Abstract 1494P
Background
VEGF pathway and PD-1/PD-L1 axis blockade has shown benefit in various tumors. We decided to evaluate this therapeutic strategy in STS.
Methods
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.
Results
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.
Conclusions
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.
Clinical trial identification
NCT03475953.
Editorial acknowledgement
Legal entity responsible for the study
A. Italiano.
Funding
Bayer, Merck.
Disclosure
J. Guegan: Other, Institutional, Full or part-time Employment: explicyte. A. Bessede: Other, Institutional, Full or part-time Employment: explicyte. All other authors have declared no conflicts of interest.