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

Phase 1

Recruiting

• Conditions: Melanoma; Cutaneous Squamous Cell Carcinoma; Basal Cell Carcinoma; Merkel Cell Carcinoma
• Interventions: Biological: RP1, intra-tumoral injection, oncolytic virus

• Registration Number: NCT04349436
• Lead Sponsor: 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, 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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-04-14
• Study First Submitted QC: 2020-04-14
• Study First Posted: 2020-04-16
• Study Start: 2020-05-15
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-19
• Last Update Posted: 2024-12-24
• Primary Completion: 2027-09
• Study Completion: 2028-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 65

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RP1, intra-tumoral injection, oncolytic virus	RP1, intra-tumoral injection, oncolytic virus	RP1 administered as an intra-tumoral injection every 2 weeks.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Disease control rate (DCR) by investigator review	36 months
Quality of life (QoL), as determined by patient-reported outcomes	36 months
Disease-free Survival	36 months
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
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
To asses the efficacy of RP1 as determined by ORR in all transplant recipients treated, by investigator review	36 months
Biologic activity as assessed by changes in individual tumor sizes, erythema, inflammation and necrosis	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
Clinical benefit rate defined as the rate of Complete Response (CR), Partial Response (PR), or Stable Disease (SD)	36 months

Trial Locations

Locations (20)

Medical Dermatology Specialists; 🇺🇸 Phoenix, Arizona, United States

University of California, San Diego; 🇺🇸 La Jolla, California, United States

University of California, Los Angeles; 🇺🇸 Los Angeles, California, United States

UCSF, Helen Diller Family Comprehensive Cancer Center; 🇺🇸 San Francisco, California, United States

University of Colorado Cancer Center School of Medicine; 🇺🇸 Aurora, Colorado, United States

University of Miami Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Rochester Dermatologic Surgery; 🇺🇸 New York, New York, United States

University of North Carolina Lineberger Comprehensive Cancer Center; 🇺🇸 Chapel Hill, North Carolina, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

The Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

VCU Massey Cancer Center; 🇺🇸 Richmond, Virginia, United States