Camrelizumab Plus Apatinib and Temozolomide as First-Line Treatment in Patients With Advanced Acral Melanoma: The CAP 03 Phase 2 Nonrandomized Clinical Trial

Abstract

Importance: Acral melanoma, known for low tumor mutation burden, responds poorly to immunotherapy. A standard therapy is still lacking.

Objective: To investigate the activity and safety of camrelizumab (an anti-programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor 2 inhibitor) and temozolomide as first-line treatment in patients with advanced acral melanoma.

Design, setting, and participants: In this single-arm, single-center, phase 2 nonrandomized clinical trial, patients with treatment-naive unresectable stage III or IV acral melanoma were enrolled at Peking University Cancer Hospital and Institute between June 4, 2020, and August 24, 2021. The data cutoff date was April 10, 2022.

Interventions: Patients received 4-week cycles of intravenous camrelizumab, 200 mg, every 2 weeks; oral apatinib 250 mg, once daily; and intravenous temozolomide, 200 mg/m2, once daily on days 1 to 5 until disease progression or unacceptable toxic effects.

Main outcomes and measures: The primary end point was objective response rate as assessed by investigators according to the Response Evaluation Criteria In Solid Tumors (version 1.1). Secondary end points included progression-free survival, time to response, duration of response, disease control rate, overall survival, and safety.

Results: A total of 50 patients (32 men [64%]; median age, 57 years [IQR, 52-62 years]) were enrolled and received treatment. The median follow-up duration was 13.4 months (IQR, 9.6-16.2 months). The objective response rate was 64.0% (32 of 50; 95% CI, 49.2%-77.1%). The median time to response and duration of response were 2.7 months (IQR, 0.9-2.9 months) and 17.5 months (95% CI, 12.0 to not reached), respectively. The disease control rate was 88.0% (44 of 50; 95% CI, 75.7%-95.5%). The estimated median progression-free survival was 18.4 months (95% CI, 10.6 to not reached). The median overall survival was not reached. The most common grade 3 or 4 treatment-related adverse events were increased gamma-glutamyltransferase levels (15 [30%]), decreased neutrophil count (11 [22%]), increased conjugated bilirubin levels (10 [20%]), and increased aspartate aminotransferase levels (10 [20%]). No treatment-related deaths occurred.

Conclusions and relevance: The findings of this nonrandomized clinical trial suggest that camrelizumab plus apatinib and temozolomide may be a potential first-line treatment option for patients with advanced acral melanoma, which warrants further validation in a randomized clinical trial.

Trial registration: ClinicalTrials.gov Identifier: NCT04397770.

Figure 1.. Patient Flowchart

Two patients discontinued treatment (1 death and 1 patient decision) before the first postbaseline imaging examination; thus, they were excluded from the efficacy-evaluable set.

Figure 2.. Objective Response Rate in Different Subgroups of the Full Analysis Set

CPS indicates combined positive score; ECOG, Eastern Cooperative Oncology Group; LDH, lactic dehydrogenase; PD-L1, programmed cell death-ligand 1; PS, performance status; ULN, upper limit of normal (240 U/L).

Figure 3.. Waterfall Plot and Swimmer Plot Among Individual Patients in the Full Analysis Set

A, A lymph node was identified as the only target lesion in the patient with complete response, which regressed to normal length (from 22 mm to 9 mm) and met the definition of complete response according to the Response Evaluation Criteria In Solid Tumors, version 1.1. Two patients discontinued treatment before the first postbaseline imaging examination; thus, the change in their target lesions could not be shown in panel A. The horizontal lines represent 20% tumor growth and 30% tumor shrinkage. ^aLactic dehydrogenase (LDH) less than or equal to upper limit of normal (ULN). ^bProgrammed cell death ligand 1 (PD-L1) combined positive score (CPS) of 5 or greater.

Figure 4.. Kaplan-Meier Curves for Progression-Free Survival and Overall Survival in the Full Analysis Set