A Phase 1B Study of RP1 in Transplant Patients With Advanced Cutaneous Squamous Cell Carcinoma (ARTACUS)

• ClinicalTrials.gov Identifier: NCT04349436
• Recruitment Status: Recruiting
• First Posted: April 16, 2020
• Last Update Posted: September 14, 2021
• Sponsor: Replimune Inc.
• Information provided by (Responsible Party): Replimune Inc.

Study Description

Brief Summary:

This Phase 1B study is a multicenter, open-label, study of RP1 to investigate the safety and tolerability of RP1 for the treatment of advanced CSCC in up to 30 evaluable organ transplant recipients. This will include patients with either previous renal or hepatic allograft transplantation and experiencing subsequent documented locally advanced or metastatic CSCC. The study will enroll a total of 30 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	Biological: RP1, intra-tumoral injection, oncolytic virus	Phase 1

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, open label, multicenter, trial evaluating the safety and tolerability, biodistribution, shedding, and preliminary efficacy of RP1 in adult hepatic and renal transplant recipients who subsequently experienced advanced or metastatic CSCC. 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: 30 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 Study of RP1 in Organ Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma (CSCC)
• Actual Study Start Date: May 15, 2020
• Estimated Primary Completion Date: February 2024
• Estimated Study Completion Date: June 2024

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. Percentage of subjects with treatment-emergent adverse events greater than or equal to Grade 3 [ Time Frame: 36 months ]
2. Percentage of subjects with Serious adverse events (SAEs) [ Time Frame: 36 months ]
3. Percentage of subjects with Treatment-emergent adverse events [ Time Frame: 36 months ]
4. Percentage of subjects experiencing organ allograft rejection [ Time Frame: 36 months ]

Secondary Outcome Measures :

1. Overall response rate (ORR) [ Time Frame: 36 months ]
2. Median Duration of response (DOR) of subjects [ Time Frame: 36 months ]
3. Percentage of subjects with Complete response (CR) [ Time Frame: 36 months ]
4. Percentage of subjects who receive a clinical benefit rate defined as the rate of Complete Response (CR), Progressive Disease (PR), or Stable Disease (SD) [ Time Frame: 36 months ]
5. Median duration of clinical benefit of subjects [ Time Frame: 36 months ]
6. Median disease-free survival of subjects [ Time Frame: 36 months ]
7. 3-year survival rate of subjects [ Time Frame: 36 months ]
8. Change in subject reported quality of life [ Time Frame: 36 months ]
9. Changes subjects experience in individual tumor sizes, erythema, inflammation and necrosis [ Time Frame: 36 months ]
   Changes in tumor size will be evaluated using radiologic scans and calipers for externally visible lesions
10. To assess the incidence and severity of graft rejection, and the need for increase in immune suppressive therapy,during active treatment and for up to 1 year after last treatment [ Time Frame: 24 months ]
    Graft rejection will be assessed by clinical presentation and using the standard measures of kidney/liver function (BUN/Creatinine in the former, AST/ALT/bilirubin in the latter) to ensure that there is no evidence of allograft failure.

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 squamous cell carcinoma, who have progressed following local resection or one local (i.e., topical) medical therapy.
3. Patients who are renal or hepatic organ allograft recipients on a stable immunosuppressive regimen for at least 12 months prior to study participation with stable renal and/or hepatic function. NOTE: Patients who require CTLA-4-Ig medications are excluded.
4. Patients for whom surgical or radiation treatment of lesions is contraindicated.
5. 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).
6. Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
7. Anticipated life expectancy > 6 months
8. Baseline ECG without evidence of acute ischemia.
9. 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 or more than one prior CSCC-directed local/topical therapy.
2. Prior systemic anti-cancer treatment for CSCC.
3. Patients with visceral metastases.
4. Patients with active herpetic infections or prior complications of HSV-1 infection (e.g. herpetic keratitis or encephalitis).
5. Patients with a history of organ graft rejection within 12 months.
6. Patients with an ANC < 1.0 x 109/L at any point within 3 months of starting therapy.
7. Had systemic infection requiring intravenous (IV) antibiotics or anti-virals, or other serious infection within 60 days prior to dosing.
8. 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.
9. Patients requiring CTLA-4-Ig medications.
10. 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.
11. Active infection with hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV).
12. Any history of transplant-related viral infections, such as BK, 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.
13. Patients with a condition requiring an increase in the patient's usual immunosuppressive medications within 60 days of study treatment.
14. 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; Not yet recruiting

Miami, Florida, United States, 33136

Principal Investigator: Jose Lutzky, MD

United States, Illinois

University of Chicago; Recruiting

Chicago, Illinois, United States, 60637

Contact 773-702-7696 uchicagodermtrial@uchospitals.edu

Principal Investigator: Diana Bolotin, MD

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: Clarie 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: Henry Castro, 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: September 14, 2021
• Last Verified: September 2021

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

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Squamous Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell