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Study of RP1 Monotherapy and RP1 in Combination With Nivolumab

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 281 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

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
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. 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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.
  • 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

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: Gail Iodice 1(857) 701 2235 RPL-001-16@replimune.com

Locations
Show Show 23 study locations
Sponsors and Collaborators
Replimune Inc.
Investigators
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Study Director: Selda Samakoglu, 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: May 22, 2020
Last Verified: May 2020
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
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