IGNYTE: A Phase 1/2 Multi-Cohort Clinical Trial of RP1 ± Nivolumab in Patients with Non-Small Cell Lung Cancer and Other Solid Tumors

Abstract

<h3>Purpose/Objective(s)</h3> RP1 is an enhanced potency oncolytic HSV-1 which expresses a fusogenic glycoprotein (GALV-GP R-) and granulocyte macrophage colony stimulating factor (GM-CSF). In pre-clinical studies, RP1 demonstrated a potent GALV-GP R-enhanced anti-tumor activity and immunogenic cell death and initial clinical data in a range of tumor types has been promising, including in patients with anti-PD1 failed disease. The Phase 1 part of the study demonstrated a tolerable safety profile for RP1 and RP1 combined with nivolumab (nivo) and determined the recommended phase 2 dose (RP2D). The objective of the Phase 2 part of the study is to evaluate the safety and efficacy of RP1 combined with nivo in patients (pts) with a range of advanced solid tumors, including anti-PD-1/PD-L1-failed non-small-cell lung cancer (NSCLC). <h3>Materials/Methods</h3> The Phase 2 portion of this multi-center, open label clinical trial is enrolling approximately 270 pts across five cohorts, including 30 pts in an anti-PD-1/PD-L1-failed NSCLC cohort, as well as patients with anti-PD1 failed and naïve melanoma, non-melanoma skin cancers and MSI-H/dMMR tumors. Pts in the Ph 2 portion receive up to 10 mL of RP1 intratumorally into one or more superficial or deep seated/visceral lesions by imaging guidance at the RP2D identified in the Phase 1 portion of the study (1 × 10⁶ PFU/mL × 1 followed by 1 × 10⁷ PFU/mL × 7, Q2W). Following the first dose of RP1, nivo (240 mg IV Q2W for 4 months then 480 mg IV Q4W for up to 2 years) is subsequently administered in combination. Pts may receive up to 8 additional doses of RP1 if they meet protocol-specified criteria. Tumor assessments are performed Q8W. The primary objectives of the Ph 2 part of the study are to assess the safety, tolerability, and overall response rate (ORR) of RP1 in combination with nivo. Secondary objectives include duration of response, complete response rate, disease control rate, PFS, 1-year and 2-year survival rates. Exploratory objectives include biodistribution and shedding analysis of RP1 and biomarker studies, including analyses of tumor biopsies and blood samples. Enrollment is currently ongoing in the US, UK and EU. <h3>Results</h3> TBD/NA (Trial-in-Progress) <h3>Conclusion</h3> TBD/NA (Trial-in-Progress)