Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of RP2 Monotherapy and RP2 in Combination With Nivolumab in Patients With Solid Tumors

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: NCT04336241
Recruitment Status : Recruiting
First Posted : April 7, 2020
Last Update Posted : May 7, 2021
Sponsor:
Information provided by (Responsible Party):
Replimune Inc.

Brief Summary:
RP2-001-18 is a Phase 1, multicenter, open label, single agent dose escalation and combination treatment study of RP2 in adult subjects with advanced 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 Biological: RP2 Biological: nivolumab Phase 1

Detailed Description:

RP2 is a genetically modified herpes simplex type 1 virus (HSV-1) that expresses an anti-CTLA-4 antibody and is designed to directly destroy tumors and to generate an anti-tumor immune response. This is a Phase 1, multicenter, open label, dose escalation and expansion, first-in-human (FIH) clinical study to evaluate the safety and tolerability, biodistribution, shedding, and preliminary efficacy of RP2 alone and in combination with nivolumab in adult subjects with advanced solid tumors.

The study will be conducted in two parts. The first part of the study is an open-label, dose escalation FIH Phase 1 study to assess the safety and tolerability of RP2 and to determine the recommended Phase 2 dose (RP2D) to be used in the second part of the study. The second part of the study is an open label design to further investigate safety of RP2 in combination with nivolumab. It will also assess the biological activity of multiple doses of RP2 in combination with nivolumab.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Part 1 - Dose Escalation - Patients will be enrolled into three sequential dose level cohorts.

Part 2 - Dose expansion - Patients will receive a fixed dose of RP2 in combination with Nivolumab.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Phase 1 Study of RP2 as a Single Agent and in Combination With PD1 Blockade in Patients With Solid Tumors
Actual Study Start Date : October 17, 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Dose escalation of RP2 - superficial tumors
Dose escalation of RP2 alone in 3 cohorts with IT injections in superficial tumors.
Biological: RP2
Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation

Experimental: Dose escalation of RP2 - deep/visceral tumors
Dose escalation of RP2 alone in 3 cohorts with imaging guided IT injections in deep/visceral tumors.
Biological: RP2
Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation

Experimental: Dose expansion of RP2 and nivolumab - superficial tumors
Doses of RP2 (IT) in superficial tumors with nivolumab (IV).
Biological: RP2
Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation

Biological: nivolumab
Programmed death receptor (PD-1) blocking antibody
Other Name: Opdivo

Experimental: Dose expansion of RP2 and nivolumab - deep/visceral tumors
Imaging guided doses of RP2 (IT) in deep/visceral tumors.
Biological: RP2
Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation

Biological: nivolumab
Programmed death receptor (PD-1) blocking antibody
Other Name: Opdivo

Experimental: Seronegative cohort
Doses of RP2 (IT) in HSV seronegative participants.
Biological: RP2
Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation




Primary Outcome Measures :
  1. Percentage of adverse events (AEs) [ Time Frame: From Day 1 up to 60 days after last dose ]
    Percentage of subjects with AEs

  2. Percentage of serious adverse events (SAEs) [ Time Frame: From Day 1 up to 60 days after last dose ]
    Percentage of subjects with SAEs

  3. Percentage of dose limiting toxicities (DLTs) [ Time Frame: From Day 1 up to 30 days after last dose. ]
    Percentage of subjects with DLTs

  4. Percentage of treatment emergent adverse events (TEAEs) [ Time Frame: From Day 1 up to 60 days after last dose. ]
    Percentage of subjects with TEAEs

  5. Percentage of TEAEs ≥ Grade 3 [ Time Frame: From Day 1 up to 60 days after last dose. ]
    Percentage of subjects with TEAEs ≥ Grade 3

  6. Percentage of events requiring withdrawal [ Time Frame: From Day 1 up to last dose (up to 8 weeks for dose escalation phase and up to 2 years for expansion phase)). ]
    Percentage of subjects experiencing events requiring withdrawal from treatment.

  7. Maximum tolerated dose (MTD) of RP2 [ Time Frame: 7 months ]
    MTD on the safety and response data collected during the dose escalation phase (Part 1).

  8. Recommended Phase 2 dose (RP2D) of RP2 [ Time Frame: 7 months ]
    RP2D of RP2 based on the safety and response data collected during the dose escalation phase (Part 1).


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 of subjects with detectable RP2 [ Time Frame: 20 weeks ]
    Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of RP2.

  3. Change in HSV-1 antibody levels [ Time Frame: From Day 1 up to last dose (up to 4 months for dose escalation phase and up to 5.5 months for expansion phase)). ]
    Change in HSV-1 antibody levels during treatment compared to baseline

  4. Percentage of overall response rate (ORR) [ Time Frame: 3 years ]
    Percentage of ORR.

  5. Median duration of response [ Time Frame: 3 years ]
    Median duration of response of subjects

  6. Median progression-free survival [ Time Frame: 3 years ]
    Median duration of progression-free survival of subjects

  7. Median overall survival [ Time Frame: 3 years ]
    Median overall survival rate of subjects

  8. Percentage of complete response (CR) [ Time Frame: From Day 1 up to last dose (up to 8 weeks for escalation phase and up to 2 years for expansion phase). ]
    Percentage of subjects with a CR

  9. Percentage of partial response (PR) [ Time Frame: From Day 1 up to last dose (up to 8 weeks for escalation phase and up to 2 years for expansion phase). ]
    Percentage of subjects with a PR

  10. Percentage of stable disease (SD) [ Time Frame: From Day 1 up to last dose (up to 8 weeks for escalation phase and up to 2 years for expansion phase). ]
    Percentage of subjects with SD



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.


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

Inclusion Criteria:

  • 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
  • Patients with advanced or metastatic non-neurological solid tumors, who have progressed on standard therapy or cannot tolerate standard therapy, or for which there is no standard therapy preferred to enrolment in a clinical trial
  • At least one measurable and injectable tumor of ≥ 1 cm in longest diameter (or shorter diameter for lymph nodes).
  • 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 RP2 or nivolumab
  • WOCBP must agree to use adequate birth control throughout their participation and for 3 months after RP2 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 RP2 alone and 7 months after nivolumab last study treatment
  • Have laboratory values (obtained ≤ 28 days prior to first infusion day) in accordance with the study protocol
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1

Combination patients only:

  • Baseline ECG that does not show abnormalities according to the protocol
  • Baseline troponin < 0.06 ng/mL
  • Baseline oxygen saturation levels that do not show abnormalities according to the protocol

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
  • Major surgery ≤ 2 weeks prior to starting study drug
  • Prior malignancy active with the previous 3 years; except for locally curable cancers that have apparently been cured
  • Female who has a positive urine pregnancy test or is breast-feeding or planning to become pregnant during study treatment and 90 days for RP2 alone or 5 months for RP2 and nivolumab after the last dose of treatment
  • Participation in another clinical study within 4 weeks prior to the first dose

Combination patients only:

  • Participants with history of life-threatening toxicity related to prior immune therapy except those that are likely to re-occur with standard countermeasures
  • Treatment with botanical preparations within 2 weeks prior to treatment
  • Certain autoimmune diseases, some types will be permitted
  • Allergy or sensitivity to study drug components
  • History of interstitial lung disease
  • Severe hypersensitivity to another monoclonal antibody
  • Has received radiotherapy within 2 weeks of start of study treatment
  • Has received a live vaccine within 30 days prior to first dose of study drug
  • History of non-infectious pneumonitis
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study
  • Other serious or uncontrolled medical disorders
  • Known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study

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): NCT04336241


Contacts
Layout table for location contacts
Contact: Clinical Trials at Replimune +1 44 1235 242 488 Clinicaltrials@replimune.com

Locations
Layout table for location information
United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust Recruiting
Bebington, Merseyside, United Kingdom, CH63 4JY
Contact: Joseph Sacco       joseph.sacco@nhs.net   
The Royal Marsden NHS Foundation Trust Recruiting
London, United Kingdom, SW3 6JJ
Contact: Kevin Harrington       Kevin.Harrington@icr.ac.uk   
Churchill Hospital Recruiting
Oxford, United Kingdom, OX3 9DU
Contact: Mark Middleton       mark.middleton@oncology.ox.ac.uk   
Royal Marsden Hospital Recruiting
Sutton, United Kingdom, SM2 5PT
Contact: Kevin Harrington, MD       Kevin.Harrington@icr.ac.uk   
Sponsors and Collaborators
Replimune Inc.
Investigators
Layout table for investigator information
Study Director: Selda Samakoglu, MD Replimune Inc.
Layout table for additonal information
Responsible Party: Replimune Inc.
ClinicalTrials.gov Identifier: NCT04336241    
Other Study ID Numbers: RP2-001-18
First Posted: April 7, 2020    Key Record Dates
Last Update Posted: May 7, 2021
Last Verified: May 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action