RP2 demonstrated promising response rates and tolerability in the treatment of metastatic uveal melanoma, both as a monotherapy and in combination with nivolumab.
New data from a cohort of a phase 1 study (NCT04336241) of RP2, an engineered herpes simplex virus, as a single agent and in combination with nivolumab (Opdivo) show that the treatment is tolerable and potentially efficacious in patients with metastatic uveal melanoma, according to Replimune, RP2’s manufacturer.1
Joseph Sacco, MBChB, PhD, FRCP, University of Liverpool and Clatterbridge Cancer Centre, presented the data at a plenary session at the 20th International Congress of the Society for Melanoma Research in Philadelphia, Pennsylvania, held November 6-9.
Out of 17 evaluable patients, treatment with RP2 demonstrated an overall response rate (ORR) of 29.4% (n = 5). Four patients were treated with RP2 and nivolumab, and 1 patient received RP2 monotherapy. Responses were observed in patients with liver, lung, and bone metastases. The median duration of response (DOR) was 11.47 months (range, 2.78-21.22+). Fifteen of 17 patients had progressed on or after immunotherapy treatment; 12 of 17 patients had received both anti-PD1 and anti-CTLA-4 therapy, including 4 of the responding patients.
For safety, the most common grade 1 or 2 treated-related adverse events (TRAEs) across both cohorts were pyrexia, chills, fatigue, hypotension, and pruritus. There were 6 patients who experienced grade 3 TRAEs, which included 2 cases of hypotension. No grade 4 or 5 TRAEs were observed.
“Metastatic uveal melanoma is an immunologically cold tumor type with few effective treatment options,” Sacco said in his presentation. “The data from this study are compelling given the rate of durable responses seen combined with a favorable safety profile, including in patients who had both liver and extra-hepatic metastases, further supporting the potential of RP2 in this patient population.”
The phase 1, multicenter, open-label, dose-escalation, and combination study of RP2 in patients with advanced solid tumors aims to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) and investigate preliminary efficacy. The study has an estimated enrollment of 36 patients and an estimated completion date of April 2028.2
The primary end points are the percentages of adverse events (AEs), serious AEs, dose-limiting toxicities, TRAEs, TRAEs grade 3 or higher, and AEs requiring study withdrawal. MTD and RP2D are also primary end points. Secondary end points include percentage of biologic activity, subjects with detectable RP2, change in HSV-1 antibody levels, ORR, median DOR, median progression-free survival, median overall survival, rate of complete responses, rate of partial responses, and rate of stable disease.
To be eligible, patients must have advanced or metastatic non-neurological tumors and have progressed on or are intolerant to standard therapy, as well as an ECOG performance status of 0-1. Patients are not eligible to participate if they have received prior treatment with an oncolytic virus, have a history of chronic antiviral use, have received systemic cancer therapy within 5 half-lives or 4 weeks of first study dose, or have a history of myocarditis or congestive heart failure.
“These data from the trial cohort evaluating RP2 as monotherapy and in combination with nivolumab in metastatic uveal melanoma are highly promising,” said Robert Coffin, president and chief research and development officer at Replimune, in a press release.1 “We are currently assessing the potential registrational path forward for RP2 in advanced uveal melanoma now that the phase 1 development of RP2 in this disease is nearly complete.”
Findings from a recent phase 1 data support the further investigation of SD-101, a class C toll-like receptor-9 agonist, in the treatment of patients with metastatic uveal melanoma with liver metastases.