Administration of the PD-L1 inhibitor camrelizumab combined with the selective multikinase inhibitor famitinib elicited responses and was well tolerated in patients with advanced acral or mucosal melanoma previously exposed to an immune checkpoint inhibitor (ICI) regimen, according to data from a phase 2 trial (NCT05051865)presented at the 2023 ASCO Annual Meeting.

Of the 17 efficacy evaluable patients with prior ICI exposure, the overall response rate (ORR) with the regimen was 17.6%; this consisted of 2 patients with a confirmed partial response (PR) and 1 patient with an unconfirmed PR. Eight patients (47.1%) had stable disease (SD) and 6 patients (35.3%) experienced progressive disease (PD). The best percentage change in target lesion size from baseline was approximately 50% in 1 patient with acral melanoma. The disease control rate (DCR) was 64.7% in this population.

Moreover, at a median follow-up of 7.3 months, patients had an estimated median progression-free survival (PFS) of 6 months (95% CI, 2.6-9.5). The median overall survival (OS) was not yet reached.

In their presentation of the data, lead study author Lili Mao, MD, and colleagues, added that, “[The] safety profile [of the regimen] was consistent with [what has been observed in] prior studies of this combination, and no new safety signals were identified.” Mao is a researcher in the Key Laboratory of Carcinogenesis and Translational Research and in the Department of Melanoma and Sarcoma at Peking University Cancer Hospital and Institute in Beijing, China.

Acral and mucosal melanomas are characterized by an aggressive phenotype; accordingly, patients with these subtypes have a substantial need for effective yet tolerable therapeutic options, according to the investigators.

Prior research has established the efficacy of camrelizumab in combination with other antiangiogenic therapies in a previously untreated population of patients with melanoma. Moreover, famitinib has demonstrated benefit when paired with camrelizumab in several other tumor types due to its ability to produce both angiogenic and antiproliferative effects.

The single-arm, open-label prospective trial enrolled patients with unresectable stage III/IV acral and mucosal melanoma with an ECOG performance status between 0 and 1 and an expected survival of 12 weeks or longer. Patients were enrolled into 2 cohorts: those who had not received prior ICI treatment (cohort 1), and those who had (cohort 2).

All participants received 200 mg of intravenous camrelizumab every 3 weeks in addition to 20 mg of oral famitinib once daily. Treatment continued until patients experienced disease progression or unacceptable toxicity.

The study’s primary end point was ORR according to RECIST v1.1 criteria. Key secondary efficacy end points included PFS, DCR, and OS. Safety was also evaluated and described using NCI-CTCAE v5.0 descriptive guidelines.

Results presented at the 2023 ASCO Annual Meeting were from an analysis of efficacy and safety in cohort 2, which comprised a total of 18 patients. Nine patients had mucosal disease and 9 had acral disease. All patients had stage IV melanoma at the time of study entry.

In the overall population, the median age was 58 years (range, 38-71) and half of patients were female. Regarding ECOG performance status, 11.1% had a status of 0 and 88.9% had a status of 1. Most patients (61.1%) had received 1 prior line of treatment, 22.2% had received 2 prior lines, and 16.7% were exposed to 3 or more lines. BRAF, C-KIT and NRAS mutations were observed in 11.1%, 16.7%, and 16.7% of patients, respectively.

Previous ICI regimens included PD-L1 monotherapy (27.8%), anti–4-1BB monotherapy (5.6%), and a PD-L1 combination regimen (66.7%). Combinations included anti–PD-L1 therapy plus LAG-3 or CTLA-4 inhibitors (38.9%), a PD-L1 inhibitor plus oncolytic virus (11.1%), a PD-L1 inhibitor and chemotherapy (5.6%), PD-L1 and C-KIT inhibitors (5.6%), or a PD-L1 inhibitor and an antiangiogenic agent (5.6%).

Five patients were still on treatment at the time of data cutoff, which was January 12, 2023.

Regarding safety, 88.9% of all 18 patients experienced treatment-related adverse effects (TRAEs). Most events were grade 1 or 2, and no patients experienced a TRAE above grade 3.

The most common all-grade TRAEs observed in this population were decreased white blood cell count (27.8%), proteinuria (27.8%), hypertension (22.2%), diarrhea (22.2%), increased blood bilirubin (22.2%), hypothyroidism (22.2%), y–gamma-glutamyl increase (16.7%), alanine transaminase increase (16.7%), stomatitis (16.7%), platelet count decrease (16.7%), neutrophil count decrease (11.1%), aspartate transaminase increase (11.1%), anemia (5.6%), renal impairment (5.6%), hypokalemia (5.6%), hyperuricemia (5.6%), dermatitis allergic (5.6%), and palmar-plantar erythrodysesthesia syndrome (5.6%).

The most common grade 3 TRAE was neutrophil count decrease (11.1%), followed by white blood cell count decrease (5.6%), anemia (5.6%), renal impairment (5.6%) and hypokalemia (5.6%).

Editor’s Note: Dr Mao reported receiving institutional research funding from MSD. She also received honoraria from MSD, Novartis, and Shanghai Junshi Biosciences.