Abstract
Updated results from the skin cancer cohorts from an ongoing phase 1/2 multicohort study of RP1, an enhanced potency oncolytic HSV, combined with nivolumab (IGNYTE)
Journal of clinical oncology, Vol.40(16_suppl), pp.9553-9553
06/01/2022
DOI: 10.1200/JCO.2022.40.16_suppl.9553
Abstract
9553
Background: RP1 is an enhanced potency oncolytic version of HSV1 that expresses human GM-CSF and the fusogenic protein GALV-GP R-. IGNYTE is a multicohort phase 1/2 study that evaluates the safety and efficacy of RP1 in combination with nivo (NCT03767348) in a range of tumor types. Preliminary data demonstrated a durable anti-tumor activity and tolerability for RP1+nivo. Here, we present updated results from the initial and melanoma (mel) and anti-PD1 naïve non-melanoma skin cancer (NMSC) cohorts with RP1+nivo. Methods: RP1 is administered via intratumoral injection Q2W, up to 10 mL/visit, first alone at a dose of 10
6
PFU/mL and then starting with the 2
nd
dose at 10
7
PFU/mL in combination with nivo (240 mg IV Q2W for 4 months (mos) then 480 mg IV Q4W up to 2 yrs) for up to 8 doses, with the option to re-initiate RP-1. Eligible patients (pts) must have at least one measurable & injectable tumor of ≥ 1 cm, ECOG 0-1, and no prior oncolytic therapy. For mel, both anti-PD1 naïve and failed pts were eligible, for NMSC pts who were anti-PD1 naïve. Results: As of data extraction on January 31, 2022, 13/36 pts with mel (36.1%) and 19/31 pts with NMSC (61.3%) had a best response of PR or CR. For mel this was 5/8 (62.5%), 6/16 (37.5%), 0/6 and 2/6 (33.3%) for pts with anti-PD1 naïve cutaneous, anti-PD1/anti-PD1+anti-CTLA-4 failed cutaneous, uveal and mucosal mel respectively. For the anti-PD1 naïve NMSC this included 11/17 (64.7%), 1/4 (25%), 3/4 (75%) and 4/6 (66.6%) patients with CSCC, BCC, MCC and angiosarcoma respectively, including 8/17 (47.1%) being CR for CSCC. Current immature median DOR was 13.27 mos (current range 3.67-16.93 mos) for mel, and 7.32 mos (current range 1.88-23.11mos) for anti-PD1 naïve NMSC. Any grade TEAE ( > 25%) in all cohorts combined were fatigue, nausea, pyrexia, chills, diarrhoea, pruritus, and influenza-like illness. TEAE ≥grade 3 ( > 5%) were disease progression and fatigue. No deaths related to RP1 was observed, with one death related to nivo (myocarditis). Biomarker data from paired biopsies indicated robust T cell infiltration and an increase in tumor inflammation gene signature post-treatment. Clinical responses observed were independent of baseline tumor PD-L1 expression status. Conclusions: RP1 in combination with nivo provides a durable anti-tumor activity in pts with skin cancers, including anti-PD1 failed and anti-PD1/anti-CTLA-4 failed mel. The combination continued to be generally well tolerated with no new safety signals identified. Based on this data, enrollment into both a registration-directed cohort of pts who have anti-PD1 failed cutaneous mel (n = 125) and a cohort of pts with anti-PD1 failed NMSC (n = 30) is ongoing. Up-to-date data from this ongoing trial will be reported at the conference. A randomized Ph2 trial of RP1+cemiplimab vs. cemiplimab alone in anti-PD1 naïve NMSC is also underway (NCT04050436). Clinical trial information: NCT03767348.
Details
- Title: Subtitle
- Updated results from the skin cancer cohorts from an ongoing phase 1/2 multicohort study of RP1, an enhanced potency oncolytic HSV, combined with nivolumab (IGNYTE)
- Creators
- Mohammed M. Milhem - University of IowaAri M. Vanderwalde - West Cancer CenterTawnya Lynn Bowles - Intermountain Medical CenterJoseph J. Sacco - University of LiverpoolJiaxin Niu - Banner MD Anderson, Phoenix, AZ;Katy K. Tsai - University of California, San FranciscoJason Alan Chesney - University of LouisvilleBartosz Chmielowski - University of California, Los AngelesAdel Samson - University of LeedsTerence Duane Rhodes - CAMC Health System, Charleston, WV;Gino Kim In - University of Southern CaliforniaAnna C. Pavlick - NYU Langone HealthTrisha Michel Wise-Draper - University of CincinnatiMiguel F. Sanmamed - Clinica Universidad de NavarraPraveen Bommareddy - Replimune Inc, Woburn, MA;Junhong Zhu - Replimune Group Inc, Woburn, MARobert S. Coffin - Biovex LTD, Abingdon Oxon, United Kingdom;Kevin Joseph Harrington - The Royal Marsden//The Institute of Cancer Research NIHR Biomedical Research Centre, London, United Kingdom;Mark R. Middleton - Churchill Hospital
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.40(16_suppl), pp.9553-9553
- DOI
- 10.1200/JCO.2022.40.16_suppl.9553
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Grant note
- name: Replimune Group Inc.
- Language
- English
- Date published
- 06/01/2022
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984363289002771
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