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

NCT03767348 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RPL-001-162016-004548-122024-511728-15-00
• Study Type: interventional
• Target: 340
• Locations: 5 countries
• Sites: 51

Brief Summary

The Phase 2 study is a multicenter, open-label study of RP1 to further investigate safety and to estimate the efficacy of RP1 at the RP2D in combination with nivolumab in patients with Stage IIIb-IV unresectable melanoma, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, non-melanoma skin cancer (NMSC), and non-small cell lung cancer (NSCLC).

Conditions

Non-melanoma Skin Cancer (NMSC); Cutaneous Melanoma; Non-Small Cell Lung Cancer (NSCLC); Microsatellite Instability-High (MSI-H)

Keywords

RPL-001-16; Stage IIIb-IV Unresectable Melanoma; Non-melanoma Skin Cancer; Mismatch Repair Deficient (dMMR) Solid Tumors

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (6)

• Percentage of biologic activity

  20 weeks

• Percentage subjects with detectable RP1

  20 weeks

• Percentage of complete response (CR)

  26 months

• Median duration of response

  26 months

• Median progression-free survival

  26 months

Study Arms (10)

Dose escalation of RP1 by intratumoral (IT) injection in superficial tumors

EXPERIMENTAL

anti-PD-1 monoclonal antibody

Biological: RP1

Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors

EXPERIMENTAL

Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors

Biological: RP1

Dose expansion of RP1 and nivolumab (IV) in superficial tumors

EXPERIMENTAL

Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors

Biological: RP1; Biological: nivolumab

Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors

EXPERIMENTAL

Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)

Biological: RP1; Biological: nivolumab

RP1 (IT) and nivolumab (IV) in melanoma

EXPERIMENTAL

Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma

Biological: RP1; Biological: nivolumab

RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors

EXPERIMENTAL

Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with MSI-H or dMMR solid tumors

Biological: RP1; Biological: nivolumab

RP1 (IT) and nivolumab (IV) in NMSC

EXPERIMENTAL

Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer

Biological: RP1; Biological: nivolumab

RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma

EXPERIMENTAL

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; Biological: nivolumab

RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC

EXPERIMENTAL

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; Biological: nivolumab

RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC

EXPERIMENTAL

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; Biological: nivolumab

Interventions

RP1 BIOLOGICAL

Genetically modified herpes simplex type 1 virus

Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors; Dose escalation of RP1 by intratumoral (IT) injection in superficial tumors; Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors; Dose expansion of RP1 and nivolumab (IV) in superficial tumors; RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors; RP1 (IT) and nivolumab (IV) in NMSC; RP1 (IT) and nivolumab (IV) in melanoma; RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma; RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC; RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC

nivolumab BIOLOGICAL

anti-PD-1 monoclonal antibody

Also known as: Opdivo

Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors; Dose expansion of RP1 and nivolumab (IV) in superficial tumors; RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors; RP1 (IT) and nivolumab (IV) in NMSC; RP1 (IT) and nivolumab (IV) in melanoma; RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma; RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC; RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Replimune Inc.: lead
• Bristol-Myers Squibb: collaborator

Study Sites (51)

University of Birmingham Alabama

Birmingham, Alabama, 35294, United States

Location

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Carti Cancer Center

Little Rock, Arkansas, 72205, United States

Location

UC San Diego

La Jolla, California, 92093, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

University of California, Irvine

Orange, California, 92868, United States

Location

University of California- San Francisco

San Francisco, California, 94115, United States

Location

Sylvester Comprehensive Cancer Center- University of Miami

Miami, Florida, 33136, United States

Location

University of Iowa-Cancer Center Research

Iowa City, Iowa, 52242, United States

Location

James Graham Brown Cancer Center- University of Louisville

Louisville, Kentucky, 40202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

New York University Clinical Cancer Center

New York, New York, 10016, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

MUSC Health

Charleston, South Carolina, 29425, United States

Location

West Cancer Center

Germantown, Tennessee, 38138, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Eccles Outpatient Care Center- Oncology Clinical Trials

Murray, Utah, 84107, United States

Location

Intermountain Cancer Center- Saint George Cancer Center

St. George, Utah, 84790, United States

Location

Seattle Cancer Care Alliance- University of Washington

Seattle, Washington, 98109, United States

Location

University of Wisconsin-Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

CHU Besancon - Hopital Jean Minjoz

Besançon, 25000, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

CHU Dijon

Dijon, 21079, France

Location

Centre Léon Bérard Lyon

Lyon, 69373, France

Location

Service de Dermatologie et Cancerologie Cutanee Hopital de la Timone

Marseille, 13005, France

Location

CHU de Nice Hôpital l'Archet

Nice, 06200, France

Location

Hôpital Saint Louis APHP

Paris, 75010, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

Charité (Campus Benjamin Franklin)

Berlin, 12203, Germany

Location

University Hospital Essen, Klinik für Dermatologie

Essen, 45147, Germany

Location

University of Kiel (UKSH), Dep. of Dermatology

Kiel, 24105, Germany

Location

Uniklinik Marburg

Marburg, 35043, Germany

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic Barcelona

Barcelona, 08036, Spain

Location

Clínica Universidad de Navarra (Madrid)

Madrid, 28027, Spain

Location

Hospital Universitario Virgen de la Arrixaca

Murcia, 30120, Spain

Location

Clinica Universitaria de Navarra

Pamplona, 31008, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

University of Leeds- Teaching Hospital

Leeds, England, LS97TF, United Kingdom

Location

Oxford University Hospitals NHS Trust

Oxford, Oxfordshire, United Kingdom

Location

Beatson West of Scotland Cancer Center

Glasgow, Scotland, G12 0YN, United Kingdom

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Wirral, CH634JY, United Kingdom

Location

Royal Marsden Hospital

London, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (2)

• Wong MK, Milhem MM, Sacco JJ, Michels J, In GK, Munoz Couselo E, Schadendorf D, Beasley GM, Niu J, Chmielowski B, Wise-Draper TM, Bowles TL, Tsai KK, Lebbe C, Gaudy-Marqueste C, Middleton MR, Skolariki A, Samson A, Chesney JA, VanderWalde AM, Zakharia Y, Harrington KJ, Appleton E, Bommareddy PK, Zhu J, Viana M, Hou JW, Coffin RS, Robert C. RP1 Combined With Nivolumab in Advanced Anti-PD-1-Failed Melanoma (IGNYTE). J Clin Oncol. 2025 Nov 20;43(33):3589-3599. doi: 10.1200/JCO-25-01346. Epub 2025 Jul 8.

  PMID: 40627813 DERIVED

• 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.

  PMID: 31399043 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Melanoma; Turcot syndrome

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jeannie Hou, MD

  Replimune Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2018
• First Posted: December 6, 2018
• Study Start: September 20, 2017
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (6); DE (4); FR (8); US (26); ES (7)