Phio Pharmaceuticals' PH-762 Shows Promising Results in Phase 1b Skin Cancer Trial with 37.5% Complete Response Rate
核心洞察
Phio Pharmaceuticals' investigational siRNA therapeutic PH-762 achieved complete tumor clearance in 37.5% of cutaneous squamous cell carcinoma (搜索) patients in an ongoing Phase 1b trial.
The intratumoral treatment demonstrated a favorable safety profile with no dose-limiting toxicities or immune-related adverse events across a 20-fold dose escalation.
PH-762 utilizes Phio's INTASYL gene silencing platform to target PD-1 (搜索) locally within tumors, offering a potential non-surgical alternative for skin cancer (搜索) treatment.
Phio Pharmaceuticals Corp. has announced positive pathology results from its ongoing Phase 1b dose-escalation trial of PH-762, an investigational small interfering RNA (siRNA) therapeutic targeting programmed cell death protein 1 (PD-1 (搜索)). The study demonstrates encouraging efficacy signals and a favorable safety profile in patients with various skin cancers.
Trial Design and Patient Population
The open-label Phase 1b trial (NCT06014086) is evaluating the safety, tolerability, and preliminary efficacy of PH-762 administered via intratumoral injection. The study includes patients with cutaneous squamous cell carcinoma (搜索) (cSCC; Stages I, II, and IV), stage IV melanoma (搜索), and stage IV Merkel cell carcinoma (搜索). The investigational protocol consists of 4 weekly intratumoral injections, with pathologic response assessment approximately 5 weeks after the first dose.
As of the most recent update, 18 patients have completed treatment: 16 with cSCC, 1 with metastatic melanoma (搜索), and 1 with metastatic MCC. The study employs a dose-escalation design across 5 cohorts to determine safety and establish a maximum tolerated dose.
Efficacy Results Show Strong Response Rates
Among the 16 cSCC patients, cumulative histopathologic outcomes demonstrated significant tumor clearance:
- 6 patients (37.5%) achieved complete response with 100% tumor clearance
- 2 patients (12.5%) showed near complete response with >90% clearance
- 2 patients (12.5%) demonstrated partial response with >50% clearance
- 6 patients (37.5%) were classified as non-responders with <50% clearance
Additionally, 1 patient with metastatic Merkel cell carcinoma (搜索) exhibited a partial response (>50% clearance), while the patient with metastatic melanoma (搜索) demonstrated a non-response. Importantly, no patients across the study have shown clinical disease progression following treatment to date.
The fifth and final dose cohort, comprising 3 patients with cSCC, showed particularly promising results with 100% tumor clearance in 1 patient, >90% clearance in another, and >50% clearance in the third, suggesting a potential dose-response relationship.
Safety Profile Supports Continued Development
The Safety Monitoring Committee conducted a pre-specified review of safety outcomes for the initial three patients in the fifth cohort and confirmed no dose-limiting toxicities (DLTs) or clinically significant treatment-emergent adverse events at the highest tested dose concentration.
"We are pleased with the continuing safety profile of PH-762 throughout dose escalation to approximately a 20-fold increase versus that received in the first cohort," said Mary Spellman, MD, Phio's acting Chief Medical Officer. "PH-762 has been well tolerated in this trial, without relevant immune-related adverse events or other toxicities."
According to Phio, no DLTs or clinically meaningful immune-related or systemic toxicities have been observed at any dose level throughout the cumulative dose escalation.
Novel Mechanism Targets Local Immune Response
PH-762 is designed to silence PD-1 (搜索) mRNA locally within the tumor microenvironment using Phio's INTASYL (Interfering RNA Transfection via Self-Delivering siRNA) platform. Unlike systemically administered checkpoint inhibitors that act on circulating T cells, intratumoral PH-762 seeks to modulate immune checkpoint signaling directly within the tumor, potentially amplifying anti-tumor immune responses while minimizing systemic immune-related toxicity.
The INTASYL compounds are designed to enhance the body's immune cells to more effectively kill cancer cells, representing a potential non-surgical treatment option for skin cancers.
Clinical Significance and Future Directions
Given that cutaneous squamous cell carcinoma (搜索) is one of the most common non-melanoma (搜索) skin cancers, with rising incidence and increasing treatment complexity in elderly and immunocompromised populations, a well-tolerated, non-surgical, localized therapy could represent a significant therapeutic advance, particularly for patients who are poor surgical candidates or wish to avoid disfiguring procedures.
The ongoing study continues to collect data to refine optimal dosing parameters, characterize immune-related pharmacodynamics, and assess durability of response. Phio may continue to screen and treat additional patients within the fifth cohort to strengthen the dataset before advancing to later-phase clinical evaluation.
The company stated that future studies will likely explore combination strategies with systemic immunotherapies or expand indications to other accessible solid tumors. While the Phase 1b results remain preliminary, the combination of encouraging pathologic response rates and a favorable safety profile supports further investigation of PH-762 as a novel approach to treating cutaneous malignancies.