In a Spanish-French phase II trial (SPOTLIGHT-203) reported in the Journal of Clinical Oncology, Márquez-Rodas et al investigated the combination of the intratumoral agent BO-112 and pembrolizumab for activity in patients with advanced anti–PD-1–resistant melanoma. BO-112 is a synthetic, double-stranded RNA nanoplexed with polyethylenimine that has shown potential in reversing such resistance in solid tumors.
Study Details
In the multicenter trial, 42 patients enrolled between January and August 2021 received intratumoral BO-112 (maximum dose per session = 2 mg, up to eight lesions per treatment) once weekly for the first 7 weeks and then every 3 weeks in combination with pembrolizumab at 200 mg every 3 weeks until progression or unacceptable toxicity or for up to 1 year. The primary outcome measure was objective response rate on independent central radiology review, with an efficacy threshold of 20%.
Key Findings
Among 40 evaluable patients, the objective response rate was 25%, with complete response in 10% and partial response in 15%; an additional 40% of patients had stable disease. At a median follow-up of 15.5 months, median duration of response was not reached (95% confidence interval [CI] = 8.3 months to not reached); responses were maintained at 9 and 12 months in 85.7% of responders.
Among all 42 patients, with a median follow-up of 15.5 months, median progression-free survival was 3.7 months (95% CI = 2.2–9.2 months), with rates at 6 and 12 months of 44.4% and 32.3%. With a follow-up of up to 24 months, median overall survival was not reached (95% CI = 9.9 months to not reached), with rates at 6, 12, and 24 months of 78.3%, 63.6%, and 53.7%.
The most common adverse events of any grade were asthenia (61.9%), pyrexia (45.2%), and diarrhea (30.9%). Grade ≥ 3 adverse events occurred in 38.1% of patients and were considered related to treatment in four patients (9.5%). Adverse events led to the discontinuation of any study treatment in 16.7% of patients. No treatment-related deaths were observed.
The investigators concluded: “The clinical trial has met its primary end point [objective response rate] making BO-112 with pembrolizumab a potential strategy to revert anti–PD-1 resistance in patients with [melanoma]. [Progression-free survival] results are in line with other clinical trials in anti–PD-1–resistant [scenarios], with promising [overall survival] data.”
Iván Márquez-Rodas, MD, PhD, of Hospital General Universitario Gregorio Marañon, Madrid, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Highlight Therapeutics S.L., in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. For full disclosures of all study authors, visit ascopubs.org.
