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

  • Interventional
  • Recruiting
  • NCT04349436
Eligibility Details Visit Clinicaltrials.gov

An Open-Label, Multicenter, Phase 1B Study of RP1 in Organ Transplant Recipients With Advanced Cutaneous Squamous Cell Carcinoma (CSCC)

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.

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.


Age Group
18 Years and up

Accepting Healthy Volunteers?

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.
  • Non-Melanoma Skin Cancer

At a Glance

National Government IDNCT04349436


Lead SponsorReplimune Inc.

Lead PhysicianDiana Bolotin


18 Years and up