vusolimogene oderparepvec (RP1)

P1, N=25, Recruiting, Yana Najjar | Not yet recruiting --> Recruiting

P3, N=400, Not yet recruiting, Replimune Inc.

P1, N=25, Not yet recruiting, Yana Najjar

P1/2, N=65, Recruiting, Replimune Inc. | Phase classification: P1b/2 --> P1/2

A total of 91 pts are included in this analysis (initial melanoma cohort, 16 pts; R-D cohort, 75 pts; data cut: Dec 30, 2022). The overall objective response rate (ORR) was 37.4% (initial cohort, 37.5%; R-D cohort, 37.3%), and 18.7% of pts achieved complete response (CR; Table). The response rates seen were also encouraging when evaluated by prior anti–PD-1 therapy setting and disease stage (Table).

P1/2, N=51, Not yet recruiting, Institut Curie

This is the first trial demonstrating single-agent RP1 antitumor effect in immunocompromised pts. RP1 monotherapy was well tolerated and the safety profile was similar to non-immunocompromised pts with advanced SC (IGNYTE study). Of note, no immune-mediated adverse events or evidence of allograft rejection were observed.

RP1+nivo induced deep and durable antitumor activity in patients with advanced skin cancers, including anti–PD-1 and anti–PD-1/anti–CTLA-4–failed melanoma. The combination was generally well tolerated, consistent with prior data. Enrollment into a registration-directed cohort of patients with anti–PD-1–failed cutaneous melanoma (n=125) and a cohort with anti–PD-1–failed NMSC (n=30) is ongoing.

RP1 + nivo induced a deep and durable antitumor activity in pts with advanced skin cancers, including anti-PD-1 and anti-PD-1/anti-CTLA-4 failed mel. The combination was generally well tolerated, consistent with prior data. Enrollment into a registration-directed cohort of pts with anti-PD-1 failed cutaneous mel (n=125) and a cohort with anti-PD-1 failed NMSC (n=30) is ongoing.

A notable reversal of CD8 T cell exclusion was observed in a melanoma patient who failed prior ipilimumab and nivo treatment. The data indicate the potential for broad utility of RP1 in a range of tumor types, including in patients with primary or acquired resistance to immune checkpoint blockade. Trial Registration NCT03767348

TBD/NA (Trial-in-Progress)

The tumor inflammation signature score (TIS) was also calculated.Preliminary Phase 1/2 biomarker data from paired tumor biopsies include the following: Immunohistochemistry for CD8 and PD-L1 (n=30) indicated robust and increased infiltration of CD8+ T cells and PD-L1 expression, both after combined treatment with RP1 and nivolumab and after single agent RP2 across different tumor types, and including reversal of T cell exclusion following prior combined treatment with ipilimumab and nivolumab in melanoma. Consistent with the pre-clinical data, preliminary clinical biomarker data indicate substantial increase in CD8 T cell infiltration and PD-L1 expression, as well as increased TIS score in the majority of patients treated with RP2 alone or RP1 and nivolumab combination. Particularly marked effects were seen in some patients with clinical responses which occurred independent of both baseline PD-L1 and prior anti-PD1 therapy status, which suggests potential broad utility of the RP1/2 treatment approach in igniting an anti-tumor immune response. Tumor mutation burden analysis and T cell receptor sequencing are currently underway and further updates of the dataset will be presented.

Co-treatment with RP1 and an anti-mouse PD-1 antibody increased anti-tumor effects and the levels of CD3+ cells in uninjected tumors. Data from detailed RNAseq transcriptional analyses from injected and uninjected tumors will also be presented.

P2, N=300, Recruiting, Replimune Inc. | Phase classification: P1/2 --> P2 | Trial completion date: Dec 2021 --> Nov 2024 | Trial primary completion date: Nov 2021 --> Nov 2024

P1b, N=30, Recruiting, Replimune Inc. | Not yet recruiting --> Recruiting

RP1 and nivo has continued to be well tolerated, with promising signs of efficacy in patients with skin cancers, including with anti-PD1 refractory disease. These data support the further development of RP1 combined with anti-PD1 blockade. Research Funding: Replimune

P1/2, N=281, Recruiting, Replimune Inc. | N=168 --> 281