P-58 An ongoing open-label, phase 2 trial of RP2 Or RP3 oncolytic immunotherapy in combination with atezolizumab and bevacizumab for the treatment of patients with advanced colorectal carcinoma

Colorectal cancer (CRC) is the third most frequently diagnosed and second leading cause of cancer-related mortality worldwide. PD-1/PD-L1 inhibition, in combination with other modalities, has demonstrated clinical benefit patients microsatellite instability-high or mismatch repair–deficient CRC, but little no stable (MSS) repair–proficient (pMMR) CRC. RP2 an enhanced potency oncolytic herpes simplex virus type 1 that expresses fusogenic gibbon ape leukemia glycoprotein R sequence deleted (GALV-GP-R–), human granulocyte-macrophage colony-stimulating factor (GM-CSF), anti–CTLA-4 antibody-like molecule; RP3 additionally 4-1BB CD40 activating ligands does not express GM-CSF. Preliminary data from phase studies have promising safety efficacy either agent solid tumors. This open-label, nonrandomized, 2 study will evaluate atezolizumab bevacizumab advanced MSS pMMR CRC (NCT05733611). Patients a histologic diagnosis unresectable and/or metastatic documented status, previously treated up to 3 standard-of-care systemic regimens be enrolled + treatment groups (30 per group). Further key inclusion criteria include having at least measurable injectable tumor (≥1 cm), Eastern Cooperative Oncology Group performance status 0–1, adequate hepatic, renal, hematologic function. RP2/RP3 injected into tumors by direct (including via colonoscope) image-guided injection. receive 8 total doses 10 mL RP2/RP3, first dose concentration × 6 plaque-forming units (PFU)/mL, followed 7 PFU/mL every weeks, then 4 weeks. may course injections without if protocol-specified are met. Bevacizumab administered starting on day (with RP2/RP3); week (fourth RP2/RP3) within 72 hours administration RP2/RP3. The primary endpoint objective response rate; secondary endpoints safety, overall survival, progression-free duration response, benefit, complete rate. Exploratory assessment health-related quality life, changes biomarkers, biodistribution/shedding Antitumor activity evaluated using Response Evaluation Criteria Solid Tumors version 1.1 as modified for this study. undergo radiologic evaluation screening weeks until confirmed disease progression; assessments also conducted whenever clinically significant progressive suspected. Safety assessed physical examination, laboratory evaluations, vital signs, monitoring adverse events (AEs; including serious AEs). AE severity according National Cancer Institute Common Terminology Adverse Events, 5.0. NCT05733611. Medical writing editorial support were provided Marita Chakhtoura, PhD, AlphaBioCom, LLC, Red Nucleus Company (King Prussia, PA, USA) funded Replimune Inc. (Woburn, MA, USA).