Study of RP3 Monotherapy and RP3 in Combination With Nivolumab in Patients With Solid Tumours

February 25, 2026 updated by: Replimune Inc.

An Open-Label, Multicenter, Phase 1 Study of RP3 as a Single Agent and in Combination With PD-1 Blockade in Patients With Solid Tumors

This is a Phase 1, multicenter, open label, single agent dose escalation and combination treatment study of RP3 in adult participants with advanced solid tumors, to evaluate the safety and tolerability of RP3 both as a single agent and in combination with anti-PD1 therapy and to determine the recommended Phase 2 dose (RP2D) of RP3.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

RP3 is a genetically modified herpes simplex type 1 virus (HSV-1) that expresses exogenous genes (anti-CTLA-4 antibody, CD40 ligand and h4-1BBL) designed to directly destroy tumors and generate an anti-tumor immune response

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
123

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • France
      • Villejuif, France, 94805
        • Laboratoire de Recherche Translationnelle en Immunotherapie (LRTI), Gustave Roussy
  • Greece
      • Athens, Greece, 12462
        • University General Hospital Attikon
      • Athens, Greece, 11527
        • University of Athens
  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clinic Barcelona
      • Barcelona, Spain, 08035
        • Vall d'Hebron Hospital Hospital Universitario Vall d´Hebron (Vall d'Hebron University Hospital)
      • Madrid, Spain, 28050
        • START Madrid CIO Clara Campal, Hospital Universitario HM Sanchinarro Unidad de Ensayos Fase I Panta 3
      • Valencia, Spain, 46010
        • Hospital Clinico Universitario de Valencia
  • United Kingdom
      • London, United Kingdom, SW3 6JJ
        • The Royal Marsden NHS Foundation Trust
      • Oxford, United Kingdom, OX3 9DU
        • Churchill Hospital
    • Merseyside
      • Bebington, Merseyside, United Kingdom, CH63 4JY
        • The Clatterbridge Cancer Centre NHS Foundation Trust
  • United States
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Hillman Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • Md Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with advanced or metastatic non-neurological solid tumors, who have progressed on standard therapy or cannot tolerate standard therapy, or for whom there is no standard therapy preferred to enrollment in a clinical study
  • All patients must consent to provide archival tumor biopsy samples within 12 months, or a fresh tumor biopsy is needed. Patients must also consent to provide on treatment biopsies as per protocol
  • At least one measurable tumor ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes)
  • At least one injectable tumor ≥ 1 cm in longest diameter or injectable tumors which in aggregate are ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1

Note: Predefined inclusion criteria may apply for each additional expansion cohort.

Exclusion Criteria:

  • Prior treatment with an oncolytic virus therapy
  • History of viral infections according to the protocol
  • Systemic infection requiring intravenous (IV) antibiotics
  • Active significant herpetic infections or prior complications of HSV-1 infection (e.g., herpetic keratitis or encephalitis)

  • Requires intermittent or chronic use of systemic antivirals

    a. Hepatocellular carcinoma patients with a diagnosis of hepatitis B must be off antiviral therapy for at least 4 weeks prior to enrollment . Hepatocellular carcinoma patients with a history of or ongoing hepatitis C infection must have completed treatment for hepatitis C at least 1 month prior to study enrollment and hepatitis

  • History of interstitial lung disease
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis

Additional Exclusion Criteria for Patients Enrolled in Part 2 (Expansion Cohorts):

  • History of life-threatening toxicity related to prior immune treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
  • Treatment with botanical preparations within 2 weeks prior to treatment.
  • Active, known, or suspected autoimmune disease requiring systemic treatment.
  • History of interstitial lung disease.
  • Severe hypersensitivity to another monoclonal antibody.
  • Has received prior radiotherapy within 2 weeks of start of study treatment.
  • Has received a live vaccine within 28 days prior to the first dose of study treatment.
  • History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • History of myocarditis or congestive heart failure within 6 months of screening.
  • Has a serious or uncontrolled medical disorder.
  • Has a QT interval corrected for heart rate using Fridericia's formula (QTcF) > 480 msec, except for right bundle branch block.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dose escalation of RP3 - superficial and/or deep/visceral tumors
Dose escalation of RP3 alone in 2 cohorts with intratumoral (IT) injections including use of imaging guided injection for deep tumors.
Biological: RP3
Genetically modified HSV-1
Experimental: Dose combination of RP3 and anti-PD1 therapy - superficial and/or deep/visceral tumors
Dose combination of RP3 and anti-PD1 therapy. IT injections of RP3 including use of imaging guided injection for deep tumors.
Biological: RP3
Genetically modified HSV-1
Biological: Nivolumab
anti-PD1 monoclonal antibody
Experimental: Seronegative cohort
Doses of RP3 (IT) in HSV seronegative participants.
Biological: RP3
Genetically modified HSV-1

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of dose limiting toxicities (DLTs) during the DLT period
Time Frame: From Day 1 up to 30 days after last dose
Percentage of participants with DLTs
From Day 1 up to 30 days after last dose
Incidence and severity of treatment emergent adverse events (TEAEs)
Time Frame: From Day 1 up to 60 days after last dose
Percentage of participants with TEAEs
From Day 1 up to 60 days after last dose
Incidence and severity of serious adverse events (SAEs)
Time Frame: From Day 1 up to 60 days after last dose
Percentage of participants with SAEs
From Day 1 up to 60 days after last dose
Incidence of TEAEs ≥ Grade 3
Time Frame: From Day 1 up to 60 days after last dose
Percentage of participants with TEAEs ≥ Grade 3
From Day 1 up to 60 days after last dose
Percentage of events requiring withdrawal
Time Frame: From Day 1 up to last dose (up to 8 weeks in escalation phase and up to 2 years in combination phase)
Percentage of participants experiencing events requiring withdrawal from treatment.
From Day 1 up to last dose (up to 8 weeks in escalation phase and up to 2 years in combination phase)
Recommended phase 2 dose (RP2D) of RP3
Time Frame: 7 months
RP2D of RP3 based on the safety and response data collected during the dose escalation phase (Part 1)
7 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of biologic activity
Time Frame: From Day 1 to 24 months following the last dose in dose escalation. From Day 1 to 100 days following the last dose in dose combination
Percentage of participants with biological activity as assessed by individual tumor responses (including erythema, necrosis, and/or inflammation and changes in tumor sizes, in injected and uninjected tumors).
From Day 1 to 24 months following the last dose in dose escalation. From Day 1 to 100 days following the last dose in dose combination
Incidence of clearance of RP3 from blood and urine
Time Frame: From Day 1 to 60 days following the last dose in dose escalation. From Day 1 to 100 days following the last dose in dose combination
Incidence of clearance of RP3 from blood and urine before and after each injection
From Day 1 to 60 days following the last dose in dose escalation. From Day 1 to 100 days following the last dose in dose combination
Percentage of participants with detectable RP3.
Time Frame: From Day 1 to 60 days following the last dose in dose escalation. From Day 1 to 100 days following the last dose in dose combination
Data gathered from blood, urine, swabs of injection site, dressing and oral mucosa to determine the shedding and biodistribution of RP3
From Day 1 to 60 days following the last dose in dose escalation. From Day 1 to 100 days following the last dose in dose combination
Change in HSV-1 antibody levels
Time Frame: From Day 1 to Day 43
Change in HSV-1 antibody levels during treatment compared to baseline
From Day 1 to Day 43
Percentage of HSV-1 seronegative patients with TEAEs
Time Frame: From Day 1 to 60 days following last dose in dose escalation. From Day 1 to 100 days post last dose in dose combination
Percentage of HSV-1 seronegative patients with TEAEs
From Day 1 to 60 days following last dose in dose escalation. From Day 1 to 100 days post last dose in dose combination
Percentage of objective overall response rate (ORR)
Time Frame: Up to 3 years since first patient in
Percentage of ORR
Up to 3 years since first patient in
Median duration of response
Time Frame: Up to 3 years since first patient in
Median duration of response of participants
Up to 3 years since first patient in
Percentage of complete response (CR)
Time Frame: From Day 1 up to last dose (Day 57 or 8th Re-initiation dose in escalation phase and up to 2 years for combination phase)
Percentage of participants with a CR
From Day 1 up to last dose (Day 57 or 8th Re-initiation dose in escalation phase and up to 2 years for combination phase)
Percentage of partial response (PR)
Time Frame: From Day 1 up to last dose (Day 57 or 8th Re-initiation dose in escalation phase and up to 2 years for combination phase)
Percentage of participants with a PR
From Day 1 up to last dose (Day 57 or 8th Re-initiation dose in escalation phase and up to 2 years for combination phase)
Percentage of stable disease (SD)
Time Frame: From Day 1 up to last dose (Day 57 or 8th Re-initiation dose in escalation phase and up to 2 years for combination phase)
Percentage of participants with SD
From Day 1 up to last dose (Day 57 or 8th Re-initiation dose in escalation phase and up to 2 years for combination phase)
Progression-free survival by Investigator review
Time Frame: From Day 1 to day of last follow-up
Length of time during and after treatment, that a patient lives with disease but it does not get worse
From Day 1 to day of last follow-up
One-year and 2-year OS rates
Time Frame: From Day 1 to Day 730
Percentage of participants from Day 1 of treatment who reach one year or two year survival
From Day 1 to Day 730

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Replimune Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Bristol-Myers Squibb

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Gary Vanasse, MD, Replimune Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 29, 2020

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 25, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 29, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 3, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 27, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 25, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RP3-301

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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