Patients 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.
Researchers have reported preliminary results on safety and activity of Avelumab ( Bavencio ) combined with Axitinib ( Inlyta ) in this patients population.
The CAVEATT is a single arm, multicentric, phase II trial in immunotherapy-naive patients with advanced B3 thymoma or thymic carcinoma, progressing after at least one line of Platinum based chemotherapy.
Prior therapy with antiangiogenic drugs was allowed.
Patients 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 was overall response rate ( ORR ) by RECIST 1.1; secondary endpoints included ORR by irRC and ITMIG, and QoL by EORTC QLQ-C30.
An interim futility analysis was planned after the enrollment of the first 18 patients. If at least 5 out of 18 patients will obtain a partial response ( PR ), the accrual will continue to reach the total number of 33 patients, 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.
1 patient with B3 thymoma and 12 with thymic carcinoma were enrolled from April 2019 to January 2020. Median age was 59 years ( range 33-77 ).
8 patients received greater than or equal to 2 previous line of therapies, and 6 patients were pretreated with an antiangiogenic drug.
The median follow-up was 5.1 months.
10 patients were evaluable for response. The proportions of patients who achieved a partial response or a stable disease ( SD ) were respectively 40% ( 95% CI 17%–69% ) and 60% ( 95% CI 30%–83% ).
The median progression-free survival ( PFS ) was 7.9 months ( 95% CI 2.5–NA ) 12 patients were evaluable for toxicity.
Treatment-related adverse events of grade 1 or 2 occurred in 7 ( 58% ) patients, and the most common was diarrhea ( 3 patients ).
Grade greater than or equal to 3 adverse effects occurred in 2 ( 17% ) patients: 1 had G3 hyperthension and 1 G3 hand foot syndrome, both leading to Axitinib drug reduction.
No immune-related adverse effects ( irAEs ) were observed.
No patient stopped treatment for toxicity, 5 patients stopped for progressive disease, and 8 patients are still on treatment.
In conclusion, preliminary results have suggested promising antitumor activity and a good toxicity profile of the combination of Axitinib and Avelumab in patients with advanced B3 thymoma and thymic carcinoma.
Accrual is ongoing to reach the target of 33 patients. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020