An open-label, multicenter, phase 1 study of RP3 as a single agent and in combination with nivolumab in patients (pts) with solid tumors.

Abstract

TPS2705 Background: RP3 is a genetically modified herpes simplex virus 1 (HSV-1) that contains insertions for the gibbon ape leukemia virus surface glycoprotein (GALV-GP) with the R- sequence deleted (R-), an anti–cytotoxic T lymphocyte antigen 4 (CTLA-4) antibody-like molecule, CD40 ligand, and 4-1BB ligand. Together, these insertions are expected to increase oncolytic potency, cell-to-cell spread, immunogenic cell death, and systemic immune activation. RP3 has demonstrated antitumor activity in preclinical models using viruses similar to RP3 expressing murine versions of anti-CTLA-4, CD40L, and 4-1BBL both alone and in combination with PD1-1 blockade. Methods: This is an open-label, multicenter, Phase 1 study evaluating RP3 as monotherapy or in combination with nivolumab (nivo) in patients (pts) with solid tumors (NCT04735978). Part 1 evaluated escalating doses of RP3. Pts in Part 1 received IT injections of up to 10 mL RP3 into superficial, nodal, or visceral lesions Q2W x 5 across two dose levels (DL1: 105 plaque-forming units (PFU)/mL once, then 106 PFU/mL x 4; DL2: 106 PFU/mL once, then 107 PFU/mL x4). The RP2D is 106 PFU/mL once, followed by 107 PFU/mL IT Q2W. In Part 2, pts are being enrolled into expansion cohorts of 45 patients with GI (including HCC), lung, breast, and squamous cell carcinoma of the head and neck treated with RP1 combined with nivo. Additional cohorts will enroll patients treated with RP3 followed by nivo, RP3 monotherapy to further explore biomarkers in injected and uninjected tumors, and with the potential to also open a cohort in melanoma. Pts in both Part 1 and Part 2 may receive up to 8 additional doses of RP3 if protocol-specified criteria are met. Key inclusion criteria: confirmed advanced or metastatic non-neurological solid tumors, at least one measurable tumor ≥ 1 cm and injectable tumors ≥ 1 cm in aggregate, ECOG ≤1, and adequate hematologic, hepatic, and renal function. In Cohorts 1, 2, and 4, approximately 50% of the pts with lung, breast, and GI cancer must have liver lesions intended for injection. Exclusion criteria include prior oncolytic virus treatment, need for immunosuppressive therapy, an autoimmune disease requiring systemic therapy, active significant herpetic infections or prior complications of HSV-1 infection, active or chronic HBV or HCV infection, known HIV infection, or prior active malignancy within 3 years. Clinical trial information: NCT04735978.