New Data With RP1 Plus Nivolumab in PD-1–Refractory Melanoma Build on Positive Findings

The oncolytic immunotherapy RP1 in combination with nivolumab (Opdivo) displayed activity in patients with melanoma who failed prior anti–PD-1 treatment, according to updated findings from the phase 2 IGNYTE trial (NCT03767348).¹

Per independent central review, patients who received the combination (n = 140) achieved an objective response rate (ORR) of 33.6% by modified RECIST v1.1 criteria and 32.9% per RECIST v1.1. Moreover, the responses were durable; 100% of responses lasted more than 6 months and the median duration of response (DOR) was over 35 months.²

“The overall strength of the IGNYTE data and safety profile further highlights the potential of RP1 in a difficult treatment setting with limited options for patients,” Sushil Patel, PhD, the chief executive officer of Replimune, said in a press release.¹ “Based on these compelling results and recent FDA interactions, we are increasingly confident in our path forward. We have shared the results with the agency and plan to request a pre-BLA meeting, in advance of our intended BLA submission. With these data in hand, we are preparing for a commercial launch next year.”

RP1 is made up of a proprietary engineered strain of herpes simplex virus, the fusogenic protein GALV-GP R- and GM-CSF. The agent is designed to maximize tumor killing potency, enhance the immunogenicity of tumor cell death, and activate the systemic anti-tumor response of the immune system.

IGNYTE enrolled patients with advanced melanoma who experienced disease progression during previous anti–PD-1 therapy with at least 1 measurable lesion who did not receive a prior oncolytic therapy and had an ECOG performance status of 1 or less. Anti–PD-1 failure was defined as receiving the agent for at least 8 weeks and experiencing confirmed disease progression; the anti–PD-1 treatment was required to be the last therapy prior to entering IGNYTE.³

In the anti–PD-1-failed cutaneous melanoma cohort, patients received the first dose of RP1 28 days after screening, followed by RP1 plus nivolumab 240 mg for cycles 2 through 8. Then, nivolumab monotherapy was given at the same dose for cycle 9 followed by nivolumab 480 mg every 4 weeks for cycles 10 through 30. The safety follow-up was 100 days and there was a 3-year follow-up from the last patient enrolled.

The coprimary end points were safety and ORR per modified RECIST v1.1 assessed by independent central review. Secondary end points included ORR by investigator assessment, DOR, progression-free survival, and overall survival.

The updated data added to investigator-assessed findings from IGNYTE that were presented during the 2024 ASCO Annual Meeting. Patients in the overall population (n = 156) experienced an ORR of 32.7%, including a complete response rate of 14.7%. The estimated median DOR was 36.57 months (95% CI, 23.89-not reached); the 6-, 12-, 18-, and 24-month DOR rates were 100%, 84.2%, 74.9%, and 65.2%, respectively.

In terms of safety, there were no grade 5 treatment-related adverse effects (TRAEs) and there was a low incidence of grade 3 and 4 effects. The most common any-grade TRAEs included chills (34.0%), fatigue (33.3%), pyrexia (31.4%), and nausea (22.4%). In the data update, Replimune noted that the combination continues to be well tolerated.^1,3

Replimune stated that RP1 is well positioned for a biologics license application (BLA) submission and commercialization. The first patient is expected to be enrolled to the confirmatory phase 3 IGNYTE-3 trial (NCT06264180) in the third quarter of 2024 and the company is planning to submit the BLA to the FDA in the second half of the year. IGNYTE-3 will compare RP1 plus nivolumab with physician’s choice of therapy in patients with advanced cutaneous melanoma who progressed of anti–PD-1 and anti–CTLA-4 therapies or those who are not suitable candidates for anti–CTLA-4 treatment.²

References

1. Replimune announces positive topline primary analysis data by independent central review from IGNYTE clinical trial of RP1 plus nivolumab in anti-PD1 failed melanoma. News release. Replimune Group, Inc. https://www.globenewswire.com/news-release/2024/06/06/2894545/0/en/Replimune-Announces-Positive-Topline-Primary-Analysis-Data-by-Independent-Central-Review-from-IGNYTE-Clinical-Trial-of-RP1-plus-Nivolumab-in-Anti-PD1-Failed-Melanoma.html
2. Primary analysis of the IGNYTE registrational cohort in anti-PD1 failed melanoma. Replimune Group, Inc. June 6, 2024. Accessed June 6, 2024. https://ir.replimune.com/static-files/2137036f-c2da-405c-b661-7f557bbdc781
3. Wong MKK, Sacco JJ, Robert C, et al. Efficacy and safety of RP1 combined with nivolumab in patients with anti–PD-1–failed melanoma from the IGNYTE clinical trial. J Clin Oncol. 2024;42(suppl 16):9517. doi:10.1200/JCO.2024.42.16_suppl.9517