Intratumoral PH-762 for Cutaneous Carcinoma

Trial Title: Intratumoral PH-762 for Cutaneous Carcinoma

NCT ID: NCT06014086

Condition: Squamous Cell Carcinoma of the Skin
Malignant Melanoma of Skin
Merkel Cell Carcinoma of Skin

Conditions: Official terms:
Carcinoma, Merkel Cell
Carcinoma
Melanoma
Carcinoma, Squamous Cell
Melanoma, Cutaneous Malignant

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: PH-762
Description: PH-762 is a potent RNAi molecule targeting PD-1.
Arm group label: Sequential escalating doses of PH-762.

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.

Criteria for 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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Banner MD Anderson Cancer Center

Address:
City: Gilbert
Zip: 85234
Country: United States

Status: Recruiting

Contact:
Last name: Mark I Gimbel, MD

Phone: 480-256-6444

Facility:
Name: George Washington University

Address:
City: Washington
Zip: 20037
Country: United States

Status: Recruiting

Contact:
Last name: Kendall, Research Coordinator

Phone: 202-994-1419

Facility:
Name: Integrity Research

Address:
City: Delray Beach
Zip: 33445
Country: United States

Status: Recruiting

Contact:
Last name: Monica, Research Coordinator

Phone: 561-935-9865

Facility:
Name: Centricity Research

Address:
City: Columbus
Zip: 43213
Country: United States

Status: Recruiting

Contact:
Last name: Valerie, Research Coordinator

Phone: 614-336-7880

Facility:
Name: UPMC Department of Dermatology

Address:
City: Pittsburgh
Zip: 15213
Country: United States

Status: Recruiting

Contact:
Last name: Charity, Research Coordinator

Phone: 412-647-2013

Start date: November 7, 2023

Completion date: September 2025

Lead sponsor:
Agency: Phio Pharmaceuticals Inc.
Agency class: Industry

Collaborator:
Agency: Prosoft Clinical
Agency class: Other

Source: Phio Pharmaceuticals Inc.

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06014086