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Study of RP1 Monotherapy and RP1 in Combination With Nivolumab

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ClinicalTrials.gov Identifier: NCT03767348
Recruitment Status : Recruiting
First Posted : December 6, 2018
Last Update Posted : May 22, 2020
Sponsor:
Information provided by (Responsible Party):
Replimune Inc.

Tracking Information
First Submitted Date  ICMJE December 5, 2018
First Posted Date  ICMJE December 6, 2018
Last Update Posted Date May 22, 2020
Actual Study Start Date  ICMJE September 20, 2017
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 27, 2020)
  • Percentage of adverse events (AEs) [ Time Frame: 26 months ]
    Percentage of subjects with adverse events (AEs)
  • Percentage of serious adverse events (SAEs) [ Time Frame: 26 months ]
    Percentage of subjects with serious adverse events (SAEs)
  • Percentage of dose limiting toxicities (DLTs) [ Time Frame: 26 months ]
    Percentage of subjects with dose limiting toxicities (DLTs)
  • Percentage of overall response rate (ORR) [ Time Frame: 26 months ]
    Percentage of overall response rate (ORR) for all participants
  • Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1 [ Time Frame: 20 weeks ]
    Assess the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1 based on the safety and response data collected during Phase 1 Escalation
Original Primary Outcome Measures  ICMJE
 (submitted: December 5, 2018)
  • % subjects with adverse events (AEs) [ Time Frame: 26 months ]
  • % subjects with serious adverse events (AEs) [ Time Frame: 26 months ]
  • % subjects with dose limiting toxicities (DLTs) [ Time Frame: 26 months ]
  • % subjects with overall response (OR) [ Time Frame: 26 months ]
  • Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1 [ Time Frame: 20 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 27, 2020)
  • Percentage of biologic activity [ Time Frame: 20 weeks ]
    Percentage of subjects with biological activity determined by tumor biopsies and biomarker data
  • Percentage subjects with detectable RP1 [ Time Frame: 20 weeks ]
    Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of RP1
  • Percentage of complete response (CR) [ Time Frame: 26 months ]
    Percentage of subjects with a complete response (CR)
  • Median duration of response [ Time Frame: 26 months ]
    Median duration of response of subjects
  • Median progression-free survival [ Time Frame: 26 months ]
    Median duration of progression-free survival of subjects
  • Median overall survival [ Time Frame: 26 months ]
    Median overall survival rate of subjects
Original Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2018)
  • % subjects with biologic activity [ Time Frame: 20 weeks ]
  • % subjects with detectable RP1 [ Time Frame: 20 weeks ]
    Blood, urine, swabs of injection site, dressing, oral mucosa
  • % subjects with complete response [ Time Frame: 26 months ]
  • Median duration of response [ Time Frame: 26 months ]
  • Median progression-free survival [ Time Frame: 26 months ]
  • Median overall survival [ Time Frame: 26 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of RP1 Monotherapy and RP1 in Combination With Nivolumab
Official Title  ICMJE 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
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cancer
  • Melanoma (Skin)
  • Melanoma, Uveal
  • Melanoma, Ocular
  • Bladder Cancer
  • Mismatch Repair Deficiency
  • Microsatellite Instability
  • Non-melanoma Skin Cancer
Intervention  ICMJE
  • Biological: RP1
    Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation
  • Biological: nivolumab
    anti-PD-1 monoclonal antibody
    Other Name: Opdivo
Study Arms  ICMJE
  • Experimental: Dose escalation of RP1 by intratumoral (IT) injection
    Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors
    Intervention: Biological: RP1
  • Experimental: Dose escalation of RP1 by IT injection
    Dose escalation of RP1 alone in 3 cohorts with intratumoral injections in deep/visceral tumors
    Intervention: Biological: RP1
  • Experimental: Dose expansion of RP1 and nivolumab intravenously (IV)
    Doses of RP1 (IT) in superficial tumors with nivolumab (IV)
    Interventions:
    • Biological: RP1
    • Biological: nivolumab
  • Experimental: Dose expansion of RP1 and nivolumab (IV)
    Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)
    Interventions:
    • Biological: RP1
    • Biological: nivolumab
  • Experimental: RP1 (IT) and nivolumab (IV) in melanoma
    Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma
    Interventions:
    • Biological: RP1
    • Biological: nivolumab
  • Experimental: RP1 (IT) and nivolumab (IV) in bladder cancer
    Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with bladder cancer
    Interventions:
    • Biological: RP1
    • Biological: nivolumab
  • Experimental: RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors
    Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with MSI-H or dMMR solid tumors
    Interventions:
    • Biological: RP1
    • Biological: nivolumab
  • Experimental: RP1 (IT) and nivolumab (IV) in NMSC
    Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with NMSC
    Interventions:
    • Biological: RP1
    • Biological: nivolumab
  • Experimental: RP1(IT) and nivo(IV) in anti-PD1 Refractory Cutaneous Melanoma
    Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with cutaneous melanoma who have been previously treated with anti-PD1 therapy for at least 12 weeks and have confirmed disease progression
    Interventions:
    • Biological: RP1
    • Biological: nivolumab
Publications * Thomas S, Kuncheria L, Roulstone V, Kyula JN, Mansfield D, Bommareddy PK, Smith H, Kaufman HL, Harrington KJ, Coffin RS. Development of a new fusion-enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1. J Immunother Cancer. 2019 Aug 10;7(1):214. doi: 10.1186/s40425-019-0682-1.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 27, 2020)
281
Original Estimated Enrollment  ICMJE
 (submitted: December 5, 2018)
168
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
  • At least one measurable and injectable lesion
  • 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
  • Subjects with cutaneous melanoma, that have confirmed progressive disease after at least 12 weeks of anti-PD1 treatment

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gail Iodice 1(857) 701 2235 RPL-001-16@replimune.com
Listed Location Countries  ICMJE United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03767348
Other Study ID Numbers  ICMJE RPL-001-16
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Replimune Inc.
Study Sponsor  ICMJE Replimune Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Selda Samakoglu, MD Replimune Inc.
PRS Account Replimune Inc.
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP