Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
RP2 · 4 trials · 5 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.
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. |
| 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 | 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 |
| Nivolumab | BIOLOGICAL | Nivolumab: Anti-PD-1 Monoclonal 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...