Intratumoral PH-762 for Skin Cancer

Recruiting at 6 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

Trial Summary

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.

What makes the drug PH-762 unique for treating skin cancer?

PH-762 is unique because it is administered directly into the tumor (intratumoral), which may enhance its effectiveness by targeting the cancer cells more precisely compared to other treatments that are applied systemically or topically. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial tests PH-762 injections in adults with certain skin cancers. The treatment helps the immune system recognize and fight the cancer by stopping it from hiding. Patients will receive injections over a period of weeks.

Research Team

Linda Mahoney

Principal Investigator

Phio Pharmaceuticals Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Photodynamic therapy and fluorescence diagnosis of skin cancers. [2019]

2. Ireland pubmed.ncbi.nlm.nih.gov

pH effects on the cellular uptake of four photosensitizing drugs evaluated for use in photodynamic therapy of cancer. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Comparison of photosensitizers in saline and liposomes for tumor photodynamic therapy and skin phototoxicity. [2013]

4. England 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. [2019]

5. England pubmed.ncbi.nlm.nih.gov

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