PHN-010 for Cancer

Recruiting at 7 trial locations

Overseen By Myles Clancy

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pheon Therapeutics

Must not be taking: Topoisomerase inhibitors

Disqualifiers: Unstable CNS metastasis, Infections, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

273 Participants Needed

Trial Summary

What is the purpose of this trial?

This first-in-human study will evaluate safety, tolerability, anti-tumor activity, immunogenicity, pharmacokinetics and pharmacodynamics of PHN-010, a novel antibody-drug conjugate (ADC), in patients with advanced solid tumors.

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 have received systemic anti-cancer therapy within a certain period before starting the study drug. It's best to discuss your specific medications with the trial team.

How is the drug PHN-010 different from other cancer treatments?

PHN-010 is unique because it targets the acidic environment of tumors, using a peptide that can penetrate solid tumors and deliver treatment directly to cancer cells, potentially reducing side effects on healthy cells. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults with certain advanced solid tumors, including lung, endometrial, ovarian, cervical, and colon cancers. Participants must have had at least one prior therapy and no available standard treatment options or be intolerant to them. They should have a performance status of 0 or 1 (able to carry out daily activities), measurable disease, adequate organ function, and a tumor tissue sample.

Inclusion Criteria

My lung cancer is advanced and has spread to other parts.

I am fully active or can carry out light work.

My organs are working well.

Exclusion Criteria

My cancer has spread to my brain and is not stable.

I haven't taken cancer drugs within the last 21 days or five half-lives, whichever is shorter.

I have not had major surgery in the last 28 days or still have side effects from it.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PHN-010 intravenously to evaluate safety, tolerability, and anti-tumor activity

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• PHN-010

Trial Overview PHN-010 is being tested in this study. It's an antibody-drug conjugate aimed at treating various advanced solid tumors. The trial will assess its safety, how well it's tolerated by patients' bodies, its effectiveness against cancer cells (anti-tumor activity), immune response (immunogenicity), distribution within the body (pharmacokinetics), and effect on the body's biological processes (pharmacodynamics).

Participant Groups

Group I: Phase 1a and Phase 1b Experimental Treatment 1 Intervention

PHN-010 is administered intravenously.

Who Is Running the Clinical Trial?

Pheon Therapeutics

Lead Sponsor

Trials

1

Recruited

270+

Findings from Research

The pHLIP-αKu80(γ) conjugate effectively targets acidic cancer cells, selectively reducing the expression of the DNA repair factor KU80, which enhances the effectiveness of radiation therapy without harming healthy tissue.

In mouse models, pHLIP-αKu80(γ) significantly reduced tumor growth when combined with radiation treatment, and it showed no acute toxicity, indicating its potential as a safe and effective radiosensitizing agent for cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ku80-Targeted pH-Sensitive Peptide-PNA Conjugates Are Tumor Selective and Sensitize Cancer Cells to Ionizing Radiation. Kaplan, AR., Pham, H., Liu, Y., et al.[2021]

pH-low insertion peptides (pHLIPs) can enhance the delivery of cancer treatments by selectively targeting tumors based on their acidic environment, which is common in hypoxic tumors.

This review discusses the versatility of pHLIPs in delivering various therapeutic agents, including small molecule inhibitors and nanoparticles, potentially improving treatment efficacy while reducing toxicity to healthy tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the Hypoxic and Acidic Tumor Microenvironment with pH-Sensitive Peptides. Dharmaratne, NU., Kaplan, AR., Glazer, PM.[2022]

Recent studies reveal that the intracellular pH of cancer cells is often neutral or mildly alkaline, contrary to the previous belief that both intracellular and extracellular pH in tumors are acidic.

The review discusses new treatment strategies that aim to manipulate both intracellular and extracellular pH levels in cancer cells, suggesting that nanoparticle-based approaches could be effective in enhancing cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manipulating extracellular tumour pH: an effective target for cancer therapy. Hao, G., Xu, ZP., Li, L.[2022]

The HN-1 peptide has been identified as a promising delivery vector for anticancer drugs, effectively targeting and infiltrating solid tumors like head and neck squamous cell carcinoma (HNSCC) by binding to the discoidin-domain receptor 1 (DDR1), which is overexpressed in these cancers.

The study provides insights into the mechanism of HN-1's action, showing that it is internalized through energy-dependent clathrin-mediated endocytosis, suggesting that targeting DDR1 could enhance the efficacy of treatments for metastatic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor specifically internalizing peptide 'HN-1': Targeting the putative receptor retinoblastoma-regulated discoidin domain receptor 1 involved in metastasis. Hong, FU., Castro, M., Linse, K.[2022]

pHLIP(®) peptides effectively target acidic tumors, allowing for the delivery of imaging and therapeutic agents, which is crucial for cancer treatment.

Fluorescently labeled pHLIP(®) variants can identify small metastatic lesions in the lungs, demonstrating their potential for precise tumor localization and improved cancer diagnostics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP(®) Peptides) Conjugated with Different Fluorescent Dyes. Adochite, RC., Moshnikova, A., Golijanin, J., et al.[2019]

References

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

Ku80-Targeted pH-Sensitive Peptide-PNA Conjugates Are Tumor Selective and Sensitize Cancer Cells to Ionizing Radiation. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting the Hypoxic and Acidic Tumor Microenvironment with pH-Sensitive Peptides. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Manipulating extracellular tumour pH: an effective target for cancer therapy. [2022]

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

Tumor specifically internalizing peptide 'HN-1': Targeting the putative receptor retinoblastoma-regulated discoidin domain receptor 1 involved in metastasis. [2022]

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

Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP(®) Peptides) Conjugated with Different Fluorescent Dyes. [2019]