Intratumoral PH-762 for Skin Cancer

Recruiting at 7 trial locations

Overseen By Mary C Spellman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Phio Pharmaceuticals Inc.

Must not be taking: Chemotherapy, Radiation, Immunotherapy, others

Disqualifiers: Other malignancy, Auto-immune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 6 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called PH-762 for certain types of skin cancer, such as squamous cell carcinoma, melanoma, and Merkel cell carcinoma. The main goal is to determine the treatment's safety and its effects on tumors after direct injection. Participants will receive four weekly injections, followed by surgical removal of the tumor. Suitable candidates include individuals with specific skin cancers that have not responded well to other treatments and have a tumor between 1.0 cm and 3.0 cm in size that can be safely injected and removed. As a Phase 1 trial, this research aims to understand how PH-762 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on current cancer treatments like chemotherapy, radiation, or immunotherapy.

Is there any evidence suggesting that PH-762 is likely to be safe for humans?

Research has shown that PH-762 has promising safety results from earlier studies. These studies found that PH-762, a new treatment for skin cancer, was generally well-tolerated, with most patients not experiencing serious side effects.

In trials with gradually increasing doses, PH-762 remained safe even at higher levels. A safety committee approved the continuation of these trials, indicating confidence in the treatment's safety.

Overall, while more research is needed, these early studies suggest that PH-762 is generally safe for treating skin cancers such as squamous cell carcinoma, melanoma, and Merkel cell carcinoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for skin cancer, which often involve surgery, radiation, or topical therapies, PH-762 offers a novel approach by being administered directly into the tumor. This treatment stands out due to its mechanism as a small interfering RNA (siRNA) designed to silence specific genes within the cancer cells, potentially reducing tumor growth from within. Researchers are excited about PH-762 because it targets cancer at the genetic level, offering a potentially more precise and less invasive alternative to traditional therapies.

What evidence suggests that PH-762 might be an effective treatment for skin cancer?

Research has shown that PH-762 could help treat skin cancers such as squamous cell carcinoma, melanoma, and Merkel cell carcinoma. Studies have found that PH-762, a new type of treatment, can effectively clear tumors. It targets and turns off certain proteins, allowing more immune cells to enter and help control the tumor. Early results suggest that PH-762 is safe and can shrink tumors when injected directly into them. This trial will test sequential escalating doses of PH-762 to evaluate its safety and effectiveness. The treatment aims to boost the body's immune system to fight cancer cells more effectively. Overall, early signs are promising for its potential to manage skin cancers. ^{1 2 3 4 5}

Who Is on the Research Team?

Linda Mahoney

Principal Investigator

Phio Pharmaceuticals Inc.

Are You a Good Fit for This Trial?

This trial is for adults with certain skin cancers: squamous cell carcinoma, melanoma, or Merkel cell carcinoma. They must have at least one tumor between 1 and 3 cm that can be injected and removed surgically. People with other recent cancers, current cancer treatments, serious medical conditions like auto-immune diseases, or who are pregnant/breastfeeding cannot join.

Inclusion Criteria

I have been diagnosed with a specific type of skin cancer.

I have a tumor between 1.0 cm and 3.0 cm that can be reached for treatment.

Exclusion Criteria

I have not had any other cancer in the last 3 years, with some exceptions.

I do not have any serious illnesses that could worsen by joining this study.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive four intratumoral injections of PH-762 at weekly intervals into a single tumor, followed by surgical removal of the tumor approximately two weeks after the last injection

6 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

11 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PH-762

Trial Overview The trial tests PH-762's safety by giving participants four weekly injections directly into a single tumor on the skin. After these injections, the treated tumor will be surgically removed to study how it responded to PH-762 and what happens to the drug in the body.

How Is the Trial Designed?

Group I: Sequential escalating doses of PH-762. Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Phio Pharmaceuticals Inc.

Lead Sponsor

Trials

2

Recruited

50+

Prosoft Clinical

Collaborator

Trials

9

Recruited

910+

Published Research Related to This Trial

The pH-responsive photosensitizer ZnPc(TAP)4 showed high effectiveness in destroying mouse mammary carcinoma cells at a slightly acidic pH (6.5), which mimics the tumor microenvironment, with an IC50 of 0.20 μM under low light exposure.

In vivo studies demonstrated that this photosensitizer not only effectively ablated tumor cells but also provided clear fluorescence imaging of tumor sites, indicating its potential for targeted cancer treatment and imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phthalocyanine-based photosensitizer with tumor-pH-responsive properties for cancer theranostics. [2020]

Among the tested photosensitizers, dye hematoporphyrin ether (DHE) showed the strongest ability to kill tumor cells in a mouse model of neuroblastoma, indicating its potential as an effective treatment option.

Using liposome carriers for the delivery of porphyrin compounds reduced skin phototoxicity compared to saline, while Rhodamine-123 showed no skin phototoxicity but did not effectively target tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of photosensitizers in saline and liposomes for tumor photodynamic therapy and skin phototoxicity. Davis, RK., Straight, R., Kereszti, Z.[2013]

5-aminolevulinic acid (ALA) has been shown to be effective in treating superficial skin cancers and precancerous conditions, with phase III studies demonstrating its efficacy particularly in actinic keratoses and Bowen's disease, leading to its FDA approval for ALA-PDT in 1999.

ALA can also be used for diagnostic purposes, as it induces protoporphyrin IX in epithelial tumors, allowing for enhanced visualization of tumors through fluorescence imaging, which aids in biopsy and surgical planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy and fluorescence diagnosis of skin cancers. Szeimies, RM., Landthaler, M.[2019]

Hematoporphyrin IX (HpIX) showed significantly higher cellular uptake in T-47D cancer cells at lower pH levels (6.5) compared to normal pH levels, suggesting its potential for targeted cancer therapy.

Other photosensitizers like mTHPP, mTHPC, and TPPS(2a) did not show significant changes in uptake with varying pH, indicating that the pH-dependent uptake mechanism may be specific to HpIX and could enhance its tumor selectivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

pH effects on the cellular uptake of four photosensitizing drugs evaluated for use in photodynamic therapy of cancer. Friberg, EG., Cunderlíková, B., Pettersen, EO., et al.[2019]

In a study using hairless mice, two photosensitizers, Hematoporphyrin derivative (HpD) and m-tetra(hydroxyphenyl) chlorine (m-THPC), were evaluated for their effectiveness in targeting skin carcinomas, showing optimal tumor-to-normal skin ratios of 3.2 for HpD and 2.7 for m-THPC at 72 and 24 hours post-injection, respectively.

The study highlights the potential of fluorescence spectroscopy as a non-invasive method to determine the best timing for photochemotherapy, although further validation through organic extraction and subsequent photodynamic therapy is needed to assess the safety and efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of the maximal carcinoma/normal skin ratio after HpD or m-THPC administration in Hairless mice (SKH-1) by fluorescence spectroscopy. Bossu, E., Padilla-Ybarra, JJ., Notter, D., et al.[2019]

Citations

1. dermatologytimes.com dermatologytimes.com/view/ph-762-demonstrates-safety-and-local-efficacy-in-skin-cancer

PH-762 Demonstrates Safety and Local Efficacy in Skin ... Phio Pharmaceuticals reveals promising results for PH-762, a novel siRNA therapy targeting skin cancer, showcasing effective tumor clearance ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11652358/

Self-delivering RNAi immunotherapeutic PH-762 silences ... Ex vivo analyses revealed that IT mPH-762 depleted PD-1 protein, promoted leukocyte and T cell infiltration, and correlated with tumor control.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06014086

Study Details | NCT06014086 | Intratumoral PH-762 for ... 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 ...

4. finance.yahoo.com finance.yahoo.com/news/phio-pharmaceuticals-announces-positive-pathology-124500175.html

Phio Pharmaceuticals Announces Positive Pathology Results Per the trial's protocol, patients receive four injections of PH-762 at weekly intervals and pathologic response is assessed approximately 5 ...

5. targetedonc.com targetedonc.com/view/safety-committee-backs-ph-762-dose-escalation-in-skin-cancer-trial

Safety Committee Backs PH-762 Dose-Escalation in Skin ... A phase 1b trial is evaluating PH-762 for the treatment of cutaneous squamous cell carcinoma, melanoma and Merkel cell carcinoma.