The combination of camrelizumab, apatinib, and temozolomide demonstrated activity in patients with acral melanoma (AM), according to phase 2 results presented at the ASCO Annual Meeting 2022.1
In previous studies, apatinib plus temozolomide produced an overall response rate (ORR) of 17.2% in patients with advanced melanoma, and camrelizumab plus apatinib produced an ORR of 22.2% in advanced AM.2,3
The aim of the current study was to evaluate whether the combination of all 3 agents could result in better responses.
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The phase 2 study (ClinicalTrials.gov Identifier: NCT04397770) enrolled 50 adults with unresectable stage III or metastatic AM who had received no prior systemic treatment in the advanced setting.
At baseline, the median age was 57 years (range, 24-73), 64% of patients were men, 96% had stage IV disease, and 62% had wild-type NRAS.
Patients received camrelizumab at 200 mg every 2 weeks, apatinib at 250 mg daily, and temozolomide at 200 mg/m2 on days 1-5 of each 28-day cycle. Patients were treated until disease progression, intolerable toxicity, or the 2-year mark.
The median duration of treatment was 9.2 months, and the median follow-up was 14.0 months.
The primary endpoint was ORR, and 48 patients were evaluable for response. The ORR was 66.7%. One patient achieved a complete response, 31 had a partial response, and 12 had stable disease. The disease control rate was 91.7%.
The median time to response was 2.7 months, and the median duration of response was 17.5 months.
The median progression-free survival (PFS) was 18.4 months, and the median overall survival (OS) was not reached. The 12-month PFS rate was 65.1%, and the 12-month OS rate was 91.6%.
Treatment-related adverse events (TRAEs) occurred in 96% of patients. Grade 3 TRAEs occurred in 50%, and grade 4 TRAEs occurred in 12%. There were no fatal TRAEs.
The most common grade 4 TRAEs were hypokalemia (4%), gamma-glutamyltransferase elevation (4%), thrombocytopenia (4%), conjugated bilirubin elevation (2%), and neutropenia (2%).
Treatment discontinuation of any study drug was required in 1 patient, 36% required dose interruptions, and 26% required dose reductions.
Disclosures: This study was sponsored by Beijing Cancer Hospital. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
References
1. Lu S, Li C, Bai X, et al. A phase II clinical trial of camrelizumab (CAM, an IgG4 antibody against PD-1) combined with apatinib (APA; a VEGFR-2 tyrosine kinase inhibitor) and temozolomide (TMZ) as first-line treatment for patients (pts) with advanced acral melanoma (AM). Presented at ASCO 2022; June 3-7, 2022. Abstract 9508.
2. Zhou L, Yang Y, Si L, et al. Phase II study of apatinib combined with temozolomide in patients with advanced melanoma after failure of immunotherapy. Melanoma Res. 2022;32(3):142-149. doi:10.1097/CMR.0000000000000809
3. Wang X, Cui C, Lian B, et al. Apatinib in combination with camrelizumab, a humanized immunoglobulin G4 monoclonal antibody against programmed cell death-1, in patients with metastatic acral melanoma. J Clin Oncol. 2021;39:15_suppl, 9539-9539. doi:10.1200/JCO.2021.39.15_suppl.9539
