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

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: NCT04349436
Recruitment Status : Recruiting
First Posted : April 16, 2020
Last Update Posted : March 18, 2022
Sponsor:
Information provided by (Responsible Party):
Replimune Inc.

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, or lung allograft transplantation 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 and lung transplant recipients who subsequently experienced advanced or metastatic cutaneous malignanies. 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.

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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 Transplant Recipients With Advanced Cutaneous Malignancies
Actual Study Start Date : May 15, 2020
Estimated Primary Completion Date : July 2026
Estimated Study Completion Date : September 2026


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




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. 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. Biologic activity as assessed by changes in individual tumor sizes, erythema, inflammation and necrosis [ Time Frame: 24 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

  11. Disease-free Survival [ Time Frame: 36 months ]


Information from the National Library of Medicine

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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.

    Documentation from the patient's transplant physician confirming that the patient's allograft is stable.

  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.
  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.

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): NCT04349436


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

Locations
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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: 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: 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
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Study Director: Chris Ahlers, MD Replimune Inc.
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Responsible Party: Replimune Inc.
ClinicalTrials.gov Identifier: NCT04349436    
Other Study ID Numbers: RPL-003-19
First Posted: April 16, 2020    Key Record Dates
Last Update Posted: March 18, 2022
Last Verified: March 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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