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Active, not recruitingNCT04735978Updated Feb 27, 2026

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

A Phase 1 interventional study of RP3 and Nivolumab in Advanced Solid Tumor, sponsored by Replimune, Inc.. Active, not recruiting at 13 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-02-27.

Sponsored by Replimune, Inc. · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
123
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
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Study summary

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.

Read the 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

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Conditions studied

  • Advanced Solid Tumor

Keywords

  • Advanced solid tumors
  • Immunotherapy
  • Immuno-oncology
  • Oncolytic virus
  • Oncolytic immuno-gene therapy
03

In context

Lead sponsor

Replimune, Inc. is the lead sponsor of 10 studies on the registry; 4 are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
123 participants (estimated)

Study arms

  • 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

  • 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 · Biological: Nivolumab

  • Experimental
    Seronegative cohort

    Doses of RP3 (IT) in HSV seronegative participants.

    Biological: RP3

Interventions

  • BiologicalRP3

    Genetically modified HSV-1

  • BiologicalNivolumab

    anti-PD1 monoclonal antibody

06

What researchers measure

Primary outcomes

  1. Incidence of dose limiting toxicities (DLTs) during the DLT period

    Percentage of participants with DLTs

    Time frame: From Day 1 up to 30 days after last dose

  2. Incidence and severity of treatment emergent adverse events (TEAEs)

    Percentage of participants with TEAEs

    Time frame: From Day 1 up to 60 days after last dose

  3. Incidence and severity of serious adverse events (SAEs)

    Percentage of participants with SAEs

    Time frame: From Day 1 up to 60 days after last dose

  4. Incidence of TEAEs ≥ Grade 3

    Percentage of participants with TEAEs ≥ Grade 3

    Time frame: From Day 1 up to 60 days after last dose

  5. Percentage of events requiring withdrawal

    Percentage of participants experiencing events requiring withdrawal from treatment.

    Time frame: From Day 1 up to last dose (up to 8 weeks in escalation phase and up to 2 years in combination phase)

  6. Recommended phase 2 dose (RP2D) of RP3

    RP2D of RP3 based on the safety and response data collected during the dose escalation phase (Part 1)

    Time frame: 7 months

Secondary outcomes

  1. Percentage of biologic activity

    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).

    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

  2. Incidence of clearance of RP3 from blood and urine

    Incidence of clearance of RP3 from blood and urine before and after each injection

    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

  3. Percentage of participants with detectable RP3.

    Data gathered from blood, urine, swabs of injection site, dressing and oral mucosa to determine the shedding and biodistribution of 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

  4. Change in HSV-1 antibody levels

    Change in HSV-1 antibody levels during treatment compared to baseline

    Time frame: From Day 1 to Day 43

  5. Percentage of HSV-1 seronegative patients with TEAEs

    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

  6. Percentage of objective overall response rate (ORR)

    Percentage of ORR

    Time frame: Up to 3 years since first patient in

  7. Median duration of response

    Median duration of response of participants

    Time frame: Up to 3 years since first patient in

  8. Percentage of complete response (CR)

    Percentage of participants with a 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)

  9. Percentage of partial response (PR)

    Percentage of participants with a 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)

  10. Percentage of stable disease (SD)

    Percentage of participants with 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)

  11. Progression-free survival by Investigator review

    Length of time during and after treatment, that a patient lives with disease but it does not get worse

    Time frame: From Day 1 to day of last follow-up

  12. One-year and 2-year OS rates

    Percentage of participants from Day 1 of treatment who reach one year or two year survival

    Time frame: From Day 1 to Day 730

07

Study locations

13 sites
  • University of Iowa
    Iowa City, Iowa 52242, United States
  • UPMC Hillman Cancer Center
    Pittsburgh, Pennsylvania 15232, United States
  • MD Anderson Cancer Center
    Houston, Texas 77030, United States
  • Laboratoire de Recherche Translationnelle en Immunotherapie (LRTI), Gustave Roussy
    Villejuif, 94805, France
  • University of Athens
    Athens, 11527, Greece
  • University General Hospital Attikon
    Athens, 12462, Greece
  • Vall d'Hebron Hospital Hospital Universitario Vall d´Hebron (Vall d'Hebron University Hospital)
    Barcelona, 08035, Spain
  • Hospital Clinic Barcelona
    Barcelona, 08036, Spain
  • START Madrid CIO Clara Campal, Hospital Universitario HM Sanchinarro Unidad de Ensayos Fase I Panta 3
    Madrid, 28050, Spain
  • Hospital Clinico Universitario de Valencia
    Valencia, 46010, Spain
  • The Clatterbridge Cancer Centre NHS Foundation Trust
    Bebington, Merseyside CH63 4JY, United Kingdom
  • The Royal Marsden NHS Foundation Trust
    London, SW3 6JJ, United Kingdom
  • Churchill Hospital
    Oxford, OX3 9DU, United Kingdom
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 27, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT04735978
Lead sponsor
Replimune, Inc.
Collaborators
Bristol-Myers Squibb
Responsible party
Sponsor
First posted
Feb 3, 2021
Start date
Dec 29, 2020
Primary completion
Nov 30, 2026 (estimated)
Completion
Nov 30, 2026 (estimated)
Last update
Feb 27, 2026

Study contacts

Gary Vanasse, MD
study director · Replimune, Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Feb 2026. You cannot join it, but the record below documents what was studied.

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