evaluable patients. The mPFS was 3.93 m and the 6m-PFSr was 36% (11-61). The mOS was 15.73 m (1.83-29.64). End-of-treatment reasons were PD 71%, toxicity 22% and doctor decision 7%. Most common grade 3-4 TREAEs were neutropenia (11.8%) and asthenia (11.8%).

Conclusions

S and N combination has demonstrated to be active in advanced vascular sarcomas. This activity favorably compares with that previously reported for sorafenib activity. Even though the outcome did not reach the H1, antiangiogenics and PD1 inhibitors deserve to be explored, maybe with other combinations, in vascular sarcomas.

Clinical trial identification

NCT03277924.

Editorial acknowledgement

Legal entity responsible for the study

Spanish Group for Research on Sarcoma (GEIS).

Funding

Pfizer and BMS.

Disclosure

J. Martinez Trufero: Financial Interests, Personal, Advisory Board, Advisory Board meeting: PharmaMar, Eisai; Financial Interests, Personal, Invited Speaker: Roche, Eisai, Merck, Medicamenta, MSD, Ipsen; Financial Interests, Personal, Advisory Board, Advisory Board Meeting: GSK, Deciphera, Boehringer Ingelheim, Eisai; Financial Interests, Institutional, Local PI, Clinical trial: RAIN Therapeutics, Blueprint, Lilly, Kariopharm Therapeutics, Syneos Health, Boehringer Ingelheim, Ayala Pharmaceuticals, SynOx Therapeutics; Non-Financial Interests, Member of Board of Directors, Spanish group of Sarcoma Research: GEIS Group; Non-Financial Interests, Member of Board of Directors, Spanish Group of Head and Neck cancer Research: TTCC Group. S. Strauss: Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board, medical advisor: Ceridwen Oncology. S. Stacchiotti: Financial Interests, Personal, Advisory Board: Bayer, Bavarian Nordic, Daiichi Sankyo, Novartis, Ikena, Astex Pharmaceuticals, Rain Therapeutics; Financial Interests, Personal, Invited Speaker: GSK, PharmaMar, Aadi; Financial Interests, Personal, Advisory Board, Advisory board meeting: Agenus; Financial Interests, Personal, Advisory Board, Advisory board meetings: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker, Lectures: Gentili; Financial Interests, Personal, Advisory Board, Advisory board: Servier; Financial Interests, Institutional, Local PI: Advenchen, Deciphera, Epizyme, Daiichi Sankyo, GSK, Karyopharm, PharmaMar, SpringWorks, Hutchison MediPharma International Inc, Inhibrix; Financial Interests, Institutional, Coordinating PI: Bayer; Financial Interests, Institutional, Funding: Blueprint, Novartis; Non-Financial Interests, Member of Board of Directors, Secretary: Connective Tissue Oncology; Non-Financial Interests, Advisory Role: Chordoma Foundation, Epithelioid Haemangiondothelioma Foundation , Desmoid Foundation , Epithelioid Hemangioendothelioma (EHE) Rare Cancer Charity (UK); Non-Financial Interests, Other, Secretary: EORTC soft tissue and bone sarcoma group; Non-Financial Interests, Leadership Role, President: Italian Sarcoma Group. D. Da Silva Moura: Financial Interests, Personal, Other, Travel: Pfizer. J. Martin-Broto: Financial Interests, Personal, Advisory Board, Honoraria: Lilly, PharmaMar, Eisai, Bayer, Roche, Boehringer Ingelheim, Amgen; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Personal, Advisory Board, Speaker: Tecnofarma, Asofarma; Financial Interests, Institutional, Coordinating PI: PharmaMar, Eisai, Novartis, IMMIX Biopharma, Lixte, Karyopharm, Bayer, Celgene, Pfizer, BMS, Lilly; Financial Interests, Institutional, Local PI: Blueprint, Deciphera, Nektar, Forma, Amgen, Daiichi Sankyo, Arog, Adaptimmune, GSK, Ran Therapeutics, Inhibrx, Ayala Pharmaceuticals, Philogen, Cebiotex, PTC Therapeutics, Inc. and SpringWorks therapeutics. All other authors have declared no conflicts of interest.