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

Melanoma Clinical Trial

— ARTACUS  

Official title:

An Open-Label, Multicenter, Phase 1B/2 Study of RP1 in Solid Organ and Hematopoietic Cell Transplant Recipients With Advanced Cutaneous Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04349436
• Other study ID #: RPL-003-19
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 15, 2020
• Est. completion date: January 2028

Study information

• Verified date: December 2023
• Source: Replimune Inc.
• Contact: Clinical Trials at Replimune
• Phone: 1-781-222-9570
• Email: Clinicaltrials[@]replimune.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 65
• Est. completion date: January 2028
• Est. primary completion date: September 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Basal Cell Carcinoma
• Carcinoma
• Carcinoma, Basal Cell
• Carcinoma, Merkel Cell
• Cutaneous Squamous Cell Carcinoma
• Melanoma
• Merkel Cell Carcinoma

Intervention

Biological:
• RP1, intra-tumoral injection, oncolytic virus
Genetically modified herpes simplex type 1 virus

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado Cancer Center School of Medicine	Aurora	Colorado
United States	University of Chicago	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Duke University	Durham	North Carolina
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of California, San Diego	La Jolla	California
United States	University of California, Los Angeles	Los Angeles	California
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Columbia University Medical Center	New York	New York
United States	Rochester Dermatologic Surgery	New York	New York
United States	Medical Dermatology Specialists	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	VCU Massey Cancer Center	Richmond	Virginia
United States	UCSF, Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Replimune Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Safety Outcome Measure	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	36 months
Primary	Primary Efficacy Outcome Measure	The objective response rate (ORR) according to investigator assessment using modified RECIST version 1.1.	36 months
Primary	Incidence of subjects with treatment-emergent adverse events greater than or equal to Grade 3		36 months
Primary	Incidence of subjects with Serious adverse events (SAEs)		36 months
Primary	Incidence of subjects with fatal adverse events		36 months
Primary	Treatment-emergent adverse events requiring withdrawal from IP and incidence of organ allograft rejection		36 months
Secondary	Duration of response (DOR) by investigator among subjects who experience Complete Response (CR) or Progressive Disease (PD)		36 months
Secondary	CR rate by investigator assessment		36 months
Secondary	Disease control rate (DCR) by investigator review		36 months
Secondary	Clinical benefit rate defined as the rate of Complete Response (CR), Partial Response (PR), or Stable Disease (SD)		36 months
Secondary	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
Secondary	Overall survival (OS) at one year and two years		36 months
Secondary	3-year survival rate of subjects		36 months
Secondary	Quality of life (QoL), as determined by patient-reported outcomes		36 months
Secondary	Biologic activity as assessed by changes in individual tumor sizes, erythema, inflammation and necrosis	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	36 months
Secondary	Disease-free Survival		36 months
Secondary	To asses the efficacy of RP1 as determined by ORR in all transplant recipients treated, by investigator review		36 months