Study of RP1 Monotherapy and RP1 in Combination With Nivolumab (IGNYTE)

An Open-Label, Multicenter, Phase 1/2 Study of RP1 as a Single Agent and in Combination With PD1 Blockade in Patients With Solid Tumors

RPL-001-16 is a Phase 1/2, open label, dose escalation and expansion clinical study of RP1 alone and in combination with nivolumab in adult subjects with advanced and/or refractory solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.

Study Overview

• Status: Recruiting
• Conditions: Cancer; NSCLC; Melanoma (Skin); Microsatellite Instability; Cutaneous Melanoma; Mismatch Repair Deficiency; Non-melanoma Skin Cancer
• Intervention / Treatment: Biological: RP1; Biological: nivolumab

Detailed Description

RP1 is a genetically modified herpes simplex type 1 virus that is designed to directly destroy tumors and to generate an anti-tumor immune response. This is a Phase 1/2, open label, multicenter, dose escalation and expansion, first-in-human (FIH) clinical study to evaluate the safety and tolerability, biodistribution, shedding, and preliminary efficacy of RP1 alone and in combination with nivolumab in adult subjects with advanced and/or refractory solid tumors. The study will include a dose escalation phase for single agent RP1, an expansion phase with a combination of RP1 and nivolumab and a Phase 2 portion in specified tumor types for the combination therapy.

• Study Type: Interventional
• Enrollment (Estimated): 340
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials at Replimune; Phone Number: 1-781-222-9570; Email: Clinicaltrials@replimune.com

Study Locations

• France
  • Besançon, France, 25000
    • Recruiting
    • CHU Besançon - Hôpital Jean Minjoz
    • Principal Investigator: Nardin Charlee, MD
  • Bordeaux, France, 33076
    • Recruiting
    • Institut Bergonié
    • Principal Investigator: Antoine Italiano, MD
  • Dijon, France, 21079
    • Recruiting
    • CHU Dijon
    • Principal Investigator: Sophie Dalac-Rat, MD
  • Lyon, France, 69373
    • Recruiting
    • Centre Léon Bérard Lyon
    • Contact: Mona AMINI-ADLE, MD
    • Principal Investigator: Mona AMINI-ADLE, MD
  • Marseille, France, 13005
    • Recruiting
    • Service de Dermatologie et Cancerologie Cutanee Hopital de la Timone
    • Principal Investigator: Caroline Gaudy, MD
  • Nice, France, 06200
    • Recruiting
    • CHU de Nice Hôpital l'Archet
    • Principal Investigator: Henri MONTAUDIE, MD
  • Paris, France, 75010
    • Recruiting
    • Hôpital Saint Louis APHP
    • Principal Investigator: Céleste Lebbe, MD
  • Villejuif, France, 94800
    • Recruiting
    • Institut Gustave Roussy
    • Principal Investigator: Judith Michels, MD
• Germany
  • Berlin, Germany, 12203
    • Recruiting
    • Charité (Campus Benjamin Franklin)
    • Principal Investigator: Sebastian Ochsenreither, MD
  • Essen, Germany, 45147
    • Recruiting
    • University Hospital Essen, Klinik für Dermatologie
    • Principal Investigator: Dirk Schadendorf, MD
  • Kiel, Germany, 24105
    • Recruiting
    • University of Kiel (UKSH), Dep. of Dermatology
    • Principal Investigator: Katharina Kahler, MD
  • Marburg, Germany, 35043
    • Recruiting
    • Uniklinik Marburg
    • Principal Investigator: Martin Gschnell, MD
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
    • Principal Investigator: Eva Couselo Munoz, MD
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic Barcelona
    • Principal Investigator: Ana Arance Fernandez, MD
  • Barcelona, Spain, 08908
    • Recruiting
    • Institut Catala D'Oncologia - Hospital Duran I
    • Principal Investigator: Juan Liberal Martin, MD
  • Madrid, Spain, 28027
    • Recruiting
    • Clinica Universidad de Navarra (Madrid)
    • Principal Investigator: Miguel Fernández de Sanmamed
  • Murcia, Spain, 30120
    • Recruiting
    • Hospital Universitario Virgen de la Arrixaca
    • Principal Investigator: Pablo Cerezuela, MD
  • Pamplona, Spain, 31008
    • Recruiting
    • Clinica Universitaria de Navarra
    • Principal Investigator: Miguel Gutiérrez Sanmamed, MD
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen Del Rocio
    • Principal Investigator: Ana Gill, MD
  • Valencia, Spain, 46014
    • Recruiting
    • Hospital General Universitario de Valencia
    • Principal Investigator: Alfonso Jaime Berrocal, MD
• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Royal Marsden Hospital
    • Principal Investigator: Kevin Harrington, BSc FRCP PhD
  • Southampton, United Kingdom, SO16 6YD
    • Recruiting
    • Southampton General Hospital
    • Principal Investigator: Ioannis Karydis, MD
  • England
    • Leeds, England, United Kingdom, LS97TF
      • Recruiting
      • University of Leeds- Teaching Hospital
      • Principal Investigator: Adel Samson, MD
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom
      • Recruiting
      • Oxford University Hospitals NHS Trust
      • Principal Investigator: Mark R Middleton, MD,PhD,FRCP
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 0YN
      • Recruiting
      • Beatson West of Scotland Cancer Center
      • Principal Investigator: Patricia Roxburgh, MD
  • Wirral
    • Bebington, Wirral, United Kingdom, CH634JY
      • Recruiting
      • The Clatterbridge Cancer Centre NHS Foundation Trust
      • Principal Investigator: Joseph Sacco, MRCP, PhD
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Active, not recruiting
      • University of Birmingham Alabama
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Recruiting
      • Banner MD Anderson Cancer Center
      • Principal Investigator: Jiaxin Niu, MD
      • Contact: Jenesse Moffett
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic
      • Principal Investigator: Mahesh Seetharam, MD
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • CARTI Cancer Center
      • Principal Investigator: Issam Makhoul, MD
  • California
    • La Jolla, California, United States, 92093
      • Active, not recruiting
      • UC San Diego
    • Los Angeles, California, United States, 90033
      • Recruiting
      • University of Southern California
      • Contact: Gino In, MD
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA
      • Contact: Danell Johnson
      • Principal Investigator: Bartosz Chmielowski, MD
    • Orange, California, United States, 92868
      • Recruiting
      • University of California, Irvine
      • Principal Investigator: John Fruehauf, MD
    • San Francisco, California, United States, 94115
      • Recruiting
      • University of California- San Francisco
      • Principal Investigator: Katy Tsai, MD
      • Contact: Melissa Chow
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • Sylvester Comprehensive Cancer Center- University of Miami
      • Principal Investigator: Estelamari Rodriguez, MD
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa-Cancer Center Research
      • Contact: Mariel McKay
      • Principal Investigator: Mohammed Milhem, MBBS
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • James Graham Brown Cancer Center- University of Louisville
      • Contact: Stacy Baum
      • Principal Investigator: Jason Chesney, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Principal Investigator: Robert McWilliams, MD
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Recruiting
      • Atlantic Health System
      • Contact: Eric Whitman, MD
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medical College
      • Principal Investigator: Anna Pavlick, DO
    • New York, New York, United States, 10016
      • Active, not recruiting
      • New York University Clinical Cancer Center
    • Rochester, New York, United States, 14642
      • Recruiting
      • University of Rochester Medical Center
      • Contact: Delaney Dretto
      • Contact: Janice Cifelli
      • Principal Investigator: Rachael Turner, MD
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke Cancer Center
      • Contact: Georgia Beasley, MD
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • University of Cincinnati Medical Center
      • Principal Investigator: Trisha Wise-Draper, MD
  • Oregon
    • Portland, Oregon, United States, 97213
      • Active, not recruiting
      • Providence Portland Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • MUSC Health
      • Contact: John Kaczmar, MD
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Recruiting
      • West Cancer Center
      • Contact: Alisa Harber
      • Principal Investigator: Ari VanderWalde, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
      • Principal Investigator: Michael Wong, MD
  • Utah
    • Murray, Utah, United States, 84107
      • Recruiting
      • Eccles Outpatient Care Center- Oncology Clinical Trials
      • Contact: Tawnya Bowles
      • Principal Investigator: Tawnya Bowles, MD
    • Saint George, Utah, United States, 84790
      • Recruiting
      • Intermountain Cancer Center- Saint George Cancer Center
      • Contact: Angi Cox
      • Principal Investigator: Terence Rhodes, MD
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Seattle Cancer Care Alliance- University of Washington
      • Contact: Katie Kim
      • Principal Investigator: Evan Hall, MD
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Active, not recruiting
      • University of Wisconsin-Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
• At least one measurable and injectable lesion
• Have provided a former tumor pathology specimen or be willing to supply a new tumor sample from a biopsy
• Have a predicted life expectancy of ≥ 3 months
• Measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
• Subjects with MSI-H or dMMR tumors: has diagnosis of MSI-H or metatstatic dMMR tumor (according to protocol definition) who has progressed on prior anti-PD1/PD-L1 therapy.
• Subjects with NMSC: has diagnosis of locally advanced or metastatic NMSC that are not considered treatable by surgery including basal cell carcinoma, cutaneous squamous cell carcinoma, basosquamous carcinoma, Merkel cell carcinoma and other non-melanoma skin cancers (per protocol). Patients must have received 8 weeks of anti-PD1/PD-L1 as their last line of therapy and progressed while on treatment.
• Subjects with anti-PD1 failed cutaneous melanoma: has confirmed progressive disease while on anti-PD1 treatment for at least 8 weeks and documented BRAF mutation status
• Subjects with anti-PD1 failed NSCLC: must have failed prior treatment, including PD1/PD-L1 directed therapy administered either as monotherapy or in combination with platinum-based chemotherapy or anti-CTLA-4. The most recent treatment given must have included an anti-PD1/PD-L1 directed therapy with radiologic disease progression on or after treatment.

Exclusion Criteria:

• Prior treatment with an oncolytic therapy
• History of viral infections according to the protocol
• Prior complications with herpes infections
• Chronic use of anti-virals
• Uncontrolled/untreated brain metastasis
• History of interstitial lung disease
• History of non-infectious pneumonitis
• History of clinically significant cardiovascular disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation of RP1 by intratumoral (IT) injection in superficial tumors; Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors	Biological: RP1; Genetically modified herpes simplex type 1 virus
Experimental: Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors; Dose escalation of RP1 alone in 3 cohorts with IT injections in deep/visceral tumors	Biological: RP1; Genetically modified herpes simplex type 1 virus
Experimental: Dose expansion of RP1 and nivolumab (IV) in superficial tumors; Doses of RP1 (IT) in superficial tumors with nivolumab (IV)	Biological: RP1; Genetically modified herpes simplex type 1 virus; Biological: nivolumab; anti-PD-1 monoclonal antibody; Other Names: Opdivo
Experimental: Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors; Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)	Biological: RP1; Genetically modified herpes simplex type 1 virus; Biological: nivolumab; anti-PD-1 monoclonal antibody; Other Names: Opdivo
Experimental: RP1 (IT) and nivolumab (IV) in melanoma; Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma	Biological: RP1; Genetically modified herpes simplex type 1 virus; Biological: nivolumab; anti-PD-1 monoclonal antibody; Other Names: Opdivo
Experimental: RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors; Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with MSI-H or dMMR solid tumors	Biological: RP1; Genetically modified herpes simplex type 1 virus; Biological: nivolumab; anti-PD-1 monoclonal antibody; Other Names: Opdivo
Experimental: RP1 (IT) and nivolumab (IV) in NMSC; Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer	Biological: RP1; Genetically modified herpes simplex type 1 virus; Biological: nivolumab; anti-PD-1 monoclonal antibody; Other Names: Opdivo
Experimental: RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma; Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with cutaneous melanoma who have been previously treated with anti-PD1 therapy	Biological: RP1; Genetically modified herpes simplex type 1 virus; Biological: nivolumab; anti-PD-1 monoclonal antibody; Other Names: Opdivo
Experimental: RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC; Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer who have been previously treated with anti-PD1/PD-L1 therapy	Biological: RP1; Genetically modified herpes simplex type 1 virus; Biological: nivolumab; anti-PD-1 monoclonal antibody; Other Names: Opdivo
Experimental: RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC; Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non small cell lung cancer who have been previously treated with anti-PD1/PD-L1 therapy	Biological: RP1; Genetically modified herpes simplex type 1 virus; Biological: nivolumab; anti-PD-1 monoclonal antibody; Other Names: Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of adverse events (AEs)	Percentage of subjects with adverse events (AEs)	26 months
Percentage of serious adverse events (SAEs)	Percentage of subjects with serious adverse events (SAEs)	26 months
Percentage of dose limiting toxicities (DLTs)	Percentage of subjects with dose limiting toxicities (DLTs)	26 months
Percentage of overall response rate (ORR)	Percentage of overall response rate (ORR) for all participants	26 months
Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1	Assess the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1 based on the safety and response data collected during Phase 1 Escalation	20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of biologic activity	Percentage of subjects with biological activity determined by tumor biopsies and biomarker data	20 weeks
Percentage subjects with detectable RP1	Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of RP1	20 weeks
Percentage of complete response (CR)	Percentage of subjects with a complete response (CR)	26 months
Median duration of response	Median duration of response of subjects	26 months
Median progression-free survival	Median duration of progression-free survival of subjects	26 months
Median overall survival	Median overall survival rate of subjects	26 months

Collaborators and Investigators

• Sponsor: Replimune Inc.
• Investigators: Study Director: Jeannie Hou, MD, Replimune Inc.

Publications and helpful links

General Publications

• Thomas S, Kuncheria L, Roulstone V, Kyula JN, Mansfield D, Bommareddy PK, Smith H, Kaufman HL, Harrington KJ, Coffin RS. Development of a new fusion-enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1. J Immunother Cancer. 2019 Aug 10;7(1):214. doi: 10.1186/s40425-019-0682-1.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2017
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: December 5, 2018
• First Submitted That Met QC Criteria: December 5, 2018
• First Posted (Actual): December 6, 2018

Study Record Updates

• Last Update Posted (Actual): August 2, 2023
• Last Update Submitted That Met QC Criteria: August 1, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Cutaneous Melanoma; Oncolytic virus; Oncolytic Immuno-gene therapy; Non-melanoma Skin Cancer; Anti-PD1 failed; Melanoma (skin)
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Genomic Instability; Melanoma; Skin Neoplasms; Microsatellite Instability; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: RPL-001-16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No