KEY TAKEAWAYS
- The phase II trial aimed to investigate the efficacy of nivo/ipi plus cabozantinib in advanced melanoma pts.
- The primary endpoint was to determine the PFS. Secondary endpoints include ORR, OS, and AEs.
- The study found that Nivo/Ipi plus Cabo showed clinical activity in advanced melanoma but was insufficient to move to the next testing stage.
Nivolumab/Ipilimumab (Nivo/Ipi) is a standard advanced melanoma treatment with a 58% response rate and 49% progression-free survival(PFS) at 12 months. Cabozantinib(Cabo), a drug that targets c-MET/VEGFR2, has modest activity in melanoma and may boost anti-tumor immunity. Nivo/Ipi plus Cabo showed clinical activity and acceptable toxicity in genitourinary malignancies.
Researchers aimed to investigate the efficacy of Nivo/Ipi plus Cabo in advanced melanoma patients(pts).
The study administered induction treatment with Nivo 3mg/kg IV, Ipi 1mg/kg IV, and Cabo 40mg PO daily every 3 weeks for 4 cycles. This was followed by Nivo 480mg IV plus Cabo 40mg PO daily every 4 weeks for up to 2 years until disease progression or unacceptable toxicity/patient withdrawal. The study included pts with unresectable stage III/IV melanoma who had not been previously exposed to anti-PD-1 or CTLA-4 treatment, except in the adjuvant setting more than 6 months since their last dose. Uveal melanoma cases were excluded. The primary endpoint was the 12-month PFS rate, with secondary endpoints including objective response rate (ORR), overall survival (OS), and assessment of adverse events (AEs). After evaluating the first 14 subjects using a Simon 2-stage design, an interim analysis was planned to achieve more than 8 subjects with a 12-month PFS endpoint.
The study was conducted across three cancer centers within the Georgetown-Lombardi Comprehensive Cancer Center Consortium; 14 pts were enrolled. The median age was 66.5 years; all had stage IV disease, 10 with cutaneous primary site, 5 with elevated LDH, and 6 with BRAF V600 mutant tumor. The median follow-up was 10.6 mos. The primary endpoint of the 12-month PFS rate was 30% (3/10 evaluable subjects); 3 subjects pending PFS evaluation; median PFS 10.3 mos. ORR was 46% (6/13 evaluable subjects) with 2 CR, 4 PR, and 1 SD. Responders had cutaneous (5) or unknown (1) primary sites. 9 pts were alive at the last follow-up. The secondary endpoint of the 12-month OS rate was 67% (6/9 evaluable subjects). Reasons for treatment discontinuation included AEs (4), patient withdrawal (1), and disease progression (6). About 3 pts remain on the study drug(s). Treatment-related AEs (TRAEs) were observed in 13 subjects; 9 experienced a grade 3-4 TRAE (most frequent were elevated AST/ALT 29% and hypokalemia 14%). The most frequent grade 2 TRAEs were diarrhea (35%) and palmar-planter-erythrodysesthesia (29%). No treatment-related deaths occurred.
The study found that Nivo/Ipi plus Cabo showed clinical activity in advanced melanoma but was insufficient to move to the next testing stage. Side effects were similar to what has been seen before. Biomarker analyses are planned to find which pts benefit most from this treatment.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.9563
Clinical Trial: https://www.clinicaltrials.gov/study/NCT04091750
Geoffrey Thomas Gibney, Andrew L Pecora, Suthee Rapisuwon, Kevin Chen, Kellie Gardner, Gayle Cramer, Danielle Blair, Amy Avergas, Nicole Swanson, Jaeil Ahn, and Michael B. Atkins. DOI: 10.1200/JCO.2023.41.16_suppl.9563 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 9563-9563.
