Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as RP2 (vusolimogene oderparepvec), RP2 Injection, RP2 Monotherapy
RP2 · 5 trials · 6 indications
The best overall response is the best response recorded from the start of the treatment until disease progression (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Responses do not require confirmation. Complete response (CR) is complete disappearance of all target lesions. Partial response (PR) is at least 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Determine the rate of major pathologic response (MPR) following neoadjuvant combination therapy with RP2 and nivolumab in patients with resectable stage IIIB-IV cutaneous melanoma.
OS is the time from the date of randomization to death from any cause.
PFS is the time from randomization to first evidence of confirmed disease progression as assessed by BICR per RECIST 1.1 or death from any cause.
The proportion of patients achieving a BOR of CR or PR per RECIST 1.1 among those that are evaluable for response.
Percentage of subjects with AEs
Percentage of subjects with SAEs
Percentage of subjects with DLTs
Percentage of subjects with TEAEs
Percentage of subjects with TEAEs ≥ Grade 3
Percentage of subjects experiencing events requiring withdrawal from treatment.
MTD on the safety and response data collected during the dose escalation phase (Part 1).
RP2D of RP2 based on the safety and response data collected during the dose escalation phase (Part 1).
| Arm | Type | Description |
|---|---|---|
| RP2 Injection | EXPERIMENTAL | Enrolled participants will complete the following: * A 3 subject safety run-in will be conducted with participants enrollment staggered. If \> 1 subject experiences a grade 4-5 adverse event (AE), study enrollment will pause for review by PI and study sponsor. If there are 0 grade 4-5 AEs, enrollment will proceed. * Baseline in-clinic visit with assessments, oral mucosal punch biopsy, and RP2 injection (week 1). * In-clinic visits on weeks 3, 5, 7, 8, 9, 11, 13, 15, and 16. * RP2 injections on weeks 1, 3, 5, 7, 9, 11, 13, and 15. * Repeat oral mucosal punch biopsy at week 8. * Follow up: every 3 months for up to 2 years. |
| RP2 + Nivolumab | EXPERIMENTAL | RP2 + Nivolumab Followed by Surgery and Adjuvant Nivolumab |
| Test Arm: RP2 + nivolumab | EXPERIMENTAL | RP2 (Oncolytic virus) and Nivolumab (programmed death receptor-1 (PD-1) inhibitor) |
| Control Arm (Active Comparator): ipilimumab + nivolumab | EXPERIMENTAL | Immune Checkpoint inhibitor combination |
| RP2+Bevacizumab and Atezolizumab | EXPERIMENTAL | HCC Cohort 1a and 1b: Patients with locally advanced unresectable, recurrent and/or metastatic HCC who have progressed on 1 prior systemic treatment, which must have included anti-programmed cell death 1 (PD-1)/anti-PD-L1 therapy. Patients will receive atezolizumab plus bevacizumab therapy combined with RP2. In cohort 1a, patients will receive RP2 intratumorally every 2 weeks (Q2W) for 4 doses, then every 3 weeks (Q3W) for 4 doses combined with atezolizumab plus bevacizumab. In cohort 1b, patients will receive RP2 intratumorally every 2 weeks (Q2W) for 8 doses combined with atezolizumab plus bevacizumab. |
| RP2 Monotherapy | EXPERIMENTAL | HCC Cohort 2: Patients with locally advanced unresectable, recurrent and/or metastatic HCC who have progressed on 1 prior systemic treatment, which must have included anti-programmed cell death 1 (PD-1)/anti-PD-L1 therapy. Patients will receive RP2 monotherapy every 2 weeks (Q2W). |
| RP2+Durvalumab | EXPERIMENTAL | BTC Cohort (Cohort 3): Patients with locally advanced or metastatic BTC (intrahepatic or extrahepatic cholangiocarcinoma or gall bladder carcinoma), who have received treatment with combination gemcitabine, platinum-containing chemotherapy, and checkpoint inhibitor for a minimum of 12 weeks (4 to 8 cycles) and maximum of 24 weeks, and who have had stable disease or partial response on 2 on treatment scans and no progressive disease. After the last combination chemotherapy treatment, checkpoint inhibitor treatment must be limited to 2 doses (8 weeks). Patients will receive durvalumab combined with RP2. |
| Dose escalation of RP2 - superficial tumors | EXPERIMENTAL | Dose escalation of RP2 alone in 3 cohorts with IT injections in superficial tumors. |
| Dose escalation of RP2 - deep/visceral tumors | EXPERIMENTAL | 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 | EXPERIMENTAL | Doses of RP2 (IT) in superficial tumors with nivolumab (IV). |
| Dose expansion of RP2 and nivolumab - deep/visceral tumors | EXPERIMENTAL | Imaging guided doses of RP2 (IT) in deep/visceral tumors. |
| Seronegative cohort | EXPERIMENTAL | Doses of RP2 (IT) in HSV seronegative participants. |
| Name | Type | Description |
|---|---|---|
| RP2 Injection | BIOLOGICAL | Genetically modified live HSV-1 virus, 3.0 mL single-use glass vials, via intralesional (into a lesion) injection per protocol. |
| RP2 (vusolimogene oderparepvec) | DRUG | RP2 (vusolimogene oderparepvec) RP2 will be injected directly into the tumor every 2 weeks for three doses before surgery. |
| Nivolumab | DRUG | Nivolumab will be administered by intravenous infusion at a dose of 240 mg every 2 weeks for 3 doses during the neoadjuvant period, followed by 480 mg every 4 weeks for 11 doses during the adjuvant period. |
| Definitive Surgical Resection | PROCEDURE | Participants will undergo definitive surgical resection of all clinically resectable melanoma lesions following completion of neoadjuvant treatment with RP2 and nivolumab. Surgery will be performed according to standard clinical practice and institutional guidelines. Resected tumor tissue and, where applicable, involved lymph nodes will be collected and evaluated for pathologic response and other study-related assessments. |
| RP2 | BIOLOGICAL | Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation. |
| Ipilimumab | BIOLOGICAL | Ipilimumab: human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody |
| Bevacizumab | BIOLOGICAL | Anti-VEGF therapy. |
| Atezolizumab | BIOLOGICAL | Anti-PD-L1 monoclonal antibody. |
| Durvalumab | BIOLOGICAL | Anti-PD-L1 monoclonal antibody |
| RP2 Monotherapy | BIOLOGICAL | Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation. |
Inclusion Criteria: * Patients with a diagnosis of high-risk OPD defined by any of the following: * Proliferative leukoplakia (PL) * Localized leukoplakia showing at least moderate dysplasia not treated with surgery * Erythroplakia (regardless of dysplasia) * High-risk LOH profile: 9p21 or...
RP2 is an investigational cancer therapy being developed by Replimune Group, Inc. (ticker: REPL). It is being studied across several oncology indications, including metastatic uveal melanoma, hepatocellular carcinoma, high-risk oral precancerous disease, and resectable cutaneous melanoma. RP2 is not yet approved and remains in clinical development.
RP2 is being studied in metastatic uveal melanoma as a combination treatment with nivolumab in immune checkpoint inhibitor-naive adults. This is evaluated in the Phase 2/3 trial NCT06581406, which is currently recruiting participants across the United States, Australia, and the United Kingdom. RP2 is investigational and has not been approved for this or any indication.
RP2 targets CTLA-4, an immune checkpoint protein. By binding CTLA-4, RP2 is designed to act on a pathway that regulates T-cell immune responses. It is being developed as an oncology therapy and is currently in clinical development.
RP2 is developed by Replimune Group, Inc., which trades under the ticker REPL. The company is the sponsor of the clinical trials evaluating RP2 across its oncology indications.
RP2 is in Phase 1 development overall, with additional Phase 2 and Phase 2/3 studies ongoing. It is investigational and has not been approved by the FDA. Trials include NCT07862530, NCT06623110, NCT06581406, and NCT05733598, which cover melanoma, oral precancerous disease, uveal melanoma, and hepatocellular carcinoma.
RP2 is being evaluated in several trials. NCT06581406 is a Phase 2/3 study in metastatic uveal melanoma, NCT05733598 is a Phase 2 study in hepatocellular carcinoma, NCT06623110 is a Phase 2 immunoprevention study in high-risk oral precancerous disease, and NCT07862530 is a Phase 2 neoadjuvant study in melanoma.
Yes, RP2 is also known as vusolimogene oderparepvec and RP2 Injection. These names refer to the same investigational oncology therapy developed by Replimune Group, Inc. (ticker: REPL).