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

• ClinicalTrials.gov Identifier: NCT04349436
• Recruitment Status: Recruiting
• First Posted: April 16, 2020
• Last Update Posted: February 1, 2023
• Sponsor: Replimune Inc.
• Information provided by (Responsible Party): Replimune Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cutaneous Squamous Cell Carcinoma; Merkel Cell Carcinoma; Basal Cell Carcinoma; Melanoma	Biological: RP1, intra-tumoral injection, oncolytic virus	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 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 65 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: RP1 injection
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter, Phase 1B/2 Study of RP1 in Solid Organ and Hematopoietic Cell Transplant Recipients With Advanced Cutaneous Malignancies
• Actual Study Start Date: May 15, 2020
• Estimated Primary Completion Date: September 2027
• Estimated Study Completion Date: January 2028

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Primary Safety Outcome Measure [ Time Frame: 36 months ]
   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
2. Primary Efficacy Outcome Measure [ Time Frame: 36 months ]
   The objective response rate (ORR) according to investigator assessment using modified RECIST version 1.1.
3. Incidence of subjects with treatment-emergent adverse events greater than or equal to Grade 3 [ Time Frame: 36 months ]
4. Incidence of subjects with Serious adverse events (SAEs) [ Time Frame: 36 months ]
5. Incidence of subjects with fatal adverse events [ Time Frame: 36 months ]
6. Treatment-emergent adverse events requiring withdrawal from IP and incidence of organ allograft rejection [ Time Frame: 36 months ]

Secondary Outcome Measures :

1. Duration of response (DOR) by investigator among subjects who experience Complete Response (CR) or Progressive Disease (PD) [ Time Frame: 36 months ]
2. CR rate by investigator assessment [ Time Frame: 36 months ]
3. Disease control rate (DCR) by investigator review [ Time Frame: 36 months ]
4. Clinical benefit rate defined as the rate of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) [ Time Frame: 36 months ]
5. 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 [ Time Frame: 36 months ]
6. Overall survival (OS) at one year and two years [ Time Frame: 36 months ]
7. 3-year survival rate of subjects [ Time Frame: 36 months ]
8. Quality of life (QoL), as determined by patient-reported outcomes [ Time Frame: 36 months ]
9. Biologic activity as assessed by changes in individual tumor sizes, erythema, inflammation and necrosis [ Time Frame: 36 months ]
   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
10. Disease-free Survival [ Time Frame: 36 months ]
11. To asses the efficacy of RP1 as determined by ORR in all transplant recipients treated, by investigator review [ Time Frame: 36 months ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Clinical Trials at Replimune; 1-781-222-9570; Clinicaltrials@replimune.com

Locations

United States, California

University of California, San Diego; Recruiting

La Jolla, California, United States, 92093

Principal Investigator: Gregory Daniels, MD

University of California, Los Angeles; Recruiting

Los Angeles, California, United States, 90024

Principal Investigator: Wanxing Chai-Ho, MD

UCSF, Helen Diller Family Comprehensive Cancer Center; Recruiting

San Francisco, California, United States, 94143

Principal Investigator: Katy Tsai, MD

United States, Colorado

University of Colorado Cancer Center School of Medicine; Recruiting

Aurora, Colorado, United States, 80045

Principal Investigator: Theresa Medina, MD

United States, Florida

University of Miami Sylvester Comprehensive Cancer Center; Recruiting

Miami, Florida, United States, 33136

Principal Investigator: Jennifer Tang

United States, Illinois

University of Chicago; Recruiting

Chicago, Illinois, United States, 60637

Principal Investigator: Diana Bolotin, MD

United States, New York

Columbia University Medical Center; Recruiting

New York, New York, United States, 10032

Principal Investigator: Shaheer Khan, DO

Rochester Dermatologic Surgery; Recruiting

New York, New York, United States, 14564

Contact: Ibrahim Sherrif

United States, North Carolina

Duke University; Recruiting

Durham, North Carolina, United States, 27708

Principal Investigator: Meenal Kheterpal, MD

United States, Ohio

University of Cincinnati; Recruiting

Cincinnati, Ohio, United States, 45267

Principal Investigator: Trisha Wise-Draper, MD

The Ohio State University Comprehensive Cancer Center; Recruiting

Columbus, Ohio, United States, 43210

Principal Investigator: Claire Verschraegen, MD

United States, Pennsylvania

University of Pittsburgh Medical Center; Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Principal Investigator: Jason Luke, MD

United States, Texas

MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Principal Investigator: Michael Migden, MD

United States, Virginia

VCU Massey Cancer Center; Recruiting

Richmond, Virginia, United States, 23298

Principal Investigator: Andrew Poklepovic, MD

Sponsors and Collaborators

Replimune Inc.

Investigators

• Study Director: Jeannie Hou, MD; Replimune Inc.

More Information

• Responsible Party: Replimune Inc.
• ClinicalTrials.gov Identifier: NCT04349436
• Other Study ID Numbers: RPL-003-19
• First Posted: April 16, 2020
• Last Update Posted: February 1, 2023
• Last Verified: January 2023

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

Additional relevant MeSH terms:

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