A combination of camrelizumab with apatinib and temozolomide has good antitumor activity as first-line therapy in patients with advanced acral melanoma, according to research presented at the 2022 ASCO Annual Meeting.
The single-center, single-arm, phase 2 study (ClinicalTrials.gov Identifier: NCT04397770) assessed efficacy and safety of the 3-drug combination in patients aged 18 to 75 years with unresectable stage III or metastatic acral melanoma who had not received any systemic antitumor therapy in the advanced setting. This treatment strategy combines immunotherapy (camrelizumab), inhibition of vascular endothelial growth factor receptor 2 signaling (apatinib), and induction of apoptosis (temozolomide).
All patients on the study received camrelizumab (200 mg every 2 weeks), apatinib (250 mg once per day), and temozolomide (200 mg/m2 on days 1-5), until disease progression or intolerable toxicity. A cycle was considered to be 28 days.
The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety.
Of the 50 patients enrolled (median age, 57 years; 64% male), 48 were evaluable. In all, 32 patients had a response (1 complete and 31 partial), translating to an ORR of 66.7% (95% CI, 51.6%-79.6%). The DCR was 91.7% (95% CI, 80.0%-97.7%).
Patients’ median time to response was 2.7 months (interquartile range, 0.9-3.2), and 11 of 48 patients (22.9%) had achieved a partial response by the first radiographic evaluation, after 2 cycles of treatment. The median duration of response was 17.5 months (95% CI, 12.0 to not reached) and the median treatment duration was 9.2 months (range, 0.9 to 21.6).
The cohort had a median follow-up of 14.0 months. The 6-month PFS rate was 84.8%, and the 12-month PFS rate was 65.1%, with an estimated median PFS duration of 18.4 months. The 12-month OS rate was 91.6%, and the median OS duration was not reached.
Subgroup analysis showed a trend whereby patients with a normal lactate dehydrogenase level at baseline had better OS vs those with an elevated level. Also, patients having partial response as their best response had better PFS and OS compared with those having stable disease.
The incidence of treatment-related adverse events (TRAEs) of any grade was 96% and of grade 3 or 4 was 62%. The most frequently occurring grade 4 TRAEs included hypokalemia (4.0%), γ-glutamyl transferase elevation (4.0%), thrombocytopenia (4.0%), conjugated bilirubin elevation (2.0%), and neutropenia (2.0%).
The median time to onset of grade 3 and 4 TRAEs was 4.1 months, and the median time to relief was 10 days. Most of the immune-related AEs were transient and manageable.
“A randomized controlled trial to verify the efficacy of this combination therapy as first-line treatment for patients with advanced acral melanoma is planned to be initiated,” the researchers commented.
Disclosure: This research was supported by Jiangsu Hengrui Pharmaceuticals Co, Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Si L, 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 the first-line treatment for patients (pts) with advanced acral melanoma (AM). Presented at ASCO 2022; June 3-7, 2022. Abstract 9508.