Intratumoral PH-762 for Cutaneous Carcinoma

NCT ID: NCT06014086

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-07

Study Completion Date

2026-04-30

Brief Summary

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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

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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.

Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Sequential escalating doses of PH-762.

Escalating doses of PH-762 are to be tested, with an observation period between doses.

Group Type EXPERIMENTAL

PH-762

Intervention Type DRUG

PH-762 is a potent RNAi molecule targeting PD-1.

Interventions

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PH-762

PH-762 is a potent RNAi molecule targeting PD-1.

Intervention Type DRUG

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Prosoft Clinical

OTHER

Sponsor Role collaborator

Phio Pharmaceuticals Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Linda Mahoney

Role: STUDY_DIRECTOR

Phio Pharmaceuticals Inc.

Locations

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Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

Paradigm Clinical Research

San Diego, California, United States

Site Status

Integrity Research

Delray Beach, Florida, United States

Site Status

Skin Cancer and Dermatology Institute

Reno, Nevada, United States

Site Status

Centricity Research

Columbus, Ohio, United States

Site Status

Countries

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United States

References

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Cuiffo B, Maxwell M, Yan D, Guemiri R, Boone A, Bellet D, Rivest B, Cardia J, Robert C, Fricker SP. Self-delivering RNAi immunotherapeutic PH-762 silences PD-1 to generate local and abscopal antitumor efficacy. Front Immunol. 2024 Dec 4;15:1501679. doi: 10.3389/fimmu.2024.1501679. eCollection 2024.

Reference Type DERIVED
PMID: 39697325 (View on PubMed)

Other Identifiers

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PHIO-762-2301

Identifier Type: -

Identifier Source: org_study_id