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

NCT04735978 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: RP3-301
• Study Type: interventional
• Target: 123
• Locations: 5 countries
• Sites: 13

Brief 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.

Conditions

Advanced Solid Tumor

Keywords

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

Outcome Measures

Primary Outcomes (6)

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

  Percentage of participants with DLTs

  From Day 1 up to 30 days after last dose

• Incidence and severity of treatment emergent adverse events (TEAEs)

  Percentage of participants with TEAEs

  From Day 1 up to 60 days after last dose

• Incidence and severity of serious adverse events (SAEs)

  Percentage of participants with SAEs

  From Day 1 up to 60 days after last dose

• Incidence of TEAEs ≥ Grade 3

  Percentage of participants with TEAEs ≥ Grade 3

  From Day 1 up to 60 days after last dose

• Percentage of events requiring withdrawal

  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

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

  7 months

Secondary Outcomes (12)

• Percentage of biologic activity

  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

  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.

  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

  From Day 1 to Day 43

• 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

Study Arms (3)

Dose escalation of RP3 - superficial and/or deep/visceral tumors

EXPERIMENTAL

Dose escalation of RP3 alone in 2 cohorts with intratumoral (IT) injections including use of imaging guided injection for deep tumors.

Biological: RP3

Dose combination of RP3 and anti-PD1 therapy - superficial and/or deep/visceral tumors

EXPERIMENTAL

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

Seronegative cohort

EXPERIMENTAL

Doses of RP3 (IT) in HSV seronegative participants.

Biological: RP3

Interventions

RP3 BIOLOGICAL

Genetically modified HSV-1

Dose combination of RP3 and anti-PD1 therapy - superficial and/or deep/visceral tumors; Dose escalation of RP3 - superficial and/or deep/visceral tumors; Seronegative cohort

Nivolumab BIOLOGICAL

anti-PD1 monoclonal antibody

Dose combination of RP3 and anti-PD1 therapy - superficial and/or deep/visceral tumors

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

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

Study Sites (13)

University of Iowa

Iowa City, Iowa, 52242, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Laboratoire de Recherche Translationnelle en Immunotherapie (LRTI), Gustave Roussy

Villejuif, 94805, France

Location

University of Athens

Athens, 11527, Greece

Location

University General Hospital Attikon

Athens, 12462, Greece

Location

Vall d'Hebron Hospital Hospital Universitario Vall d´Hebron (Vall d'Hebron University Hospital)

Barcelona, 08035, Spain

Location

Hospital Clinic Barcelona

Barcelona, 08036, Spain

Location

START Madrid CIO Clara Campal, Hospital Universitario HM Sanchinarro Unidad de Ensayos Fase I Panta 3

Madrid, 28050, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Merseyside, CH63 4JY, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

Churchill Hospital

Oxford, OX3 9DU, United Kingdom

Location

MeSH Terms

Interventions

Nivolumab

Intervention Hierarchy (Ancestors)

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

Study Officials

• Gary Vanasse, MD

  Replimune Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 - Dose Escalation - Participants will be enrolled into two sequential dose level cohorts. * Cohort 1: 1 × 105 plaque-forming units (PFU)/mL on Day 1 followed by 1 × 106 PFU/mL every 2 weeks (Q2W) for up to 5 doses. * Cohort 2: 1 × 106 PFU/mL on Day 1 followed by 1 × 107 PFU/mL Q2W for up to 5 doses. Part 2 - Dose Combination - Patients will be enrolled into 1 of 5 dose-expansion cohorts. Expansion Cohorts 1, 2, and 4 will enroll patients with head and neck cancer, lung cancer, breast cancer, or GI cancer. Expansion Cohort 3 will enroll patients with any solid organ malignancy who have at least 2 tumors that can be injected and biopsied. Expansion Cohort 5 will enroll patients with melanoma. * Expansion Cohort 1 (RP3 + Nivolumab) * Expansion Cohort 2 (RP3 Followed by Nivolumab) * Expansion Cohort 3 (RP3 Monotherapy Translational Cohort) * Expansion Cohort 4 (RP3 Monotherapy) * Expansion Cohort 5 (RP3 + Nivolumab in Melanoma)

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: February 3, 2021
• Study Start: December 29, 2020
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

FR (1); US (3); GB (3); GR (2); ES (4)