Novel Immunotherapy Combination After Anti–PD-1 Therapy Fails in Advanced Melanoma

By: Jenna Carter, PhD
Posted: Monday, August 12, 2024

In a study presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 9517), researchers discussed the use of RP1—a modified herpes simplex virus—based oncolytic immunotherapy expressing human GM-CSF and a fusogenic protein—and the PD-1 inhibitor nivolumab in patients whose melanoma did not respond to anti–PD-1 therapy. Michael K.K. Wong, MD, PhD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues reported an overall objective response rate of 34.1% and a complete response rate of 12.2% with this novel combination in patients who have primary anti–PD-1 resistance.

A total of 156 patients with locally advanced or metastatic cutaneous melanoma were enrolled in the phase I/II IGNYTE study. Patients also had confirmed progressive disease while on therapy and received anti–PD-1 with or without anti–CTLA-4 therapy for 8 or more consecutive weeks, with anti–PD-1 being the last treatment received. Enrolled patients who had prior adjuvant anti–PD-1 therapy had confirmed progressive disease while on adjuvant therapy. Patients initially received RP1 intratumorally at 1 × 10⁶ plaque-forming units (PFU)/mL and then every 2 weeks at 1 × 10⁷ PFU/mL for up to eight total cycles (≤ 10 mL/cycle) combined with nivolumab (cycles 2–8, 240 mg IV). They then received nivolumab alone (240 mg every 2 weeks or 480 mg every 4 weeks IV) for up to 2 years, with the option to receive additional courses of RP1 if specified criteria were met.

Responses were observed regardless of whether patients had received anti–PD-1 therapy and the disease stage, including in uninjected lesions and in bulky and visceral disease. The objective response rate for patients with primary anti–PD-1 resistance was 34.1%, and it was 26.4% in patients who failed to respond to prior treatment with ipilimumab plus nivolumab. The median duration of response was at least 24 months, with 100% of responses lasting more than 6 months. Treatment-related adverse events associated with RP1 plus nivolumab were found to be predominantly grade 1 to 2.

Disclosure: For full disclosures of the study authors, visit coi.asco.org.

2024 ASCO Annual Meeting

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