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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 : December 6, 2018
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) Melanoma, Uveal Melanoma, Ocular Bladder Cancer Mismatch Repair Deficiency Microsatellite Instability Non-melanoma Skin Cancer Biological: RP1 Biological: nivolumab Phase 1 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.

Study Type : Interventional
Estimated Enrollment : 168 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 2021
Estimated Study Completion Date : December 2021


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

Experimental: Dose escalation of RP1 by IT injection
Dose escalation of RP1 alone in 3 cohorts with intratumoral injections in deep/visceral tumors
Biological: RP1
Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation

Experimental: Dose expansion of RP1 and nivolumab intravenously (IV)
Doses of RP1 (IT) in superficial tumors with nivolumab (IV)
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

Experimental: Dose expansion of RP1 and nivolumab (IV)
Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)
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

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 for tumor lysis and immune stimulation

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

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
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

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 for tumor lysis and immune stimulation

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 NMSC
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




Primary Outcome Measures :
  1. % subjects with adverse events (AEs) [ Time Frame: 26 months ]
  2. % subjects with serious adverse events (AEs) [ Time Frame: 26 months ]
  3. % subjects with dose limiting toxicities (DLTs) [ Time Frame: 26 months ]
  4. % subjects with overall response (OR) [ Time Frame: 26 months ]
  5. Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1 [ Time Frame: 20 weeks ]

Secondary Outcome Measures :
  1. % subjects with biologic activity [ Time Frame: 20 weeks ]
  2. % subjects with detectable RP1 [ Time Frame: 20 weeks ]
    Blood, urine, swabs of injection site, dressing, oral mucosa

  3. % subjects with complete response [ Time Frame: 26 months ]
  4. median duration of response [ Time Frame: 26 months ]
  5. median progression free survival [ Time Frame: 26 months ]
  6. median overall survival [ Time Frame: 26 months ]


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:

  • 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

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
Contact: Alexandra Budden +1 781 995 2449 RPL00116@replimune.com
Contact: Alex Deterding +44 (0)7990 041 930 RPL00116@replimune.com

Locations
United Kingdom
Oxford University Hospitals NHS Trust Recruiting
Oxford, Oxfordshire, United Kingdom
Principal Investigator: Mark R Middleton, MD, PhD, FRCP         
Royal Marsden Hospital Recruiting
London, United Kingdom
Principal Investigator: Kevin Harrington, BSc FRCP PhD         
Sponsors and Collaborators
Replimune Inc.
Investigators
Study Director: Howard Kaufman, MD Replimune Inc.

Responsible Party: Replimune Inc.
ClinicalTrials.gov Identifier: NCT03767348     History of Changes
Other Study ID Numbers: RPL-001-16
First Posted: December 6, 2018    Key Record Dates
Last Update Posted: December 6, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Melanoma
Urinary Bladder Neoplasms
Skin Neoplasms
Microsatellite Instability
Brain Neoplasms
Neoplastic Syndromes, Hereditary
Colorectal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Skin Diseases
Genomic Instability
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Intestinal Neoplasms
Gastrointestinal Neoplasms