Safety and feasibility of intratumoral injection of RP1 or RP2 oncolytic immunotherapies in visceral metastases.

Abstract

2597 Background: RPx is an investigational HSV-1-based oncolytic immunotherapy platform including RP1 (vusolimogene oderparepvec) and RP2. RP1 expresses GM-CSF and a fusogenic glycoprotein (GALV-GP-R – ); RP2 also expresses an anti–CTLA-4 antibody-like molecule. We report safety data from patients (pts) who received intratumoral (IT) injections of RP1/2 into visceral metastases (mets). Methods: Pts with advanced/metastatic solid tumors were enrolled into RP1/2 clinical trials (RP1: NCT03767348; RP2: NCT04336241). RP1/2 was injected into visceral tumors using CT or ultrasound guidance. The recommended needle gauges ranged from 17-27G. Pts received RP1/RP2 for up to 8 doses as monotherapy or in combination with nivolumab IV starting at cycle 2 or 4 for up to 2 years. Additional RP1/2 doses could be given if protocol-specified criteria were met. This analysis evaluated safety among pts receiving IT RP1/2 injections to visceral mets (defined as lung or liver mets). All safety data presented includes events occurring within 7 days after injection (except where noted). Results: As of data cutoff (RP1: 15OCT2024; RP2: 29AUG2025), there were a total of 665 RP1/2 injections into the lung (n = 125; median lung injections/pt/treatment course [c]: RP1 = 5.5 and RP2 = 8) and liver (n = 540; median liver injections/pt/c): RP1 and RP2 = 5) among 105 pts. The most common treatment-related adverse events (AEs) were pyrexia, chills, and fatigue (Table). A total of 9 pneumothorax (PTX) events occurred (within 3 days after injection) out of 125 lung injections (7.2%) in 19 pts receiving RP1/2; all cases were Grade (G) 1/2 and resolved. Only 1 pt required a chest tube for a G2 PTX event and the pt continued to receive RP1 after resolution. There were 3 bleeding events within 3 days after injection among 665 injections (0.5%) in the lung or liver in 105 pts receiving RP1/2. All bleeding events occurred in pts receiving RP2 liver injections and resolved (2/3 events resolved by the following day). Conclusions: RP1/2 injections into visceral mets were well tolerated, with a comparable safety profile to liver and lung biopsies performed in other clinical settings. The observed RPx safety profile supports the incorporation of IT injections into deep visceral tumors as part of cancer therapy. Clinical trial information: NCT03767348 ; NCT04336241 . All-grade treatment-related adverse events (>15%). RP1 RP2 Monotherapy Combination therapy Monotherapy Combination therapy n (%) Injected visc mets (n = 11) Total (n = 19) Injected visc mets (n = 46) Total (n = 151) Injected visc mets (n = 14) Total (n = 20) Injected visc mets (n = 34) Total (n = 47) Pyrexia 9 (82) 12 (63) 22 (48) 51 (34) 6 (43) 9 (45) 18 (53) 25 (53) Chills 6 (55) 6 (32) 20 (44) 43 (28) 3 (21) 5 (25) 13 (38) 19 (40) Fatigue 3 (27) 7 (37) 8 (17) 39 (26) 1 (7) 3 (15) 4 (12) 7 (15) Influenza-like illness 1 (9) 2 (11) 12 (26) 31 (21) 0 0 2 (6) 8 (17) Nausea 1 (9) 1 (5) 13 (28) 26 (17) 1 (7) 1 (5) 5 (15) 8 (17) mets, metastases; visc, visceral.