Safety and activity of Combined AVElumab with Axitinib in unresectable or metastatic Thymomas B3 and Thymic carcinomas: The CAVEATT study.

Abstract

e21114 Background: Patients (pts) with advanced B3 thymoma (B3T) and thymic carcinoma (TC) resistant to chemotherapy have limited treatment options. Treatment with Anti-PD1 showed not negligible toxicity and limited activity, and anti-VEGFR drugs obtained limited and short lasting antitumor responses. No data on combined anti-PD1/PD-L1 with antiangiogenic drugs are available in B3T/TC. We report preliminary results on safety and activity of avelumab combined with axitinib in this pts population. Methods: The CAVEATT is a single arm, multicentric, phase II trial in immunotherapy-naive pts with advanced B3T or TC, progressing after at least one line of platinum based chemotherapy. Prior therapy with antiangiogenic drugs is allowed. Pts received Avelumab 10 mg/kg iv every 2 weeks and Axitinib 5 mg twice a day until progression or toxicity. The primary objective of the study is overall response rate (ORR) by RECIST 1.1; secondary endpoints include ORR by irRC and ITMIG, and QoL by EORTC QLQ-C30. An interim futility analysis is planned after the enrollment of the first 18 patients. If at least 5 out of 18 patients will obtain a PR, the accrual will continue to reach the total number of 33 pts, according with a Simon’s minimax design. Tumor and blood samples are collected at baseline and whenever feasible at disease progression, to identify predictive biomarkers of response and mechanisms of resistance to treatment. Results: 1 pt with B3T and 12 with TC were enrolled from April 2019 to January 2020. Median age was 59 years (range 33-77). 8 pts received ≥2 previous line of therapies, and 6 pts were pretreated with an antiangiogenic drug. The median follow-up was 5.1 months. 10 pts were evaluable for response. The proportions of patients who achieved a partial response (PR) or a stable disease (SD) were respectively 40% (95% CI 17%–69%) and 60% (95% CI 30%–83%). The median PFS was 7.9 months (95% CI 2.5–NA) 12 pts were evaluable for toxicity. Treatment-related adverse events (AE) of grade 1 or 2 occurred in 7 (58%) pts, and the most common was diarrhea (3 pts). Grade ≥3 AEs occurred in 2 (17%) pts: 1 had G3 hyperthension and 1 G3 hand foot syndrome, both leading to axitinib drug reduction. No immune-related AEs (irAEs) were observed. No patient stopped treatment for toxicity, 5 pts stopped for progressive disease, and 8 pts are still on treatment. Conclusions: Preliminary results suggest promising antitumor activity and a good toxicity profile of the combination of axitinib and avelumab in pts with advanced B3T and TC. Accrual is ongoing to reach the target of 33 pts Clinical trial information: 2017-004048-38 .