A Phase II trial presented at the 2023 ASCO Annual Meeting showed that combining the PD-L1 inhibitor camrelizumab with the selective multikinase inhibitor famitinib yielded positive responses and was well-tolerated in patients with advanced acral or mucosal melanoma who had previously received immune checkpoint inhibitor (ICI) treatment.
Out of the 17 patients evaluated for efficacy who had prior ICI exposure, the overall response rate (ORR) with this regimen was 17.6%. This included 2 patients with confirmed partial response (PR) and 1 patient with unconfirmed PR. Additionally, 47.1% of patients had stable disease (SD), while 35.3% experienced progressive disease (PD). Notably, one patient with acral melanoma displayed a significant reduction of approximately 50% in target lesion size. The disease control rate (DCR) in this group was 64.7%.
After a median follow-up of 7.3 months, the estimated median progression-free survival (PFS) was 6 months (95% CI, 2.6-9.5). The median overall survival (OS) had not yet been reached.
Lead author Lili Mao, MD, and colleagues emphasized that the safety profile of the regimen aligned with previous studies of the combination, with no new safety concerns identified. Mao, a researcher at Peking University Cancer Hospital and Institute in Beijing, China, noted the urgent need for effective and well-tolerated treatment options for patients with aggressive acral or mucosal melanoma.
Previous studies have demonstrated the effectiveness of camrelizumab in combination with other antiangiogenic therapies for treatment-naïve melanoma patients. Famitinib has also shown benefits when paired with camrelizumab in various tumor types, thanks to its ability to produce angiogenic and antiproliferative effects.
The trial was a single-arm, open-label study that enrolled patients with unresectable stage III/IV acral or mucosal melanoma and an ECOG performance status between 0 and 1. Patients were divided into two 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 and 20 mg of oral famitinib once daily. Treatment continued until disease progression or unacceptable toxicity occurred.
The analysis presented at the 2023 ASCO Annual Meeting focused on efficacy and safety in cohort 2, which consisted of 18 patients with advanced melanoma. The primary endpoint of the study was objective response rate (ORR) assessed by RECIST v1.1 criteria. Key secondary efficacy endpoints included progression-free survival (PFS), disease control rate (DCR), and overall survival (OS). Safety was evaluated using NCI-CTCAE v5.0 descriptive guidelines.
Among the patients in the overall population, the median age was 58 years (range: 38-71) and half of them were female. The Eastern Cooperative Oncology Group (ECOG) performance status was 0 for 11.1% of the patients and 1 for 88.9% of them. At the time of study entry, all patients had stage IV melanoma. Mucosal disease was observed in 9 patients, while 9 had acral disease.
In terms of prior treatment, most patients (61.1%) had received one prior line of treatment, 22.2% had received two prior lines, and 16.7% had been exposed to three or more lines. BRAF, C-KIT, and NRAS mutations were observed in 11.1%, 16.7%, and 16.7% of patients, respectively.
Previous immune checkpoint inhibitor (ICI) regimens included PD-L1 monotherapy (27.8%), anti-4-1BB monotherapy (5.6%), and a PD-L1 combination regimen (66.7%). Combination therapies consisted of 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 plus chemotherapy (5.6%), PD-L1 and C-KIT inhibitors (5.6%), or a PD-L1 inhibitor plus an antiangiogenic agent (5.6%).
As of the data cutoff on January 12, 2023, five patients were still undergoing treatment.
In terms of safety, 88.9% of all 18 patients experienced treatment-related adverse effects (TRAEs). Most TRAEs were grade 1 or 2, and no patients experienced a TRAE higher than grade 3.
The most common TRAEs of any grade observed in this patient 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%), gamma-glutamyl transferase 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%), allergic dermatitis (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%).
