Title
Study of RP1 Monotherapy and RP1 in Combination With Nivolumab
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
Phase
Phase 1/Phase 2Lead Sponsor
Replimune Inc.Study Type
InterventionalStatus
RecruitingStudy Participants
340RPL-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.
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.
Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors
Dose escalation of RP1 alone in 3 cohorts with IT injections in deep/visceral tumors
Doses of RP1 (IT) in superficial tumors with nivolumab (IV)
Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with MSI-H or dMMR solid tumors
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer
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
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
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) 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. 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
