An Open-Label, Multicenter, Phase 1B/2 Study of RP1 in Solid Organ and Hematopoietic Cell Transplant Recipients With Advanced Cutaneous Malignancies (ARTACUS)
The purpose of this study is to assess the safety and efficacy of RP1 (administered into the tumor) in 90 patients who have received an organ transplant in the past and currently have skin cancer. The skin cancer is either locally advanced (large tumors in the skin, muscles or nerves) or metastatic (spread to other parts of the body). This study will consist of a 28-day Screening Period, a Treatment Period, and a Follow-up Period. During the Treatment Period, patients will be dosed with RP1 every two weeks for up to 2 years (104 weeks). Tumor measurements will be done approximately every 8 weeks (and additionally if needed) until progressive disease, start of subsequent anticancer therapy, or completion/discontinuation of the study. During the Follow-up Period, patients will visit the clinic at 30, 60, and 100-150 days after their last dose of RP1 for safety and quality of life assessments. Patients will continue follow-up for up to 3 years from the day of the last patient's first dose.
• 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.
• Male or female at birth and at least 18 years of age prior to signing informed consent.
• Solid organ or allogeneic hematopoietic cell transplant patients with histologically or cytologically confirmed recurrent, cutaneous malignancies including locally advanced CSCC, metastatic (to skin, soft tissue, or lymph nodes) or locally advanced BCC, metastatic or locally advanced MCC, and melanoma.
• Patients must have progressed or experienced recurrence from previous local resection and/or prior radiation.
• Documentation from the patient's transplant physician confirming that the patient's allograft is stable. For dual transplant recipients, a failure of 1 of the transplanted organs is allowed.
• Patients for whom surgical or radiation treatment of lesions is contraindicated or are considered to be inoperable.
• Patients must have at least 1 measurable tumor of at least 1 cm in longest diameter. All measurable lesions identified at screening must be injectable and planned to be injected during the course of the study.
• ECOG performance status of at most 1.
• Adequate allograft function as determined by functional testing and as confirmed by the transplant clinician.
∙ For renal transplant recipients, patients must have serum creatinine increase of \< 30% mean increase over the past 6 months.
‣ For lung transplant recipients, patients must have stable forced exploratory volume in 1 second (FEV1) of at least 50% predicted with no more than a 10% decline in the absolute FEV1 over the past 12 months.
‣ For cardiac transplant recipients, patients must have:
∙ ci. At least 50% ejection fraction with not more than an absolute change of 5% over the past 12 months. If the absolute change in ejection fraction is greater than 5% and there is no clinical suspicion for rejection by the transplant center, left ventricular ejection fraction (LVEF) stability needs to be shown by a repeat echo within 28 days after the most recent ECHO.
∙ cii. No evidence of hemodynamically or angiographically significant cardiac allograft vasculopathy (CAV) (i.e., patients must not have CAV2 or CAV3), or no ischemia by appropriate diagnostic imaging over the past 12 months.
‣ For patients with stable pancreas transplant, amylase and lipase should be ≤ 3 x upper limit of normal (ULN) for at least 6 months prior to enrollment.
⁃ Adequate hepatic function
⁃ Adequate renal function as indicated by a serum creatinine or estimated glomerular filtration rate (eGFR) determined based on the Chronic Kidney Disease-Epidemiology Collaboration equation.
⁃ Adequate hematologic function
⁃ Adequate coagulation parameters
⁃ Anticipated life expectancy \> 6 months.
⁃ Have provided either formalin-fixed, paraffin-embedded (FFPE) tissue block and/or unstained tumor tissue sections, obtained within 90 days prior to enrollment, with an associated pathology report, which must be submitted to the central laboratory for inclusion or a fresh excisional, incisional, or core needle biopsy taken prior to dosing on C1D1 if an archival biopsy (collected within 90 days prior to enrollment) is not available.
⁃ Female and male patients (at birth) who meet the following criteria:
• Female patients are eligible if not pregnant or breastfeeding and if one of the following applies 1) is a woman of non-childbearing potential (WNCBP) OR 2) is a woman of childbearing potential (WOCBP) and must agree to use a highly effective contraception method during the treatment period and for at least 90 days after last dose of RP1.
∙ Male patients are eligible if they agree to the following during the study intervention period and for at least 90 days after the last dose of RP1: refrain from donating fresh unwashed semen plus either be abstinent from intercourse where pregnancy can occur OR must agree to use external condom and advise their partner to use a highly effective method of contraception.