New molecular entity
Development and Regulatory status
Phase I Clinical Trials
An oncolytic immunotherapy that encodes for CD40 ligand (CD40L) and 4-1BB ligand (4-1BBL) in addition to the GALV-GP R(-) fusogenic protein encoded in RP 1 and the anti-CTLA-4 molecule encoded in RP 2 also being developed by Replimune.
Variable depending on tumour type.
Trial or other data
Mar 22Replimune reports that as monotherapy, they have dosed three patients in the PI study (NCT04735978) at a low dose and three at a high dose in a variety of hard-to-treat salvage therapy patients with injections of RP3 into both superficial and deep tumours, including injections into the lung and liver. The higher dose level has been confirmed as the recommended Phase 2 dose (RP2D). A seventh patient has also recently been enrolled such that three HSV seronegative patients in total have been treated at the RP2D. The first six patients enrolled in this Phase 1 clinical trial had heavily pre-treated advanced sarcoma, esophageal cancer, colorectal cancer, head and neck cancer and melanoma. Three of the six patients (with melanoma and colorectal cancer) died due to disease progression approximately two to four months from initiating the study, indicating the advanced nature of disease of the patients enrolled. Two other patients also had rapid progressive disease, and one patient with esophageal cancer had stable disease out to one year. Thus, while no new safety signals having been observed as compared to RP1 or RP2, based on the patients enrolled it is too early to draw any conclusions as to efficacy. Enrollment into the cohort of patients dosed with RP3 combined with Opdivo has also recently commenced. This cohort will focus on enrolling patients with GI cancers, breast cancer, lung cancer and head and neck cancer. Initial data for the combination cohort is expected towards the end of the year. Additional patients will also be dosed as monotherapy .
Dec 20PI study of RP 3 both alone and in combination with anti-PD-1 therapy in patients with advanced solid tumours starts (NCT04735978). This open-label, dose-escalation and expansion, sequential, multicentre clinical trial intends to enroll 123 adults in the UK (at The Clatterbridge Cancer Centre, The Royal Marsden Hospital and the Churchill Hospital in Oxford). In Part 1 - Dose Escalation - participants will be enrolled into two sequential dose level cohorts. Cohort 1: 1 × 105 plaque-forming units (PFU)/mL on Day 1 followed by 1 × 106 PFU/mL every 2 weeks (Q2W) for up to 5 doses. Cohort 2: 1 × 106 PFU/mL on Day 1 followed by 1 × 107 PFU/mL Q2W for up to 5 doses. In Part 2 - Dose Combination - patients will be enrolled into 1 of 5 dose-expansion cohorts. Expansion Cohorts 1, 2, and 4 will enroll patients with head and neck cancer, lung cancer, breast cancer, or GI cancer. Expansion Cohort 3 will enroll patients with any solid organ malignancy who have at least 2 tumors that can be injected and biopsied. Expansion Cohort 5 will enroll patients with melanoma. Expansion Cohort 1 (RP3 + Nivolumab); Expansion Cohort 2 (RP3 Followed by Nivolumab); Expansion Cohort 3 (RP3 Monotherapy Translational Cohort); Expansion Cohort 4 (RP3 Monotherapy); Expansion Cohort 5 (RP3 + Nivolumab in Melanoma). Collection of primary outcome data is due to complete Apr 24 .