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

NCT ID: NCT03767348

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

340 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-20

Study Completion Date

2028-12-31

Brief Summary

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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).

Detailed Description

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Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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

anti-PD-1 monoclonal antibody

Group Type EXPERIMENTAL

RP1

Intervention Type BIOLOGICAL

Genetically modified herpes simplex type 1 virus

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

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

Group Type EXPERIMENTAL

RP1

Intervention Type BIOLOGICAL

Genetically modified herpes simplex type 1 virus

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

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

Group Type EXPERIMENTAL

RP1

Intervention Type BIOLOGICAL

Genetically modified herpes simplex type 1 virus

nivolumab

Intervention Type BIOLOGICAL

anti-PD-1 monoclonal antibody

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

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

Group Type EXPERIMENTAL

RP1

Intervention Type BIOLOGICAL

Genetically modified herpes simplex type 1 virus

nivolumab

Intervention Type BIOLOGICAL

anti-PD-1 monoclonal antibody

RP1 (IT) and nivolumab (IV) in melanoma

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

Group Type EXPERIMENTAL

RP1

Intervention Type BIOLOGICAL

Genetically modified herpes simplex type 1 virus

nivolumab

Intervention Type BIOLOGICAL

anti-PD-1 monoclonal antibody

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

Group Type EXPERIMENTAL

RP1

Intervention Type BIOLOGICAL

Genetically modified herpes simplex type 1 virus

nivolumab

Intervention Type BIOLOGICAL

anti-PD-1 monoclonal antibody

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

Group Type EXPERIMENTAL

RP1

Intervention Type BIOLOGICAL

Genetically modified herpes simplex type 1 virus

nivolumab

Intervention Type BIOLOGICAL

anti-PD-1 monoclonal antibody

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

Group Type EXPERIMENTAL

RP1

Intervention Type BIOLOGICAL

Genetically modified herpes simplex type 1 virus

nivolumab

Intervention Type BIOLOGICAL

anti-PD-1 monoclonal antibody

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

Group Type EXPERIMENTAL

RP1

Intervention Type BIOLOGICAL

Genetically modified herpes simplex type 1 virus

nivolumab

Intervention Type BIOLOGICAL

anti-PD-1 monoclonal antibody

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

Group Type EXPERIMENTAL

RP1

Intervention Type BIOLOGICAL

Genetically modified herpes simplex type 1 virus

nivolumab

Intervention Type BIOLOGICAL

anti-PD-1 monoclonal antibody

Interventions

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RP1

Genetically modified herpes simplex type 1 virus

Intervention Type BIOLOGICAL

nivolumab

anti-PD-1 monoclonal antibody

Intervention Type BIOLOGICAL

Other Intervention Names

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Opdivo

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Replimune Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jeannie Hou, MD

Role: STUDY_DIRECTOR

Replimune Inc.

Locations

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University of Birmingham Alabama

Birmingham, Alabama, United States

Site Status

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

Mayo Clinic

Phoenix, Arizona, United States

Site Status

Carti Cancer Center

Little Rock, Arkansas, United States

Site Status

UC San Diego

La Jolla, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

UCLA

Los Angeles, California, United States

Site Status

University of California, Irvine

Orange, California, United States

Site Status

University of California- San Francisco

San Francisco, California, United States

Site Status

Sylvester Comprehensive Cancer Center- University of Miami

Miami, Florida, United States

Site Status

University of Iowa-Cancer Center Research

Iowa City, Iowa, United States

Site Status

James Graham Brown Cancer Center- University of Louisville

Louisville, Kentucky, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

New York University Clinical Cancer Center

New York, New York, United States

Site Status

Weill Cornell Medical College

New York, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Duke Cancer Center

Durham, North Carolina, United States

Site Status

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status

Providence Portland Medical Center

Portland, Oregon, United States

Site Status

MUSC Health

Charleston, South Carolina, United States

Site Status

West Cancer Center

Germantown, Tennessee, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Eccles Outpatient Care Center- Oncology Clinical Trials

Murray, Utah, United States

Site Status

Intermountain Cancer Center- Saint George Cancer Center

St. George, Utah, United States

Site Status

Seattle Cancer Care Alliance- University of Washington

Seattle, Washington, United States

Site Status

University of Wisconsin-Carbone Cancer Center

Madison, Wisconsin, United States

Site Status

CHU Besancon - Hopital Jean Minjoz

Besançon, , France

Site Status

Institut Bergonié

Bordeaux, , France

Site Status

CHU Dijon

Dijon, , France

Site Status

Centre Léon Bérard Lyon

Lyon, , France

Site Status

Service de Dermatologie et Cancerologie Cutanee Hopital de la Timone

Marseille, , France

Site Status

CHU de Nice Hôpital l'Archet

Nice, , France

Site Status

Hôpital Saint Louis APHP

Paris, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Charité (Campus Benjamin Franklin)

Berlin, , Germany

Site Status

University Hospital Essen, Klinik für Dermatologie

Essen, , Germany

Site Status

University of Kiel (UKSH), Dep. of Dermatology

Kiel, , Germany

Site Status

Uniklinik Marburg

Marburg, , Germany

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Clinic Barcelona

Barcelona, , Spain

Site Status

Clínica Universidad de Navarra (Madrid)

Madrid, , Spain

Site Status

Hospital Universitario Virgen de la Arrixaca

Murcia, , Spain

Site Status

Clinica Universitaria de Navarra

Pamplona, , Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Hospital General Universitario de Valencia

Valencia, , Spain

Site Status

University of Leeds- Teaching Hospital

Leeds, England, United Kingdom

Site Status

Oxford University Hospitals NHS Trust

Oxford, Oxfordshire, United Kingdom

Site Status

Beatson West of Scotland Cancer Center

Glasgow, Scotland, United Kingdom

Site Status

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Wirral, United Kingdom

Site Status

Royal Marsden Hospital

London, , United Kingdom

Site Status

Southampton General Hospital

Southampton, , United Kingdom

Site Status

Countries

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United States France Germany Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 40627813 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31399043 (View on PubMed)

Other Identifiers

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2016-004548-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-511728-15-00

Identifier Type: CTIS

Identifier Source: secondary_id

RPL-001-16

Identifier Type: -

Identifier Source: org_study_id