A Phase 1B/2 Study of RP1 in Solid Organ Transplant Patients With Advanced Cutaneous Malignancies (ARTACUS)

An Open-Label, Multicenter, Phase 1B/2 Study of RP1 in Solid Organ and Hematopoietic Cell Transplant Recipients With Advanced Cutaneous Malignancies

This Phase 1B/2 study is a multicenter, open-label, study of RP1 to investigate the (a) objective response rate, in addition to (b) safety and tolerability of RP1 for the treatment of advanced cutaneous malignancies in up to 65 evaluable organ transplant recipients. This will include patients with either previous renal, hepatic, heart, lung, or other solid organ transplantation or hematopoietic cell transplant and experiencing subsequent documented locally advanced or metastatic cutaneous malignancies. The study will enroll a total of 65 evaluable patients. Patients will participate up to approximately 3 years including a 28-day screening period, up to approximately 1 year treatment period, and a 2-year follow-up period.

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Merkel Cell Carcinoma; Basal Cell Carcinoma; Cutaneous Squamous Cell Carcinoma
• Intervention / Treatment: Biological: RP1, intra-tumoral injection, oncolytic virus

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 1B/2, open label, multicenter, trial evaluating the objective response rate and the safety and tolerability, biodistribution, shedding, and preliminary efficacy of RP1 in adult hepatic, renal, heart, lung, other solid organs, or hematopoietic cell transplant recipients who subsequently experienced advanced or metastatic cutaneous malignancies. Patients will be dosed with RP1 by direct or ultrasound guided intra-tumoral injection into superficial, subcutaneous or nodal tumors. No transplanted organs will be injected.

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials at Replimune; Phone Number: 1-781-222-9570; Email: Clinicaltrials@replimune.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Recruiting
      • Medical Dermatology Specialists
      • Principal Investigator: Nathalie Zeitouni, MD
  • California
    • La Jolla, California, United States, 92093
      • Recruiting
      • University of California, San Diego
      • Principal Investigator: Gregory Daniels, MD
    • Los Angeles, California, United States, 90024
      • Recruiting
      • University of California, Los Angeles
      • Principal Investigator: Wanxing Chai-Ho, MD
    • San Francisco, California, United States, 94143
      • Recruiting
      • UCSF, Helen Diller Family Comprehensive Cancer Center
      • Principal Investigator: Katy Tsai, MD
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Cancer Center School of Medicine
      • Principal Investigator: Theresa Medina, MD
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami Sylvester Comprehensive Cancer Center
      • Principal Investigator: Jennifer Tang, MD
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Principal Investigator: Nikhil Khushalani, MD
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago
      • Principal Investigator: Diana Bolotin, MD
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Withdrawn
      • University of Michigan
  • New York
    • New York, New York, United States, 10032
      • Withdrawn
      • Columbia University Medical Center
    • New York, New York, United States, 14564
      • Recruiting
      • Rochester Dermatologic Surgery
      • Principal Investigator: Ibrahim Sherrif, MD, PhD
  • North Carolina
    • Durham, North Carolina, United States, 27708
      • Recruiting
      • Duke University
      • Principal Investigator: Meenal Kheterpal, MD
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • University of Cincinnati
      • Principal Investigator: Trisha Wise-Draper, MD
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University Comprehensive Cancer Center
      • Principal Investigator: Claire Verschraegen, MD
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh Medical Center
      • Principal Investigator: Diwakar Davar, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Principal Investigator: Michael Migden, MD
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Withdrawn
      • VCU Massey Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. 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.
2. Patients with histologically or cytologically confirmed recurrent, locally advanced or metastatic (to skin, soft tissue or lymph nodes) cutaneous malignancies, including CSCC, basal cell carcinoma, Merkel cell carcinoma, and melanoma
3. Patients must have progressed following local resection, prior radiation, topical or systemic therapies.
4. Documentation from the patient's transplant physician confirming that the patient's allograft is stable.
5. Patients for whom surgical or radiation treatment of lesions is contraindicated.
6. At least 1 lesion that is measurable and injectable by study criteria (tumor of ≥1cm in longest diameter or ≥1.5 cm in shortest diameter for lymph nodes).
7. Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
8. Anticipated life expectancy > 6 months
9. Baseline ECG without evidence of acute ischemia.
10. All patients must consent to provide archived or newly obtained tumor material (either formalin-fixed, paraffin-embedded [FFPE] block or 20 unstained slides).

Key Exclusion Criteria:

1. Prior treatment with an oncolytic therapy.
2. Patients with visceral metastases.
3. Patients with active herpetic infections or prior complications of HSV-1 infection (e.g., herpetic keratitis or encephalitis).
4. Patients with a history of organ graft rejection within 12 months.
5. Had systemic infection requiring intravenous (IV) antibiotics or anti-virals, or other serious infection within 60 days prior to dosing.
6. Patients who require intermittent or chronic use of systemic (oral or intravenous) anti-virals with known anti-herpetic activity (e.g., acyclovir) unless for organ allograft preservation.
7. Patients requiring CTLA-4-Ig medications.
8. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments beyond that required for maintenance allograft rejection prevention. The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism that requires only hormone replacement, or psoriasis that does not require systemic treatment.
9. Active infection with hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV).
10. Any history of transplant-related viral infections, such as BKV, EBV or CMV, within 3 months of study entry. Patients with a history of hepatitis B or C virus must have undetectable viral load within 3 months of study entry.
11. Patients with a condition requiring an increase in the patient's usual immunosuppressive medications within 60 days of study treatment.
12. Known active CNS metastases and/or carcinomatous meningitis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RP1, intra-tumoral injection, oncolytic virus; RP1 administered as an intra-tumoral injection every 2 weeks.	Biological: RP1, intra-tumoral injection, oncolytic virus; Genetically modified herpes simplex type 1 virus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Safety Outcome Measure	Assess the safety and tolerability of single-agent RP1 in solid organ transplant patients with cutaneous malignancies by incidence of subjects with treatment-emergent adverse events	36 months
Primary Efficacy Outcome Measure	The objective response rate (ORR) according to investigator assessment using modified RECIST version 1.1.	36 months
Incidence of subjects with treatment-emergent adverse events greater than or equal to Grade 3		36 months
Incidence of subjects with Serious adverse events (SAEs)		36 months
Incidence of subjects with fatal adverse events		36 months
Treatment-emergent adverse events requiring withdrawal from IP and incidence of organ allograft rejection		36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR) by investigator among subjects who experience Complete Response (CR) or Progressive Disease (PD)		36 months
CR rate by investigator assessment		36 months
Disease control rate (DCR) by investigator review		36 months
Clinical benefit rate defined as the rate of Complete Response (CR), Partial Response (PR), or Stable Disease (SD)		36 months
Progression Free Survival (PFS) by investigator review Duration of clinical benefit (DOCB) during active treatment and for up to one year after last treatment by investigator review		36 months
Overall survival (OS) at one year and two years		36 months
3-year survival rate of subjects		36 months
Quality of life (QoL), as determined by patient-reported outcomes		36 months
Disease-free Survival		36 months
Biologic activity as assessed by changes in individual tumor sizes, erythema, inflammation and necrosis	Percentage of patients with biopsy-proven clinical rejection and percentage of patients who require an increase in immune suppressive therapy, during active treatment and for up to 1 year after last treatment	36 months
To asses the efficacy of RP1 as determined by ORR in all transplant recipients treated, by investigator review		36 months

Collaborators and Investigators

• Sponsor: Replimune Inc.
• Investigators: Study Director: Jeannie Hou, MD, Replimune Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2020
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: April 14, 2020
• First Submitted That Met QC Criteria: April 14, 2020
• First Posted (Actual): April 16, 2020

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; DNA Virus Infections; Tumor Virus Infections; Neuroendocrine Tumors; Neoplasms, Basal Cell; Polyomavirus Infections; Carcinoma, Neuroendocrine; Carcinoma; Carcinoma, Merkel Cell; Carcinoma, Basal Cell
• Other Study ID Numbers: RPL-003-19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No