Study of RP1 Monotherapy and RP1 in Combination With Nivolumab
- Conditions
- Non-melanoma Skin CancerMicrosatellite InstabilityCancerMismatch Repair DeficiencyCutaneous MelanomaNSCLCMelanoma (Skin)
- Interventions
- Registration Number
- NCT03767348
- Lead Sponsor
- Replimune Inc.
- Brief Summary
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 340
- 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) who has progressed on prior anti-PD1/PD-L1 therapy.
- 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). Patients must have received 8 weeks of anti-PD1/PD-L1 as their last line of therapy and progressed while on treatment.
- 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: must have failed prior treatment, including PD1/PD-L1 directed therapy administered either as monotherapy or in combination with platinum-based chemotherapy or anti-CTLA-4. The most recent treatment given must have included an anti-PD1/PD-L1 directed therapy with radiologic disease progression on or after treatment.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors RP1 Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV) Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors RP1 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 nivolumab Doses of RP1 (IT) in superficial tumors with nivolumab (IV) RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC RP1 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 NMSC RP1 Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer Dose escalation of RP1 by intratumoral (IT) injection in superficial tumors RP1 Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors RP1 Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with MSI-H or dMMR solid tumors Dose expansion of RP1 and nivolumab (IV) in superficial tumors RP1 Doses of RP1 (IT) in superficial tumors with nivolumab (IV) RP1 (IT) and nivolumab (IV) in melanoma RP1 Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma RP1 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 NSCLC RP1 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 RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC nivolumab 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 RP1 (IT) and nivolumab (IV) in melanoma nivolumab Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors nivolumab Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV) RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma nivolumab 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 MSI-H/dMMR solid tumors nivolumab 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 nivolumab 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/PD-L1 Failed NMSC nivolumab 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
- Primary Outcome Measures
Name Time Method Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1 20 weeks Assess the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1 based on the safety and response data collected during Phase 1 Escalation
Percentage of adverse events (AEs) 26 months Percentage of subjects with adverse events (AEs)
Percentage of serious adverse events (SAEs) 26 months Percentage of subjects with serious adverse events (SAEs)
Percentage of overall response rate (ORR) 26 months Percentage of overall response rate (ORR) for all participants
Percentage of dose limiting toxicities (DLTs) 26 months Percentage of subjects with dose limiting toxicities (DLTs)
- Secondary Outcome Measures
Name Time Method Percentage of complete response (CR) 26 months Percentage of subjects with a complete response (CR)
Median overall survival 26 months Median overall survival rate of subjects
Percentage subjects with detectable RP1 20 weeks Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of RP1
Median progression-free survival 26 months Median duration of progression-free survival of subjects
Percentage of biologic activity 20 weeks Percentage of subjects with biological activity determined by tumor biopsies and biomarker data
Median duration of response 26 months Median duration of response of subjects
Trial Locations
- Locations (52)
University of Birmingham Alabama
🇺🇸Birmingham, Alabama, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Carti Cancer Center
🇺🇸Little Rock, Arkansas, United States
UC San Diego
🇺🇸La Jolla, California, United States
University of Southern California
🇺🇸Los Angeles, California, United States
UCLA
🇺🇸Los Angeles, California, United States
University of California, Irvine
🇺🇸Orange, California, United States
University of California- San Francisco
🇺🇸San Francisco, California, United States
Sylvester Comprehensive Cancer Center- University of Miami
🇺🇸Miami, Florida, United States
Scroll for more (42 remaining)University of Birmingham Alabama🇺🇸Birmingham, Alabama, United States