The goal of this clinical trial is to evaluate the safety and tolerability of intratumoral injections of PH-762 in squamous cell carcinoma, melanoma, or Merkel cell carcinomas of the skin, to understand what the body does to the PH-762, and to observe how the tumor responds to the drug. Participants will receive four injections of PH-762 at weekly intervals, into a single tumor, followed by surgical removal of the tumor approximately two weeks later.
PH-762 is a potent RNAi molecule targeting PD-1. PH-762 can inhibit the immune checkpoint PD-1 in the tumor and thereby impede tumor growth. As a preoperative therapy, it may decrease the lesion size and has the potential to improve surgical morbidity. Intratumoral immunotherapy aims to use the tumor as a 'self-vaccine'. The local immune stimulation can induce robust priming of an anti-tumor immune response while generating systemic (abscopal) tumor responses, mediated by properly activated anti-tumor immune cells in the circulation. Local delivery of immunotherapy is expected to minimize systemic exposure and off-target toxicities. This is a non-comparative study of neoadjuvant monotherapy using PD-1 targeting self-delivering RNAi (PH-762) in adult subjects with cutaneous squamous cell carcinoma, melanoma, or Merkel cell carcinoma. The study treatment consists of four intratumoral injections of PH-762 at weekly intervals, into a single tumor lesion. Excision of the tumor will occur approximately two weeks following the fourth dose of IT PH-762, and the subjects will be followed for an additional 11 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
PH-762 is a potent RNAi molecule targeting PD-1.
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
Paradigm Clinical Research
San Diego, California, United States
Integrity Research
Delray Beach, Florida, United States
Skin Cancer and Dermatology Institute
Reno, Nevada, United States
Adverse Events
Incidence, severity, seriousness and relatedness of all treatment-emergent adverse events.
Time frame: 16 weeks
Pharmacokinetics: maximum plasma concentration (Cmax)
Maximum concentration of PH-762 following intratumoral injection.
Time frame: 3.5 weeks
Pharmacokinetics: time to maximum plasma concentration (Tmax)
Time to maximum concentration of PH-762 following intratumoral injection.
Time frame: 3.5 weeks
Pharmacokinetics: area under the curve to last quantifiable plasma concentration (AUClast)
Exposure to PH-762 through last quantifiable concentration following intratumoral injection.
Time frame: 3.5 weeks
Pathologic response
Pathological response will be assessed by relative amount of viable tumor in resection specimens of the treated lesion.
Time frame: 5 weeks
Tumor burden
Change in tumor burden will be assessed per RECIST/ iRECIST guidelines for the treated lesion.
Time frame: 5 weeks
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Centricity Research
Columbus, Ohio, United States