Clinical Trials /

Study of RP2 Monotherapy and RP2 in Combination With Nivolumab in Patients With Solid Tumors

NCT04336241

Description:

RP2-001-18 is a Phase 1, multicenter, open label, single agent dose escalation and combination treatment study of RP2 in adult subjects with advanced solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of RP2 Monotherapy and RP2 in Combination With Nivolumab in Patients With Solid Tumors
  • Official Title: An Open-Label, Multicenter, Phase 1 Study of RP2 as a Single Agent and in Combination With PD1 Blockade in Patients With Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: RP2-001-18
  • NCT ID: NCT04336241

Conditions

  • Cancer

Interventions

DrugSynonymsArms
RP2Dose escalation of RP2 - deep/visceral tumors
nivolumabOpdivoDose expansion of RP2 and nivolumab - deep/visceral tumors

Purpose

RP2-001-18 is a Phase 1, multicenter, open label, single agent dose escalation and combination treatment study of RP2 in adult subjects with advanced solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.

Detailed Description

      RP2 is a genetically modified herpes simplex type 1 virus (HSV-1) that expresses an
      anti-CTLA-4 antibody and is designed to directly destroy tumors and to generate an anti-tumor
      immune response. This is a Phase 1, multicenter, open label, dose escalation and expansion,
      first-in-human (FIH) clinical study to evaluate the safety and tolerability, biodistribution,
      shedding, and preliminary efficacy of RP2 alone and in combination with nivolumab in adult
      subjects with advanced solid tumors.

      The study will be conducted in two parts. The first part of the study is an open-label, dose
      escalation FIH Phase 1 study to assess the safety and tolerability of RP2 and to determine
      the recommended Phase 2 dose (RP2D) to be used in the second part of the study. The second
      part of the study is an open label design to further investigate safety of RP2 in combination
      with nivolumab. It will also assess the biological activity of multiple doses of RP2 in
      combination with nivolumab.
    

Trial Arms

NameTypeDescriptionInterventions
Dose escalation of RP2 - superficial tumorsExperimentalDose escalation of RP2 alone in 3 cohorts with IT injections in superficial tumors.
  • RP2
Dose escalation of RP2 - deep/visceral tumorsExperimentalDose escalation of RP2 alone in 3 cohorts with imaging guided IT injections in deep/visceral tumors.
  • RP2
Dose expansion of RP2 and nivolumab - superficial tumorsExperimentalDoses of RP2 (IT) in superficial tumors with nivolumab (IV).
  • RP2
  • nivolumab
Dose expansion of RP2 and nivolumab - deep/visceral tumorsExperimentalImaging guided doses of RP2 (IT) in deep/visceral tumors.
  • RP2
  • nivolumab
Seronegative cohortExperimentalDoses of RP2 (IT) in HSV seronegative participants.
  • RP2

Eligibility Criteria

        Inclusion Criteria:

          -  Willing and able to participate and comply with all trial requirements and able to
             provide signed and dated informed consent prior to initiation of any trial procedures

          -  Male or Female ≥ 18 years of age

          -  Patients with advanced or metastatic non-neurological solid tumors, who have
             progressed on standard therapy or cannot tolerate standard therapy, or for which there
             is no standard therapy preferred to enrolment in a clinical trial

          -  At least one measurable and injectable tumor of ≥ 1 cm in longest diameter (or shorter
             diameter for lymph nodes).

          -  Women of child-bearing potential (WOCBP) must have a negative urine pregnancy test at
             screening and a negative urine pregnancy test prior to administration of each dose of
             RP2 or nivolumab

          -  WOCBP must agree to use adequate birth control throughout their participation and for
             3 months after RP2 alone and 5 months after nivolumab last study treatment

          -  Males with partners of child-bearing potential must agree to use adequate birth
             control throughout their participation and for 3 months for RP2 alone and 7 months
             after nivolumab last study treatment

          -  Have laboratory values (obtained ≤ 28 days prior to first infusion day) in accordance
             with the study protocol

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1

        Combination patients only:

          -  Baseline ECG that does not show abnormalities according to the protocol

          -  Baseline troponin < 0.06 ng/mL

          -  Baseline oxygen saturation levels that do not show abnormalities according to the
             protocol

        Exclusion Criteria:

          -  Prior treatment with an oncolytic therapy

          -  History of viral infections according to the protocol

          -  Systemic infection requiring IV antibiotics within 14 days prior to dosing

          -  Prior complications with herpes infections

          -  Chronic use of anti-virals

          -  Systemic therapies for cancer within 4 weeks of first dose (some others may be
             accepted with shorter time periods)

          -  Conditions that require certain doses of steroids (some doses and types will be
             permitted)

          -  Known active brain metastases - previously treated brain metastases may be permitted

          -  Major surgery ≤ 2 weeks prior to starting study drug

          -  Prior malignancy active with the previous 3 years; except for locally curable cancers
             that have apparently been cured

          -  Female who has a positive urine pregnancy test or is breast-feeding or planning to
             become pregnant during study treatment and 90 days for RP2 alone or 5 months for RP2
             and nivolumab after the last dose of treatment

          -  Participation in another clinical study within 4 weeks prior to the first dose

        Combination patients only:

          -  Participants with history of life-threatening toxicity related to prior immune therapy
             except those that are likely to re-occur with standard countermeasures

          -  Treatment with botanical preparations within 2 weeks prior to treatment

          -  Certain autoimmune diseases, some types will be permitted

          -  Allergy or sensitivity to study drug components

          -  History of interstitial lung disease

          -  Severe hypersensitivity to another monoclonal antibody

          -  Has received radiotherapy within 2 weeks of start of study treatment

          -  Has received a live vaccine within 30 days prior to first dose of study drug

          -  History of non-infectious pneumonitis

          -  History or current evidence of any condition, therapy, or laboratory abnormality that
             might confound the results of the study

          -  Other serious or uncontrolled medical disorders

          -  Known psychiatric or substance abuse disorders that would interfere with cooperating
             with the requirements of the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of adverse events (AEs)
Time Frame:From Day 1 up to 60 days after last dose
Safety Issue:
Description:Percentage of subjects with AEs

Secondary Outcome Measures

Measure:Percentage of biologic activity
Time Frame:20 weeks
Safety Issue:
Description:Percentage of subjects with biological activity determined by tumor biopsies and biomarker data
Measure:Percentage of subjects with detectable RP2
Time Frame:20 weeks
Safety Issue:
Description:Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of RP2.
Measure:Change in HSV-1 antibody levels
Time Frame:From Day 1 up to last dose (up to 4 months for dose escalation phase and up to 5.5 months for expansion phase)).
Safety Issue:
Description:Change in HSV-1 antibody levels during treatment compared to baseline
Measure:Percentage of overall response rate (ORR)
Time Frame:3 years
Safety Issue:
Description:Percentage of ORR.
Measure:Median duration of response
Time Frame:3 years
Safety Issue:
Description:Median duration of response of subjects
Measure:Median progression-free survival
Time Frame:3 years
Safety Issue:
Description:Median duration of progression-free survival of subjects
Measure:Median overall survival
Time Frame:3 years
Safety Issue:
Description:Median overall survival rate of subjects
Measure:Percentage of complete response (CR)
Time Frame:From Day 1 up to last dose (up to 8 weeks for escalation phase and up to 2 years for expansion phase).
Safety Issue:
Description:Percentage of subjects with a CR
Measure:Percentage of partial response (PR)
Time Frame:From Day 1 up to last dose (up to 8 weeks for escalation phase and up to 2 years for expansion phase).
Safety Issue:
Description:Percentage of subjects with a PR
Measure:Percentage of stable disease (SD)
Time Frame:From Day 1 up to last dose (up to 8 weeks for escalation phase and up to 2 years for expansion phase).
Safety Issue:
Description:Percentage of subjects with SD

Details

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

Last Updated

April 3, 2020