1494P Regomune - a phase II study of regorafenib + avelumab in solid tumors: Results of the soft tissue sarcoma (STS) cohort

VEGF pathway and PD-1/PD-L1 axis blockade has shown benefit in various tumors. We decided to evaluate this therapeutic strategy in STS. This is a single-arm open-label multicentric phase II trial assessing the efficacy and safety of regorafenib (R) (160 mg QD 3weeks/4) + avelumab (A) (10 mg/kg every 2 weeks) combination in advanced STS patients (pts). All pts had to progress at inclusion, based on central review of 2 imaging obtained at less than a 6 month interval. The primary endpoint was the objective response rate (ORR), based on central review according to RECIST 1.1. Secondary endpoints included: 1-year progression free survival (PFS), 1-year overall survival (OS), and safety using NCI-CTCAE v5.0. Correlative studies were planned from pts tumor samples obtained at baseline. Between May 2019 and August 2021, 49 STS pts were enrolled in 5 centers : 22 (45%) leiomyosarcoma, 9 (18%) synovialosarcoma, 4 (8%) liposarcoma, 4 (8%) undifferentiated pleomorphic sarcoma and 10 (21%) others subtypes. Median age was 57.1 (range 21 – 81). Number of previous treatment lines was: 2 (range 1 – 7). 11 (22.4%) pts had previously received an antiangiogenic drug (AA). 41 (84%) pts experienced at least 1 dose modification or treatment interruption due to R and/or A. The most common grade 3/4 adverse events were : Palmo-plantar erythrodysesthesia (12.2% of pts), fatigue (10.2%), diarrhea (10.2%). No death was related to the treatment. Median follow-up was 7.1 months. Among the 43 pts who had at least one imaging tumor assessment, 4 (9.3%) achieved a partial response, 17 (39.5%) demonstrated a stable disease and 22 (51.2%) had a progressive disease. 14 (32.6%) had tumor shrinkage. The median duration of response was 7.8 months (95% CI: 3.8-NA). 6-month PFS was 22.1% (95% CI: 11% – 35.7%). The median PFS and OS were 1.8 months (95%CI: 1.7 – 3.5) and 15.1 months (95%CI: 7.2 – NA) respectively. The ORR observed with the R + A combo was similar to other combinations of AA with PD1 monoclonal antibodies investigated in advanced STS pts (excluding alveolar subtype). The 6-months PFS is higher than the 14% non-progression rate proposed by EORTC to suggest drug activity (Van Glabbeke et al, 2002). Biomarker analyses will be presented at the meeting.