Clinical Trials /

Study of RP1 Monotherapy and RP1 in Combination With Nivolumab

NCT03767348

Description:

RPL-001-16 is a Phase 1/2, open label, dose escalation and expansion clinical study of RP1 alone and in combination with nivolumab in adult subjects with advanced and/or refractory solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.

Related Conditions:
  • Bladder Carcinoma
  • Malignant Solid Tumor
  • Melanoma
  • Skin Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of RP1 Monotherapy and RP1 in Combination With Nivolumab
  • Official Title: An Open-Label, Multicenter, Phase 1/2 Study of RP1 as a Single Agent and in Combination With PD1 Blockade in Patients With Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: RPL-001-16
  • NCT ID: NCT03767348

Conditions

  • Cancer
  • Melanoma (Skin)
  • Melanoma, Uveal
  • Melanoma, Ocular
  • Bladder Cancer
  • Mismatch Repair Deficiency
  • Microsatellite Instability
  • Non-melanoma Skin Cancer

Interventions

DrugSynonymsArms
RP1Dose escalation of RP1 by intratumoral (IT) injection
nivolumabOpdivoDose expansion of RP1 and nivolumab intravenously (IV)

Purpose

RPL-001-16 is a Phase 1/2, open label, dose escalation and expansion clinical study of RP1 alone and in combination with nivolumab in adult subjects with advanced and/or refractory solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.

Detailed Description

      RP1 is a genetically modified herpes simplex type 1 virus that is designed to directly
      destroy tumors and to generate an anti-tumor immune response. This is a Phase 1/2, open
      label, multicenter, dose escalation and expansion, first-in-human (FIH) clinical study to
      evaluate the safety and tolerability, biodistribution, shedding, and preliminary efficacy of
      RP1 alone and in combination with nivolumab in adult subjects with advanced and/or refractory
      solid tumors. The study will include a dose escalation phase for single agent RP1, an
      expansion phase with a combination of RP1 and nivolumab and a Phase 2 portion in specified
      tumor types for the combination therapy.
    

Trial Arms

NameTypeDescriptionInterventions
Dose escalation of RP1 by intratumoral (IT) injectionExperimentalDose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors
  • RP1
Dose escalation of RP1 by IT injectionExperimentalDose escalation of RP1 alone in 3 cohorts with intratumoral injections in deep/visceral tumors
  • RP1
Dose expansion of RP1 and nivolumab intravenously (IV)ExperimentalDoses of RP1 (IT) in superficial tumors with nivolumab (IV)
  • RP1
  • nivolumab
Dose expansion of RP1 and nivolumab (IV)ExperimentalDoses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)
  • RP1
  • nivolumab
RP1 (IT) and nivolumab (IV) in melanomaExperimentalDoses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma
  • RP1
  • nivolumab
RP1 (IT) and nivolumab (IV) in bladder cancerExperimentalDoses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with bladder cancer
  • RP1
  • nivolumab
RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumorsExperimentalDoses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with MSI-H or dMMR solid tumors
  • RP1
  • nivolumab
RP1 (IT) and nivolumab (IV) in NMSCExperimentalDoses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with NMSC
  • RP1
  • nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Must be 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

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

          -  Have at least one injectable tumor

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

          -  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
             RP1 or nivolumab

          -  WOCBP must agree to use adequate birth control throughout their participation and for
             3 months after RP1 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 RP1 alone and 7 months
             after nivolumab last study treatment

        For Subjects in the Combination Treatment

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

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

          -  Have provided a former tumor pathology specimen or be willing to supply a new tumor
             sample from a biopsy

        For Subjects in Phase 2 only

          -  Have a predicted life expectancy of ≥ 3 months

          -  Evaluable or measurable disease, according to Response Evaluation Criteria in Solid
             Tumors (RECIST) v1.1 criteria,

          -  Subjects with melanoma: has Stage IIIb to IV (skin, eye or mucosal) for whom anti PD-1
             therapy is indicated or who have previously received an anti-PD-1 therapy, or have
             refused, become intolerant to or have no further therapy options available

          -  Subjects with MSI-H tumors: has diagnosis of MSI-H tumor (according to protocol
             definition) for whom anti PD-1 therapy is indicated, or have refused, become
             intolerant to or have no further therapy options available

          -  Subject with dMMR tumors: has diagnosis of dMMR tumor (according to protocol
             definition) for whom anti PD-1 therapy is indicated, or have refused, become
             intolerant to or have no further therapy options available

          -  Subject with NMSC: has diagnosis of locally advanced or metastatic NMSC that are not
             considered treatable by surgery including basal cell carcinoma, cutaneous squamous
             cell carcinoma, basosquamous carcinoma, Merkel cell carcinoma and other non-melanoma
             skin cancers (per protocol) for whom anti PD-1 therapy is indicated, or have refused,
             become intolerant to or have no further therapy options available Subjects with
             bladder cancer: diagnosis of locally advanced or metastatic bladder cancer for whom
             anti PD-1 therapy is indicated, or have refused, become intolerant to or have no
             further therapy options available

        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

          -  Prior certain other diagnosis of cancer

          -  Is participating in another clinical study or has participated in the past 4 weeks
             prior to the first dose

        Combination Phase Subjects

          -  Certain autoimmune diseases, some types will be permitted

          -  Allergy or sensitivity to study drug components

          -  History of interstitial lung disease

          -  History of non-infectious pnuemonitis

          -  Other serious or uncontrolled medical disorders
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:% subjects with adverse events (AEs)
Time Frame:26 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:% subjects with biologic activity
Time Frame:20 weeks
Safety Issue:
Description:
Measure:% subjects with detectable RP1
Time Frame:20 weeks
Safety Issue:
Description:Blood, urine, swabs of injection site, dressing, oral mucosa
Measure:% subjects with complete response
Time Frame:26 months
Safety Issue:
Description:
Measure:median duration of response
Time Frame:26 months
Safety Issue:
Description:
Measure:median progression free survival
Time Frame:26 months
Safety Issue:
Description:
Measure:median overall survival
Time Frame:26 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Replimune Inc.

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