Description:
RPL-001-16 is a Phase 1/2, open label, dose escalation and expansion clinical study of RP1
alone and in combination with nivolumab in adult subjects with advanced and/or refractory
solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose
(RP2D), as well as to evaluate preliminary efficacy.
Title
- Brief Title: Study of RP1 Monotherapy and RP1 in Combination With Nivolumab
- Official Title: An Open-Label, Multicenter, Phase 1/2 Study of RP1 as a Single Agent and in Combination With PD1 Blockade in Patients With Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
RPL-001-16
- NCT ID:
NCT03767348
Conditions
- Cancer
- Melanoma (Skin)
- Mismatch Repair Deficiency
- Microsatellite Instability
- Non-melanoma Skin Cancer
- Cutaneous Melanoma
- NSCLC
Interventions
| Drug | Synonyms | Arms |
|---|
| RP1 | | Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors |
| nivolumab | Opdivo | Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors |
Purpose
RPL-001-16 is a Phase 1/2, open label, dose escalation and expansion clinical study of RP1
alone and in combination with nivolumab in adult subjects with advanced and/or refractory
solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose
(RP2D), as well as to evaluate preliminary efficacy.
Detailed Description
RP1 is a genetically modified herpes simplex type 1 virus that is designed to directly
destroy tumors and to generate an anti-tumor immune response. This is a Phase 1/2, open
label, multicenter, dose escalation and expansion, first-in-human (FIH) clinical study to
evaluate the safety and tolerability, biodistribution, shedding, and preliminary efficacy of
RP1 alone and in combination with nivolumab in adult subjects with advanced and/or refractory
solid tumors. The study will include a dose escalation phase for single agent RP1, an
expansion phase with a combination of RP1 and nivolumab and a Phase 2 portion in specified
tumor types for the combination therapy.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Dose escalation of RP1 by intratumoral (IT) injection in superficial tumors | Experimental | Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors | |
| Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors | Experimental | Dose escalation of RP1 alone in 3 cohorts with IT injections in deep/visceral tumors | |
| Dose expansion of RP1 and nivolumab (IV) in superficial tumors | Experimental | Doses of RP1 (IT) in superficial tumors with nivolumab (IV) | |
| Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors | Experimental | Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV) | |
| RP1 (IT) and nivolumab (IV) in melanoma | Experimental | Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma | |
| RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors | Experimental | Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with MSI-H or dMMR solid tumors | |
| RP1 (IT) and nivolumab (IV) in NMSC | Experimental | Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer | |
| RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma | Experimental | Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with cutaneous melanoma who have been previously treated with anti-PD1 therapy | |
| RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC | Experimental | Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer who have been previously treated with anti-PD1/PD-L1 therapy | |
| RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC | Experimental | Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non small cell lung cancer who have been previously treated with anti-PD1/PD-L1 therapy | |
Eligibility Criteria
Inclusion Criteria:
- Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
- At least one measurable and injectable lesion
- Have provided a former tumor pathology specimen or be willing to supply a new tumor
sample from a biopsy
- Have a predicted life expectancy of ≥ 3 months
- Measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST)
v1.1 criteria
- Subjects with MSI-H or dMMR tumors: has diagnosis of MSI-H or metatstatic dMMR tumor
(according to protocol definition) for whom anti PD-1 therapy is indicated, or have
refused, become intolerant to or have no further therapy options available
- Subjects with NMSC: has diagnosis of locally advanced or metastatic NMSC that are not
considered treatable by surgery including basal cell carcinoma, cutaneous squamous
cell carcinoma, basosquamous carcinoma, Merkel cell carcinoma and other non-melanoma
skin cancers (per protocol) for whom anti-PD1/PD-L1 therapy is indicated, or have
refused, become intolerant to or have no further therapy options available
- Subjects with anti-PD1 failed cutaneous melanoma: has confirmed progressive disease
while on anti-PD1 treatment for at least 8 weeks and documented BRAF mutation status
- Subjects with anti-PD1 failed NSCLC: has confirmed progressive disease after no more
than two prior systemic treatments including anti-PD1/PD-L1 treatment
Exclusion Criteria:
- Prior treatment with an oncolytic therapy
- History of viral infections according to the protocol
- Prior complications with herpes infections
- Chronic use of anti-virals
- Uncontrolled/untreated brain metastasis
- History of interstitial lung disease
- History of non-infectious pneumonitis
- History of clinically significant cardiovascular disease
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Percentage of adverse events (AEs) |
| Time Frame: | 26 months |
| Safety Issue: | |
| Description: | Percentage of subjects with adverse events (AEs) |
Secondary Outcome Measures
| Measure: | Percentage of biologic activity |
| Time Frame: | 20 weeks |
| Safety Issue: | |
| Description: | Percentage of subjects with biological activity determined by tumor biopsies and biomarker data |
| Measure: | Percentage subjects with detectable RP1 |
| Time Frame: | 20 weeks |
| Safety Issue: | |
| Description: | Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of RP1 |
| Measure: | Percentage of complete response (CR) |
| Time Frame: | 26 months |
| Safety Issue: | |
| Description: | Percentage of subjects with a complete response (CR) |
| Measure: | Median duration of response |
| Time Frame: | 26 months |
| Safety Issue: | |
| Description: | Median duration of response of subjects |
| Measure: | Median progression-free survival |
| Time Frame: | 26 months |
| Safety Issue: | |
| Description: | Median duration of progression-free survival of subjects |
| Measure: | Median overall survival |
| Time Frame: | 26 months |
| Safety Issue: | |
| Description: | Median overall survival rate of subjects |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Replimune Inc. |
Trial Keywords
- Oncolytic virus
- Oncolytic Immuno-gene therapy
- Non-melanoma Skin Cancer
- Cutaneous Melanoma
- Anti-PD1 failed
- Melanoma (skin)
Last Updated
July 29, 2021
