Clinical Trials /

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

NCT04349436

Description:

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.

Related Conditions:
  • Skin Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1B Study of RP1 in Transplant Patients With Advanced Cutaneous Squamous Cell Carcinoma
  • Official Title: An Open-Label, Multicenter, Phase 1B Study of RP1 in Organ Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma (CSCC)

Clinical Trial IDs

  • ORG STUDY ID: RPL-003-19
  • NCT ID: NCT04349436

Conditions

  • Cutaneous Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
RP1, intra-tumoral injection, oncolytic virusRP1, intra-tumoral injection, oncolytic virus

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
RP1, intra-tumoral injection, oncolytic virusExperimentalRP1 administered as an intra-tumoral injection every 2 weeks.
  • RP1, intra-tumoral injection, oncolytic virus

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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of subjects with treatment-emergent adverse events greater than or equal to Grade 3
Time Frame:36 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:36 months
Safety Issue:
Description:
Measure:Median Duration of response (DOR) of subjects
Time Frame:36 months
Safety Issue:
Description:
Measure:Percentage of subjects with Complete response (CR)
Time Frame:36 months
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Median duration of clinical benefit of subjects
Time Frame:36 months
Safety Issue:
Description:
Measure:Median disease-free survival of subjects
Time Frame:36 months
Safety Issue:
Description:
Measure:3-year survival rate of subjects
Time Frame:36 months
Safety Issue:
Description:
Measure:Change in subject reported quality of life
Time Frame:36 months
Safety Issue:
Description:
Measure:Changes subjects experience in individual tumor sizes, erythema, inflammation and necrosis
Time Frame:36 months
Safety Issue:
Description:Changes in tumor size will be evaluated using radiologic scans and using caliphers for externally visible lesions
Measure: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
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Replimune Inc.

Last Updated

May 18, 2020