Clinical trial NCT04349436: A Phase 1B/2 Study of RP1 in Solid Organ Transplant Patients With Advanced Cutaneous Malignancies
Official title: An Open-Label, Multicenter, Phase 1B/2 Study of RP1 in Solid Organ and Hematopoietic Cell Transplant Recipients With Advanced Cutaneous Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cutaneous Squamous Cell Carcinoma
Merkel Cell Carcinoma
Basal Cell Carcinoma
Melanoma
Lead sponsor: Replimune Inc.
Sponsor class: INDUSTRY
First posted: 2020-04-16
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: RP1 injection
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Primary Safety Outcome Measure
timeFrame: 36 months
measure: Primary Efficacy Outcome Measure
timeFrame: 36 months
measure: Incidence of subjects with treatment-emergent adverse events greater than or equal to Grade 3
timeFrame: 36 months
measure: Incidence of subjects with Serious adverse events (SAEs)
timeFrame: 36 months
measure: Incidence of subjects with fatal adverse events
timeFrame: 36 months
measure: Treatment-emergent adverse events requiring withdrawal from IP and incidence of organ allograft rejection
timeFrame: 36 months
Secondary outcomes:
measure: Duration of response (DOR) by investigator among subjects who experience Complete Response (CR) or Progressive Disease (PD)
timeFrame: 36 months
measure: CR rate by investigator assessment
timeFrame: 36 months
measure: Disease control rate (DCR) by investigator review
timeFrame: 36 months
measure: Clinical benefit rate defined as the rate of Complete Response (CR), Partial Response (PR), or Stable Disease (SD)
timeFrame: 36 months
measure: 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
timeFrame: 36 months
measure: Overall survival (OS) at one year and two years
timeFrame: 36 months
measure: 3-year survival rate of subjects
timeFrame: 36 months
measure: Quality of life (QoL), as determined by patient-reported outcomes
timeFrame: 36 months
measure: Biologic activity as assessed by changes in individual tumor sizes, erythema, inflammation and necrosis
timeFrame: 36 months
measure: Disease-free Survival
timeFrame: 36 months
measure: To asses the efficacy of RP1 as determined by ORR in all transplant recipients treated, by investigator review
timeFrame: 36 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Medical Dermatology Specialists
state: Arizona
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: San Francisco
country: United States
facility: UCSF, Helen Diller Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center School of Medicine
state: Colorado
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Rochester Dermatologic Surgery
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Lineberger Comprehensive Cancer Center
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Knoxville
country: United States
facility: University of Tennessee Medical Center at Knoxville
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Richmond
country: United States
facility: VCU Massey Cancer Center
state: Virginia
Study officials:
affiliation: Replimune Inc.
name: May Cho, MD
role: STUDY_DIRECTOR
References: