Clinical trial NCT06014086: Intratumoral PH-762 for Cutaneous Carcinoma
Official title: Dose Escalation Study of Neoadjuvant Intratumoral PH-762 for Cutaneous Squamous Cell Carcinoma, Melanoma, or Merkel Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Squamous Cell Carcinoma of the Skin
Malignant Melanoma of Skin
Merkel Cell Carcinoma of Skin
Lead sponsor: Phio Pharmaceuticals Inc.
Sponsor class: INDUSTRY
Collaborators: name: Prosoft Clinical
First posted: 2023-08-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Key Inclusion Criteria:

* Histologically confirmed cutaneous squamous cell carcinoma (cSCC), melanoma, or Merkel cell carcinoma, meeting one of the following criteria:

  * cSCC, resectable local tumors: must be Stage II or lower, amenable to curative resection and in a location where acceptable surgical margins are anticipated
  * cSCC, unresectable local tumors: must be Stage II or lower, tumor has been unresponsive to prior radiation therapy or is not a candidate for curative radiation therapy
  * cSCC, metastatic disease: disease has progressed during or following prior checkpoint inhibitor therapy (anti-PD-1 or anti-PD-L1 antibody)
  * Melanoma, metastatic disease: Stage IV disease with a cutaneous lesion that has progressed during or following checkpoint inhibitor therapy (anti-PD-1/-PD-L1), and if BRAF-mutation is present, has progressed during or following prior treatment with anti-BRAF + MEK therapy
  * Merkel cell carcinoma, metastatic disease: Stage IV disease with a cutaneous lesion that has progressed during or following checkpoint inhibitor therapy (anti-PD-1/PD-L1)
* A minimum of one tumor of ≥ 1.0 cm and \< 3.0 cm in longest dimension that is accessible (with or without imaging guidance) for intratumoral injection and for biopsy and surgical excision must be present. The tumor is not necrotic, hemorrhagic, or friable, and is not within 2 cm of the eye or within 0.5 cm of or on the lip (including the vermilion border) and is not in a mucosal or visceral location.

Key Exclusion Criteria:

* Other malignancy within prior 3 years, with certain exceptions.
* Current cancer chemotherapy, radiation therapy, immunotherapy, or biologic therapy.
* Any serious or uncontrolled medical disorder including auto-immune disease that may increase the risk associated with study participation or study drug administration, or interfere with the interpretation of study results.
* Females who are pregnant or are breastfeeding.

Primary outcomes:
measure: Adverse Events
timeFrame: 16 weeks
Secondary outcomes:
measure: Pharmacokinetics: maximum plasma concentration (Cmax)
timeFrame: 3.5 weeks
measure: Pharmacokinetics: time to maximum plasma concentration (Tmax)
timeFrame: 3.5 weeks
measure: Pharmacokinetics: area under the curve to last quantifiable plasma concentration (AUClast)
timeFrame: 3.5 weeks
measure: Pathologic response
timeFrame: 5 weeks
measure: Tumor burden
timeFrame: 5 weeks
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: San Diego
country: United States
facility: Paradigm Clinical Research
state: California
city: Delray Beach
country: United States
facility: Integrity Research
state: Florida
city: Columbus
country: United States
facility: Centricity Research
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Department of Dermatology
state: Pennsylvania
Study officials:
affiliation: Phio Pharmaceuticals Inc.
name: Linda Mahoney
role: STUDY_DIRECTOR
References: