60: Safety, efficacy, and biomarker assessment of RP1 in combination with nivolumab in patients with advanced skin cancers

Friday, March 24, 2023

10:54 AM – 11:04 AM

Location: Veterans Memorial Auditorium

Abstract Presenter(s)

Georgia Beasley, MD, MHSc (she/her/hers)

Associate Professor of Surgery, Associate Professor of Medicine, Co-director Duke Melanoma Program
Duke University
Durham, North Carolina, United States

Disclosure(s): No financial relationships to disclose

First Author(s)

Georgia Beasley, MD, MHSc (she/her/hers)

Associate Professor of Surgery, Associate Professor of Medicine, Co-director Duke Melanoma Program
Duke University
Durham, North Carolina, United States

Disclosure(s): No financial relationships to disclose

Author(s)

AV

Ari M. VanderWalde, MD, MPH, FACP

Research Faculty
West Cancer Center and Research Institute, United States

Disclosure information not submitted.
Tawnya L. Bowles, MD

Medical Director for Melanoma Services
Intermountain Medical Center
Murray, UT, United States

Disclosure information not submitted.
JS

Joseph J. Sacco, PhD, MBChB, MSc, MRCP

Consultant in Medical Oncology
Clatterbridge Cancer Centre and University of Liverpool, United States

Disclosure information not submitted.
JN

Jiaxin Niu, MD, PhD

Medical Oncologist
Banner MD Anderson Cancer Center, United States

Disclosure information not submitted.
KT

Katy K. Tsai, MD

Assistant Clinical Professor
Helen Diller Family Comprehensive Cancer Center Cutaneous Oncology, United States

Disclosure information not submitted.
JC

Jason A. Chesney, MD, PhD

Professor of Medicine
University of Louisville, Louisville, KY, USA, United States

Disclosure information not submitted.
BC

Bartosz Chmielowski, MD

Oncologist
University of California Los Angeles, United States

Disclosure information not submitted.
AS

Adel Samson, PhD

Clinical Associate Professor
University of Leeds, United Kingdom

Disclosure information not submitted.
TR

Terence Duane Rhodes, MD

Oncologist
Intermountain Medical Center
St. George, Utah, United States

Disclosure information not submitted.
GI

Gino K. In, MD, MPH

Assistant Professor of Medicine and Dermatology
University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA, United States

Disclosure information not submitted.
AP

Anna C. Pavlick, DO

Director of Melanoma and Cutaneous Oncology
Weill Cornell Medical College, United States

Disclosure information not submitted.
TW

Trisha M. Wise-Draper, MD, PhD

Associate Professor of Medicine
University of Cincinnati, United States

Disclosure information not submitted.
MS

Miguel F. Sanmamed, MD, PhD

Medical Oncologist
Clínica Universidad de Navarra, United States

Disclosure information not submitted.
JH

Jeannie Hou, MD

Vice President, Clinical Development
Replimune Inc., United States

Disclosure information not submitted.
MM

Mark R. Middleton, MD, PhD

Professor; Consultant Medical Oncologist
Churchill Hospital, United States

Disclosure information not submitted.
KH

Kevin Harrington, PhD, BSc, MBBS, MRCP, FRCP, FRCR

Head of the Division of Radiology and Imaging; Professor
Royal Marsden NHS Foundation Trust, The Institute of Cancer Research, United States

Disclosure information not submitted.
CL

Céleste Lebbe, MD, PhD

Professor
Université de Paris and CIC AP-HP Hôpital Saint Louis, United States

Disclosure information not submitted.
JM

Judith Michels, MD, PhD

Medical Oncologist
Institut Gustave Roussy, United States

Disclosure information not submitted.
MM

Mohammed M. Milhem, MBBS

Director, Melanoma Program
Holden Comprehensive Cancer Center, United States

Disclosure information not submitted.

Disclosure(s):

Georgia Beasley, MD, MHSc: No financial relationships to disclose

Introduction: RP1 is an oncolytic immunotherapy that expresses human GM-CSF and the fusogenic protein GALV-GP-R−. The objective of this study is to evaluate the safety and efficacy of RP1 combined with nivolumab (nivo), with relevant biomarker assessments, in a range of tumor types. Data reported here relate to study patients (pts) with melanoma (mel) and anti–PD-1 naïve non-melanoma skin cancers (NMSC).

Methods: RP1 is administered via intratumoral injection Q2W, first alone at a dose of 10⁶ PFU/mL and then starting with the 2^nd dose at 10⁷ PFU/mL in combination with nivo. Up to 8 total doses of RP1 and 2 years of nivo are given, with the option to re-initiate RP1 if clinically warranted.

Results: The ORR (CR+PR) was 62.5% in anti-PD1 naïve cutaneous mel (N=8), 37.5% for anti-PD1-resistant or anti-PD1+anti-CTLA-4 failed cutaneous mel (N=16), 100% and 20% for anti–PD-1 naïve (N=1) and anti-PD-1 resistant (N=5) mucosal melanoma, respectively. For anti–PD-1 naïve NMSC the ORR was 64.7% in CSCC (N=17) including 47.1% CR; 25% in BCC (N=4); 75% in MCC (N=4); and 66.6% in angiosarcoma (N=6). Though not yet mature, median DOR was 13.27 mos (current range 3.67-16.93 mos) for mel, and 7.32 mos (current range 1.88-23.11 mos) for anti–PD-1 naïve NMSC. Any grade TEAEs ( >25%) in all cohorts combined were chills (29.8%), pyrexia (29.8%), fatigue (28.6%), and pruritus (25%). Grade ≥3 TEAEs ( >5%) were disease progression and fatigue. No deaths related to RP1 were observed, with one death related to nivo (myocarditis). Immunohistochemistry demonstrated increases in CD8 T cell density, PD-L1 expression, and the CD8/foxp3+ cell ratio. Clinical responses were independent of baseline CD8 T cell infiltration, PD-L1 expression levels, and prior anti–PD-1 therapy.

Conclusions: 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.

Learning Objectives:

Describe key design features of the oncolytic immunotherapy RP1
Summarize the efficacy and safety of RP1 in combination with nivolumab in patients with melanoma and anti-PD1 naive non-melanoma skin cancers
Describe the key changes in immune biomarkers that were observed following treatment with RP1 plus nivolumab