Efficacy and safety of RP1 combined with nivolumab in patients with anti–PD-1–failed melanoma from the IGNYTE clinical trial.

9517 Background: Patients (pts) with melanoma who progress on anti–PD-1 therapy (anti–PD-1–failed) have limited treatment options. RP1 is an HSV-1–based oncolytic immunotherapy expressing human GM-CSF and a fusogenic protein (GALV-GP-R−). Here, we present data from pts with anti–PD-1–failed melanoma, including the initial cohort and updated data from a registration-directed (R-D) cohort, from the phase 1/2 IGNYTE study (NCT03767348). Methods: Pts had locally advanced or metastatic cutaneous melanoma with ≥1 measurable and injectable tumor (≥1 cm) and confirmed progressive disease (PD) while on therapy and received anti–PD-1 ± anti–CTLA-4 therapy for ≥8 consecutive weeks, with anti–PD-1 being the last treatment received. Pts on prior adjuvant anti–PD-1 therapy had confirmed PD while on adjuvant therapy. RP1 was initially given intratumorally at 1×10 6 plaque-forming units (PFU)/mL and then every 2 weeks (Q2W) at 1×10 7 PFU/mL for up to 8 total cycles (≤10 mL/cycle) combined with nivolumab (nivo; cycles 2–8, 240 mg IV); pts then received nivo alone (240 mg Q2W or 480 mg Q4W IV) for up to 2 years, with the option to receive additional courses of RP1 if specified criteria were met. Results: Overall, 156 pts were enrolled (initial melanoma cohort, n = 16; R-D cohort, n = 140); 46.2% of pts had been treated with prior anti–PD-1 combined with anti–CTLA-4, and 51.3% of patients had stage IVM1b-d disease. The overall objective response rate (ORR) was 31.4%, and 12.2% of pts achieved complete response (CR; Table). Responses were observed irrespective of prior anti–PD-1 therapy setting and disease stage (Table). Responses were seen in uninjected lesions and in bulky and visceral disease. The ORR for pts with primary anti–PD-1 resistance was 34.1%. In pts who failed prior ipilimumab + nivo, the ORR was 26.4% (Table). The median duration of response (time from baseline to end of response for responders) was > 24 months, with 100% of responses lasting > 6 months from baseline; 78% of responses were ongoing. Treatment-related adverse events (TRAEs) associated with RP1 + nivo were predominantly grade 1–2; there was 1 grade 5 TRAE (immune-mediated myocarditis attributed to nivo). Conclusions: The updated data from this expanded cohort show that RP1 + nivo provides durable and clinically meaningful antitumor activity in pts with anti–PD-1–failed melanoma. Responses were observed in both injected and uninjected lesions, including visceral lesions. The combination continues to be well tolerated. Clinical trial information: NCT03767348 . [Table: see text]