Efficacy and safety of nivolumab plus ipilimumab for patients with pre-treated type B3 thymoma and thymic carcinoma: Results from the EORTC-ETOP NIVOTHYM phase II trial.

8016 Background: Thymic malignancies represent a therapeutic challenge in the advanced, metastatic setting, with limited options after the failure of platinum-based chemotherapy. Methods: NIVOTHYM is a multicenter phase II, 2-cohort, single-arm trial evaluating the use of nivolumab (N)+/-ipilimumab (I) in patients ≥18yo, with advanced/relapsed type B3 thymoma or thymic carcinoma (TC), after previous exposure to platinum-based chemotherapy.Primary endpoint wasProgression-Free Survival (PFS) rate at 6 months based on RECIST1.1 per independent radiological review. We report the results of cohort 2 with patients who received N 240 mg Q2W and I 1mg/kg Q6W. Results: From Feb 2021 to Jan 2023, 56 patients – 8 (14%) with type B3 thymoma, 48 (86%) with TC - were enrolled in 15 centers/5 countries, of which 37 (66%) men/19 (34%) women. Median age was 64 years. 23 (41%) patients had had surgery. After a median follow-up of 16.0 months, 50 patients had discontinued N+I for: progression in 36 (72%) pts, treatment-related adverse events (TRAEs) in 11 (22%) pts, completion in 2 (4%) pts, and pt decision for 1 pt (2%). Maximal grade of adverse events was 1/2 in 29 (52%) patients, and 3/4 in 27 (48%) patients. Grade ≥3 TRAEs occurred in 16 (29%) pts: myocarditis (2 pts), colitis (4 pts), infusion-related reaction/allergy (2 pts), skin rash (2 pts), heart failure, immune-related hepatitis, arthritis, myositis, hypophysitis, Gougerot Sjogren syndrome, pharyngitis, fatigue, fever, infusion-related reaction (1 pt each); there was no grade 5 TRAE. PFS rate at 6 months was 21.6%. Objective Response and Disease Control Rates were 17.7% and 60.8%, respectively. Median PFS and Overall Survival were 3.2 (95%CI 2.1-3.6) and 22.0 (95%CI 16.6-NR) months, respectively; median duration of response was 7.1 (95%CI 1.4-17.0) months, and 8 (14%) pts received treatment for ≥12 months. Conclusions: N+I demonstrated limited efficacy in advanced thymic tumors, as prespecified PFS rate at 6 months of 40% was not reached, compared to the previously reported cohort 1 of this trial with N as single-agent. Numerically more patients experienced grade ≥3 TRAEs, while efficacy endpoints were not numerically higher. Clinical trial information: NCT03134118 .