Study of RP3 Monotherapy and RP3 in Combination With Nivolumab in Patients With Solid Tumors
- Registration Number
- 2024-512710-17-00
- Lead Sponsor
- Replimune Group Inc.
- Brief Summary
RP2-001-18 is a Phase 1, multicenter, open label, single agent dose escalation and combination treatment study of RP2 in adult subjects with advanced solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.
- Detailed Description
RP2 is a genetically modified herpes simplex type 1 virus (HSV-1) that expresses an anti-CTLA-4 antibody and is designed to directly destroy tumors and to generate an anti-tumor immune response. This is a Phase 1, multicenter, open label, dose escalation and expansion, first-in-human (FIH) clinical study to evaluate the safety and tolerability, biodistribution, shedding, and preliminary efficacy of RP2 alone and in combination with nivolumab in adult subjects with advanced solid tumors.
The study will be conducted in two parts. The first part of the study is an open-label, dose escalation FIH Phase 1 study to assess the safety and tolerability of RP2 and to determine the recommended Phase 2 dose (RP2D) to be used in the second part of the study. The second part of the study is an open label design to further investigate safety of RP2 in combination with nivolumab. It will also assess the biological activity of multiple doses of RP2 in combination with nivolumab. An expansion to the second part of the study will include enrolment of a further 30 patients on RP2 in combination with nivolumab.
Following completion of the expansion in part 2, part 3 will enroll a further 15 patients on RP3 monotherapy.
The expansion to part 2 and part 3 will focus on patients with advanced or metastatic uveal melanoma, lung cancer, breast cancer or GI cancers and patients with liver metastasis.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Not specified
- Target Recruitment
- 36
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose escalation of RP2 - superficial tumors RP2 Dose escalation of RP2 alone in 3 cohorts with IT injections in superficial tumors. Dose escalation of RP2 - deep/visceral tumors RP2 Dose escalation of RP2 alone in 3 cohorts with imaging guided IT injections in deep/visceral tumors. Dose expansion of RP2 and nivolumab - superficial tumors RP2 Doses of RP2 (IT) in superficial tumors with nivolumab (IV). Dose expansion of RP2 and nivolumab - superficial tumors nivolumab Doses of RP2 (IT) in superficial tumors with nivolumab (IV). Dose expansion of RP2 and nivolumab - deep/visceral tumors RP2 Imaging guided doses of RP2 (IT) in deep/visceral tumors. Dose expansion of RP2 and nivolumab - deep/visceral tumors nivolumab Imaging guided doses of RP2 (IT) in deep/visceral tumors. Seronegative cohort RP2 Doses of RP2 (IT) in HSV seronegative participants.
- Primary Outcome Measures
Name Time Method Percentage of dose limiting toxicities (DLTs) From Day 1 up to 30 days after last dose. Percentage of subjects with DLTs
Percentage of TEAEs ≥ Grade 3 From Day 1 up to 60 days after last dose. Percentage of subjects with TEAEs ≥ Grade 3
Maximum tolerated dose (MTD) of RP2 7 months MTD on the safety and response data collected during the dose escalation phase (Part 1).
Percentage of adverse events (AEs) From Day 1 up to 60 days after last dose Percentage of subjects with AEs
Percentage of serious adverse events (SAEs) From Day 1 up to 60 days after last dose Percentage of subjects with SAEs
Recommended Phase 2 dose (RP2D) of RP2 7 months RP2D of RP2 based on the safety and response data collected during the dose escalation phase (Part 1).
Percentage of treatment emergent adverse events (TEAEs) From Day 1 up to 60 days after last dose. Percentage of subjects with TEAEs
Percentage of events requiring withdrawal From Day 1 up to last dose (up to 8 weeks for dose escalation phase and up to 2 years for expansion phase)). Percentage of subjects experiencing events requiring withdrawal from treatment.
- Secondary Outcome Measures
Name Time Method Percentage of biologic activity 20 weeks Percentage of subjects with biological activity determined by tumor biopsies and biomarker data
Change in HSV-1 antibody levels From Day 1 up to last dose (up to 4 months for dose escalation phase and up to 5.5 months for expansion phase)). Change in HSV-1 antibody levels during treatment compared to baseline
Median duration of response 3 years Median duration of response of subjects
Percentage of complete response (CR) From Day 1 up to last dose (up to 8 weeks for escalation phase and up to 2 years for expansion phase). Percentage of subjects with a CR
Percentage of stable disease (SD) From Day 1 up to last dose (up to 8 weeks for escalation phase and up to 2 years for expansion phase). Percentage of subjects with SD
Median progression-free survival 3 years Median duration of progression-free survival of subjects
Percentage of subjects with detectable RP2 20 weeks Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of RP2.
Percentage of overall response rate (ORR) 3 years Percentage of ORR.
Median overall survival 3 years Median overall survival rate of subjects
Percentage of partial response (PR) From Day 1 up to last dose (up to 8 weeks for escalation phase and up to 2 years for expansion phase). Percentage of subjects with a PR
Trial Locations
- Locations (7)
Hospital Universitario d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
Hospital Clinico de Valencia
🇪🇸Valencia, Spain
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Bebington, Merseyside, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧London, United Kingdom
Churchill Hospital
🇬🇧Oxford, United Kingdom
Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
Hospital Universitario d'Hebron🇪🇸Barcelona, Spain