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Soo Park, MD
Soo Park, MD
Posted: Wednesday, June 26, 2024
According to Omid Hamid, MD, of The Angeles Clinic and Research Institute, Los Angeles, and colleagues, the novel PRAME (preferentially expressed antigen in melanoma) x CD3 ImmTAC (immune-mobilizing monoclonal T-cell receptor against cancer) bispecific protein brenetafusp (also known as IMC-F106C; PRAME-A02) was well tolerated both alone and in combination with anti–PD-1 therapy. Clinical activity was seen as monotherapy, in patients with immune checkpoint inhibitor–pretreated, HLA-A*02:01–positive unresectable or metastatic cutaneous melanoma. These findings from a phase I trial, which were presented during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 9507), support its evaluation in combination with nivolumab in the first-line setting in the phase III PRISM-MEL-301 trial.
Patients were administered two step-up doses and a weekly target dose of brenetafusp with (n = 6; target: 160 µg) or without (n = 40; target: 20–320 µg) 400 mg of pembrolizumab every 6 weeks. Follow-up data were provided for a median of 11 months. According to the investigators, adverse events were consistent with prior experience. Cytokine-release syndrome of grades 1 and 2 (50%) was the most common adverse event. The safety profile for the combination therapy appeared to be consistent with those of the individual agents.
Among the 31 patients who received monotherapy and were evaluable for tumor assessment, the clinical benefit rate (partial response or stable disease) was 61%. The clinical benefit rate was 65% in the 26 patients with PRAME-positive disease; it included all 35% of patients with any confirmed tumor reduction (42% of the PRAME-positive population). In the five PRAME-negative patients, no tumor reduction was reported. The PRAME-positive vs -negative population demonstrated a longer median progression-free survival (4.5 vs 2.1 months) and higher 6-month rate of overall survival (94% vs 40%). Of the 22 patients with PRAME-positive disease who had evaluable circulating tumor DNA, 41% had a molecular response.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
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