Clinical Trials /

Study of RP3 Monotherapy and RP3 in Combination With Anti-PD1 Therapy in Patients With Solid Tumours

NCT04735978

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of RP3 Monotherapy and RP3 in Combination With Anti-PD1 Therapy in Patients With Solid Tumours
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: RP3-301
  • NCT ID: NCT04735978

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
RP3Dose combination of RP3 and anti-PD1 therapy - superficial and/or deep/visceral tumors
anti-PD1 monoclonal antibodyDose combination of RP3 and anti-PD1 therapy - superficial and/or deep/visceral tumors

Purpose

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.

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
    

Trial Arms

NameTypeDescriptionInterventions
Dose escalation of RP3 - superficial and/or deep/visceral tumorsExperimentalDose escalation of RP3 alone in 2 cohorts with intratumoral (IT) injections including use of imaging guided injection for deep tumors.
  • RP3
Dose combination of RP3 and anti-PD1 therapy - superficial and/or deep/visceral tumorsExperimentalDose combination of RP3 and anti-PD1 therapy. IT injections of RP3 including use of imaging guided injection for deep tumors.
  • RP3
  • anti-PD1 monoclonal antibody
Seronegative cohortExperimentalDoses of RP3 (IT) in HSV seronegative participants.
  • RP3

Eligibility Criteria

        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

        Exclusion Criteria:

          -  Prior treatment with an oncolytic 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

          -  History of interstitial lung disease

          -  Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities (DLTs) during the DLT period
Time Frame:From Day 1 up to 30 days after last dose
Safety Issue:
Description:Percentage of participants with DLTs

Secondary Outcome Measures

Measure:Percentage of biologic activity
Time Frame:From Day 1 to 12 months following the last dose in dose escalation. From Day 1 to 100 days following the last dose in dose combination
Safety Issue:
Description: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).
Measure: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
Safety Issue:
Description:Incidence of clearance of RP3 from blood and urine before and after each injection
Measure: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
Safety Issue:
Description:Data gathered from blood, urine, swabs of injection site, dressing and oral mucosa to determine the shedding and biodistribution of RP3
Measure:Change in HSV-1 antibody levels
Time Frame:From Day 1 to Day 43
Safety Issue:
Description:Change in HSV-1 antibody levels during treatment compared to baseline
Measure: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
Safety Issue:
Description:Percentage of HSV-1 seronegative patients with TEAEs
Measure:Percentage of objective overall response rate (ORR)
Time Frame:Up to 3 years since first patient in
Safety Issue:
Description:Percentage of ORR
Measure:Median duration of response
Time Frame:Up to 3 years since first patient in
Safety Issue:
Description:Median duration of response of participants
Measure: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)
Safety Issue:
Description:Percentage of participants with a CR
Measure: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)
Safety Issue:
Description:Percentage of participants with a PR
Measure: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)
Safety Issue:
Description:Percentage of participants with SD

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Replimune Inc.

Trial Keywords

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

Last Updated

May 7, 2021