Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial

Abstract

Purpose: Camrelizumab is an antibody against programmed death protein 1. We assessed the activity and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, in patients with advanced cervical cancer.

Methods: This multicenter, open-label, single-arm, phase II study enrolled patients with advanced cervical cancer who progressed after at least one line of systemic therapy. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once per day. The primary end point was objective response rate (ORR) assessed by investigators per RECIST version 1.1. Key secondary end points were progression-free survival (PFS), overall survival (OS), duration of response, and safety.

Results: Forty-five patients were enrolled and received treatment. Median age was 51.0 years (range, 33-67 years), and 57.8% of patients had previously received two or more lines of chemotherapy for recurrent or metastatic disease. Ten patients (22.2%) had received bevacizumab. Median follow-up was 11.3 months (range, 1.0-15.5 months). ORR was 55.6% (95% CI, 40.0% to 70.4%), with two complete and 23 partial responses. Median PFS was 8.8 months (95% CI, 5.6 months to not estimable). Median duration of response and median OS were not reached. Treatment-related grade 3 or 4 adverse events (AEs) occurred in 71.1% of patients, and the most common AEs were hypertension (24.4%), anemia (20.0%), and fatigue (15.6%). The most common potential immune-related AEs included grade 1-2 hypothyroidism (22.2%) and reactive cutaneous capillary endothelial proliferation (8.9%).

Conclusion: Camrelizumab plus apatinib had promising antitumor activity and manageable toxicities in patients with advanced cervical cancer. Larger randomized controlled trials are warranted to validate our findings.

Trial registration: ClinicalTrials.gov NCT03816553.

Figures

FIG 1.

Trial profile.

FIG 2.

Antitumor activity. The patients in the efficacy evaluable population are included (n = 41). (A) Best percentage change from baseline in target lesion. The dashed line at –30% change represents the RECIST version 1.1 cutoff to define partial response or complete response. (B) Duration of responses. The length of each bar represents the duration treatment of each patient. HPV, human papillomavirus; PD-L1, programmed death-ligand 1.

FIG 3.

Kaplan-Meier curves of duration of response, progression-free survival, and overall survival. (A) Duration of response was assessed in responders (n = 25), and (B) progression-free survival and (C) overall survival were assessed in the intention-to-treat population (n = 45). NE, not estimable; NR, not reached.

FIG 4.

Kaplan-Meier estimates of progression-free survival by programmed death-ligand 1 (PD-L1) expression. Progression-free survival was assessed in patients with available PD-L1 expression (n = 40). We compared curves from the PD-L1–positive and the PD-L1–negative population using the log-rank test. NE, not estimable; NR, not reached.