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Study of RP1 Monotherapy and RP1 in Combination With Nivolumab (IGNYTE)

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ClinicalTrials.gov Identifier: NCT03767348
Recruitment Status : Recruiting
First Posted : December 6, 2018
Last Update Posted : July 29, 2021
Sponsor:
Information provided by (Responsible Party):
Replimune Inc.

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.

Condition or disease Intervention/treatment Phase
Cancer Melanoma (Skin) Mismatch Repair Deficiency Microsatellite Instability Non-melanoma Skin Cancer Cutaneous Melanoma NSCLC Biological: RP1 Biological: nivolumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 20, 2017
Estimated Primary Completion Date : November 2024
Estimated Study Completion Date : November 2024


Arm Intervention/treatment
Experimental: Dose escalation of RP1 by intratumoral (IT) injection in superficial tumors
Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors
Biological: RP1
Genetically modified herpes simplex type 1 virus

Experimental: Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors
Dose escalation of RP1 alone in 3 cohorts with IT injections in deep/visceral tumors
Biological: RP1
Genetically modified herpes simplex type 1 virus

Experimental: Dose expansion of RP1 and nivolumab (IV) in superficial tumors
Doses of RP1 (IT) in superficial tumors with nivolumab (IV)
Biological: RP1
Genetically modified herpes simplex type 1 virus

Biological: nivolumab
anti-PD-1 monoclonal antibody
Other Name: Opdivo

Experimental: Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors
Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)
Biological: RP1
Genetically modified herpes simplex type 1 virus

Biological: nivolumab
anti-PD-1 monoclonal antibody
Other Name: Opdivo

Experimental: RP1 (IT) and nivolumab (IV) in melanoma
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma
Biological: RP1
Genetically modified herpes simplex type 1 virus

Biological: nivolumab
anti-PD-1 monoclonal antibody
Other Name: Opdivo

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
Biological: RP1
Genetically modified herpes simplex type 1 virus

Biological: nivolumab
anti-PD-1 monoclonal antibody
Other Name: Opdivo

Experimental: RP1 (IT) and nivolumab (IV) in NMSC
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer
Biological: RP1
Genetically modified herpes simplex type 1 virus

Biological: nivolumab
anti-PD-1 monoclonal antibody
Other Name: Opdivo

Experimental: RP1(IT) and nivolumab (IV) in anti-PD1 Failed 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
Biological: RP1
Genetically modified herpes simplex type 1 virus

Biological: nivolumab
anti-PD-1 monoclonal antibody
Other Name: Opdivo

Experimental: RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer who have been previously treated with anti-PD1/PD-L1 therapy
Biological: RP1
Genetically modified herpes simplex type 1 virus

Biological: nivolumab
anti-PD-1 monoclonal antibody
Other Name: Opdivo

Experimental: RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non small cell lung cancer who have been previously treated with anti-PD1/PD-L1 therapy
Biological: RP1
Genetically modified herpes simplex type 1 virus

Biological: nivolumab
anti-PD-1 monoclonal antibody
Other Name: Opdivo




Primary Outcome Measures :
  1. Percentage of adverse events (AEs) [ Time Frame: 26 months ]
    Percentage of subjects with adverse events (AEs)

  2. Percentage of serious adverse events (SAEs) [ Time Frame: 26 months ]
    Percentage of subjects with serious adverse events (SAEs)

  3. Percentage of dose limiting toxicities (DLTs) [ Time Frame: 26 months ]
    Percentage of subjects with dose limiting toxicities (DLTs)

  4. Percentage of overall response rate (ORR) [ Time Frame: 26 months ]
    Percentage of overall response rate (ORR) for all participants

  5. 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


Secondary Outcome Measures :
  1. Percentage of biologic activity [ Time Frame: 20 weeks ]
    Percentage of subjects with biological activity determined by tumor biopsies and biomarker data

  2. 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

  3. Percentage of complete response (CR) [ Time Frame: 26 months ]
    Percentage of subjects with a complete response (CR)

  4. Median duration of response [ Time Frame: 26 months ]
    Median duration of response of subjects

  5. Median progression-free survival [ Time Frame: 26 months ]
    Median duration of progression-free survival of subjects

  6. Median overall survival [ Time Frame: 26 months ]
    Median overall survival rate of subjects



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
  • At least one measurable and injectable lesion
  • Have provided a former tumor pathology specimen or be willing to supply a new tumor sample from a biopsy
  • Have a predicted life expectancy of ≥ 3 months
  • Measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
  • Subjects with MSI-H or dMMR tumors: has diagnosis of MSI-H or metatstatic 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
  • Subjects 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-PD1/PD-L1 therapy is indicated, or have refused, become intolerant to or have no further therapy options available
  • Subjects with anti-PD1 failed cutaneous melanoma: has confirmed progressive disease while on anti-PD1 treatment for at least 8 weeks and documented BRAF mutation status
  • Subjects with anti-PD1 failed NSCLC: has confirmed progressive disease after no more than two prior systemic treatments including anti-PD1/PD-L1 treatment

Exclusion Criteria:

  • Prior treatment with an oncolytic therapy
  • History of viral infections according to the protocol
  • Prior complications with herpes infections
  • Chronic use of anti-virals
  • Uncontrolled/untreated brain metastasis
  • History of interstitial lung disease
  • History of non-infectious pneumonitis
  • History of clinically significant cardiovascular disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03767348


Contacts
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Contact: Clinical Trials at Replimune 1-781-222-9570 Clinicaltrials@replimune.com

Locations
Show Show 28 study locations
Sponsors and Collaborators
Replimune Inc.
Investigators
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Study Director: Jeannie Hou, MD Replimune Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Replimune Inc.
ClinicalTrials.gov Identifier: NCT03767348    
Other Study ID Numbers: RPL-001-16
First Posted: December 6, 2018    Key Record Dates
Last Update Posted: July 29, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Replimune Inc.:
Oncolytic virus
Oncolytic Immuno-gene therapy
Non-melanoma Skin Cancer
Cutaneous Melanoma
Anti-PD1 failed
Melanoma (skin)
Additional relevant MeSH terms:
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Melanoma
Skin Neoplasms
Microsatellite Instability
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms by Site
Skin Diseases
Genomic Instability
Pathologic Processes
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action