Study to Investigate the Efficacy and Safety of RP1 in Adult Patients With Organ Transplants and Advanced Skin Malignancies

NCT04349436 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: RPL-003-19
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 24

Brief Summary

The purpose of this study is to assess the safety and efficacy of RP1 (administered into the tumor) in 90 patients who have received an organ transplant in the past and currently have skin cancer. The skin cancer is either locally advanced (large tumors in the skin, muscles or nerves) or metastatic (spread to other parts of the body). This study will consist of a 28-day Screening Period, a Treatment Period, and a Follow-up Period. During the Treatment Period, patients will be dosed with RP1 every two weeks for up to 2 years (104 weeks). Tumor measurements will be done approximately every 8 weeks (and additionally if needed) until progressive disease, start of subsequent anticancer therapy, or completion/discontinuation of the study. During the Follow-up Period, patients will visit the clinic at 30, 60, and 100-150 days after their last dose of RP1 for safety and quality of life assessments. Patients will continue follow-up for up to 3 years from the day of the last patient's first dose.

Conditions

Merkel Cell Carcinoma; Basal Cell Carcinoma; Locally Advanced Cutaneous Squamous Cell Carcinoma; Cancer

Keywords

Oncolytic virus; Oncolytic Immuno-gene therapy; Carcinoma; Skin cancer; Locally Advanced CSCC; MCC; BCC

Outcome Measures

Primary Outcomes (3)

• Primary Objective for Patients with Locally Advances CSCC (laCSCC)

  The effect of RP1 on objective response rate (ORR) as assessed by Independnet Central Review (ICR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)

  36 months

• Primary Efficacy Objective for Patients with Other Skin Cancers

  The effect of RP1 on ORR as assessed by investigator review per modified RECIST 1.1 (mRECIST 1.1)

  36 months

• Primary Safety Objective for Patients with Other Skin Cancers

  The safety and tolerability of single-agent RP1 in solid organ transplant patients with other skin cancers as assessed by incidence of patients with treatment-emergent adverse events (TEAEs) and by incidence of patients with biopsy-proven allograft rejection.

  36 months

Secondary Outcomes (8)

• Duration of Response (DOR) for Patients with laCSCC

  36 months

• Progression-Free Survival (PFS) for Patients with laCSCC

  36 months

• Disease Control Rate (DCR) for Patients with laCSCC

  36 months

• ORR for Patients with laCSCC by investigator review

  36 months

• Efficacy parameters for Patients with laCSCC by investigator review

  36 months

Study Arms (1)

RP1, intra-tumoral injection, oncolytic virus

EXPERIMENTAL

RP1 administered as an intra-tumoral injection every 2 weeks.

Biological: RP1, intra-tumoral injection, oncolytic virus

Interventions

RP1, intra-tumoral injection, oncolytic virus BIOLOGICAL

Genetically modified herpes simplex type 1 virus

RP1, intra-tumoral injection, oncolytic virus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary agreement to provide written informed consent prior to any study procedures and the willingness and ability to comply with all aspects of the protocol and understand the risk to their organ allograft.
• Male or female at birth and at least 18 years of age prior to signing informed consent.
• Solid organ or allogeneic hematopoietic cell transplant patients with histologically or cytologically confirmed recurrent, cutaneous malignancies including locally advanced CSCC, metastatic (to skin, soft tissue, or lymph nodes) or locally advanced BCC, metastatic or locally advanced MCC, and melanoma.
• Patients must have progressed or experienced recurrence from previous local resection and/or prior radiation.
• Documentation from the patient's transplant physician confirming that the patient's allograft is stable. For dual transplant recipients, a failure of 1 of the transplanted organs is allowed.
• Patients for whom surgical or radiation treatment of lesions is contraindicated or are considered to be inoperable.
• Patients must have at least 1 measurable tumor of at least 1 cm in longest diameter. All measurable lesions identified at screening must be injectable and planned to be injected during the course of the study.
• ECOG performance status of at most 1.
• Adequate allograft function as determined by functional testing and as confirmed by the transplant clinician.
• For renal transplant recipients, patients must have serum creatinine increase of \< 30% mean increase over the past 6 months.
• For lung transplant recipients, patients must have stable forced exploratory volume in 1 second (FEV1) of at least 50% predicted with no more than a 10% decline in the absolute FEV1 over the past 12 months.
• For cardiac transplant recipients, patients must have:
• ci. At least 50% ejection fraction with not more than an absolute change of 5% over the past 12 months. If the absolute change in ejection fraction is greater than 5% and there is no clinical suspicion for rejection by the transplant center, left ventricular ejection fraction (LVEF) stability needs to be shown by a repeat echo within 28 days after the most recent ECHO.
• cii. No evidence of hemodynamically or angiographically significant cardiac allograft vasculopathy (CAV) (i.e., patients must not have CAV2 or CAV3), or no ischemia by appropriate diagnostic imaging over the past 12 months.
• For patients with stable pancreas transplant, amylase and lipase should be ≤ 3 x upper limit of normal (ULN) for at least 6 months prior to enrollment.

You may not qualify if:

• Prior treatment with an oncolytic therapy or checkpoint inhibitor.
• Patients with visceral metastases.
• Active significant herpetic infections or prior complications of HSV-1 infection (e.g., herpetic keratitis or encephalitis). Patients requiring use of systemic (oral/intravenous \[IV\]) antiviral agents with known antiherpetic activity.
• Patients requiring concurrent treatment with cytotoxic T-lymphocyte antigen 4-Ig (CTLA-4-Ig) medications.
• Had systemic infection requiring IV antibiotics or other serious infection within 14 days prior to dosing.
• Patients with an active, known, or suspected autoimmune disease that requires systemic immunosuppressive treatment beyond immunosuppressive medications required for maintenance of allograft rejection prevention.
• Patients with a history of any positive test result for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating the presence of the virus, or human immunodeficiency virus (HIV) positive. Patients with a history of HBV or HCV must have undetectable viral load within 3 months of study entry.
• A history of transplant-related viral infections such as BK virus (BKV), Epstein-Barr virus (EBV), or cytomegalovirus (CMV) requiring treatment or modification to immunosuppression within 3 months of study entry.
• Had clinically significant cardiovascular disease within 6 months from first dose of RP1, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction or stroke/transient ischemic attack or significant cardiac arrhythmias associated with hemodynamic instability.
• Radiation therapy within 14 days of first dose of RP1, or topical or any systemic therapy within 30 days of the first dose of RP1.
• Documented history of allergic reactions or acute hypersensitivity reaction attributed to RP1 or to any of the excipients.
• Females who have a positive serum beta-human chorionic gonadotropin (β-hCG) test for pregnancy (at screening within 72 hours before dosing), or a positive urine pregnancy test on C1D1.
• Any active malignancy within 3 years of the date of first planned dose of RP1, except for the specific cancer under investigation in this study and tumors with negligible risk of metastasis or death.
• Any acute or chronic psychiatric problems, alcohol abuse, or substance abuse disorders that, in the opinion of the investigator, would interfere with the patient's ability to comply with the requirements of the study.
• Any co-morbidity, physical examination finding, metabolic dysfunction, or clinical laboratory abnormality that, in the opinion of the investigator, renders the patient unsuitable for participation due to safety risks or potential to affect interpretation of results of the study.

Sponsors & Collaborators

• Replimune, Inc.: lead

Study Sites (24)

Medical Dermatology Specialists

Phoenix, Arizona, 85006, United States

Location

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

University of California, San Diego

La Jolla, California, 92093, United States

Location

University of California, Los Angeles

Los Angeles, California, 90024, United States

Location

UCSF, Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94143, United States

Location

University of Colorado Cancer Center School of Medicine

Aurora, Colorado, 80045, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Rochester Dermatologic Surgery

New York, New York, 14564, United States

Location

University of North Carolina Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Duke University

Durham, North Carolina, 27708, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Tennessee Medical Center at Knoxville

Knoxville, Tennessee, 37920, United States

Location

University of Texas Southwestern

Dallas, Texas, 75235, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Carcinoma, Merkel Cell; Carcinoma, Basal Cell; Neoplasms; Carcinoma; Skin Neoplasms

Interventions

MAPRE1 protein, human

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Basal Cell; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Jeannie Hou, MD

  Replimune, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: RP1 injection

Study Record Dates

• First Submitted: April 14, 2020
• First Posted: April 16, 2020
• Study Start: May 15, 2020
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): November 1, 2029
• Last Updated: April 22, 2026

Record last verified: 2026-04

Locations

US (24)