Avelumab with axitinib in persistent or recurrent cervical cancer after platinum-based chemotherapy (ALARICE study).

5540 Background: Platinum-based chemotherapy with or without bevacizumab and pembrolizumab is the standard treatment option for advanced or recurrent cervical cancer. However, immunotherapy is only approved for PD-L1 positive tumors. This study aimed to evaluate the efficacy and tolerability of avelumab and axitinib in persistent or recurrent cervical cancer irrespective of PD-L1 status. Methods: This is a phase 2, single-arm, Simon’s 2-stage, pilot study. Eligible patients with cervical cancer after at least one line of platinum-based chemotherapy, not previously exposed to immunotherapy, received avelumab (10 mg/kg) every two weeks and axitinib 5 mg BD at 4-weekly cycle for 12 cycles unless there was disease progression or intolerable side effects. The primary objective was to determine the objective response rate (ORR). Results: 21 patients were enrolled in the study during Jun 2019 to May 2022. The median age was 57 (range 37-78). 11 patients (52.4%) had squamous cell carcinoma, and 15/17 (88.2%) had PD-L1 combined positive score >1. The median number of lines of chemotherapy was 1 (range 1-2), and the median number of cycles of avelumab received was 9 (range 2–12). The study ended prematurely because the pre-specified endpoint was reached in the first stage. The ORR assessed by an independent radiologist was 33.3% (7/21) and disease-control rate was 52.4% (11/21) in the intention-to-treat group, and 38.9% and 61.1%, respectively, in the per-protocol group where three patients did not have follow-up scans. 4 patients had complete response, and 2 remained disease-free even without any treatment after completion of the study drugs. The median duration of response of the whole cohort was 14.3 months (range 11.0-32.2 months). 4 of the responders were platinum-resistant. The median progression-free survival from the first day of avelumab was 10.7 months (95% CI 3-18.5) and overall survival was 20.9 months (95% CI 6.6-35.2). Two pre-specified safety reviews were performed after recruiting the 5 th and the 10 th patients, and there were excessive serious adverse events that were concerning. All patients experienced adverse events, and the most common included grade 1-2 skin rash (52.4%) and proteinuria (42.9%). 16 patients (76.2%) required to reduce the dosage of axitinib, and the final dose was 2 mg in 8 patients. Using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), EORTC QLQ – Cervical cancer 24 (QLQ-CX24) and EuroQoL EQ-5D-5L questionnaires, no deterioration of patients’ reported outcomes were observed over the study period. Further biomarker analyses are being performed. Conclusions: Avelumab and axitinib could produce a durable and clinically meaningful response in cervical cancer irrespective. These results supported further evaluation of this combination in recurrent or even primary cervical cancer. Clinical trial information: NCT03826589 .