Replimune Group, Inc. has announced the enrollment of the first patients in two clinical trials evaluating RP2, a novel oncolytic immunotherapy, for the treatment of metastatic uveal melanoma and hepatocellular carcinoma (HCC). These trials mark a significant step in expanding the potential of Replimune's RPx platform.
RP2-202 Trial in Metastatic Uveal Melanoma
The RP2-202 trial (NCT06581406) is a randomized, phase 2/3 study designed to enroll approximately 280 immune checkpoint inhibitor-naïve adult patients with metastatic uveal melanoma. Uveal melanoma, a cancer originating in the tissues of the eye, has a high propensity for metastasis, with the liver being the most common site in 90-95% of cases. The trial will evaluate RP2 in combination with nivolumab versus ipilimumab in combination with nivolumab. The primary endpoints are overall survival and progression-free survival, with key secondary endpoints including overall response rate and disease control rate.
Dr. Justin Moser, an associate clinical investigator at HonorHealth Research Institute, emphasized the importance of this trial for uveal melanoma patients, stating, "We are honored and excited to be able to offer this clinical trial to our patients with uveal melanoma, a group of patients for whom treatment options are very limited. We hope that, by providing our patients with early access to treatments through clinical trials, that we will be able to help give them longer, higher-quality lives."
Previously presented data from a Phase 2 study at ASCO 2024 showed that RP2, either alone or combined with nivolumab, demonstrated an overall response rate of 29.4% and a disease control rate of 58.8% in uveal melanoma patients (n=17).
RP2-003 Trial in Hepatocellular Carcinoma
The RP2-003 trial (NCT05733598) is an open-label study that will enroll 30 patients with locally advanced unresectable, recurrent, and/or metastatic HCC. HCC is a leading cause of cancer-related deaths globally, representing 75-85% of primary liver cancer cases. Patients in the trial will receive RP2 in combination with atezolizumab and bevacizumab, a second-line therapy regimen. The primary endpoint of the study is overall response rate (ORR) per modified RECIST 1.1 criteria, with key secondary endpoints including ORR per RECIST modified for HCC and duration of response. This trial is being conducted under a collaboration and supply agreement with Roche.
About RP2
RP2 is derived from RP1, Replimune’s lead product candidate. RP1 is based on a proprietary strain of herpes simplex virus engineered with a fusogenic protein (GALV-GP R-) and GM-CSF to maximize tumor-killing potency, enhance the immunogenicity of tumor cell death, and activate a systemic anti-tumor immune response. RP2 further expresses an anti-CTLA-4 antibody-like molecule, along with GALV-GP-R- and GM-CSF. The goal of RP2 is to deliver these proteins directly to the sites of immune response initiation within the tumor and draining lymph nodes, thereby focusing systemic immune-based efficacy on tumors while limiting off-target toxicity.
Sushil Patel, Ph.D., CEO of Replimune, commented on the advancement of the RP2 program, stating, "On the heels of our BLA submission for RP1 and designation as breakthrough therapy, we are pleased that the first patients have been enrolled in both the RP2 HCC clinical trial and the registration intended study of RP2 in metastatic uveal melanoma. We are excited to explore the broader potential of the RPx platform and these RP2 clinical trials will play an important part of our future development plans."
