PHN-010 for Cancer
Recruiting in Palo Alto (17 mi)
+7 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Pheon Therapeutics
Must not be taking: Topoisomerase inhibitors
Disqualifiers: Unstable CNS metastasis, Infections, others
No Placebo Group
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.
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.
+7 more
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.
+5 more
Trial 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
Participant Groups
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).
1Treatment groups
Experimental Treatment
Group I: Phase 1a and Phase 1bExperimental Treatment1 Intervention
PHN-010 is administered intravenously.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
NEXT - San AntonioSan Antonio, TX
AdventHealthOrlando, FL
MD Anderson Cancer CenterHouston, TX
Dana Farber Cancer InstituteBoston, MA
More Trial Locations
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Who Is Running the Clinical Trial?
Pheon TherapeuticsLead Sponsor
References
Ku80-Targeted pH-Sensitive Peptide-PNA Conjugates Are Tumor Selective and Sensitize Cancer Cells to Ionizing Radiation. [2021]The development of therapeutic agents that specifically target cancer cells while sparing healthy tissue could be used to enhance the efficacy of cancer therapy without increasing its toxicity. Specific targeting of cancer cells can be achieved through the use of pH-low insertion peptides (pHLIP), which take advantage of the acidity of the tumor microenvironment to deliver cargoes selectively to tumor cells. We developed a pHLIP-peptide nucleic acid (PNA) conjugate as an antisense reagent to reduce expression of the otherwise undruggable DNA double-strand break repair factor, KU80, and thereby radiosensitize tumor cells. Increased antisense activity of the pHLIP-PNA conjugate was achieved by partial mini-PEG sidechain substitution of the PNA at the gamma position, designated pHLIP-αKu80(γ). We evaluated selective effects of pHLIP-αKu80(γ) in cancer cells in acidic culture conditions as well as in two subcutaneous mouse tumor models. Fluorescently labeled pHLIP-αKu80(γ) delivers specifically to acidic cancer cells and accumulates preferentially in tumors when injected i.v. in mice. Furthermore, pHLIP-αKu80(γ) selectively reduced KU80 expression in cells under acidic conditions and in tumors in vivo. When pHLIP-αKu80(γ) was administered to mice prior to local tumor irradiation, tumor growth was substantially reduced compared with radiation treatment alone. Furthermore, there was no evidence of acute toxicity associated with pHLIP-αKu80(γ) administration to the mice. These results establish pHLIP-αKu80(γ) as a tumor-selective radiosensitizing agent. IMPLICATIONS: This study describes a novel agent, pHLIP-αKu80(γ), which combines PNA antisense and pHLIP technologies to selectively reduce the expression of the DNA repair factor KU80 in tumors and confer tumor-selective radiosensitization.
Targeting the Hypoxic and Acidic Tumor Microenvironment with pH-Sensitive Peptides. [2022]The delivery of cancer therapeutics can be limited by pharmacological issues such as poor bioavailability and high toxicity to healthy tissue. pH-low insertion peptides (pHLIPs) represent a promising tool to overcome these limitations. pHLIPs allow for the selective delivery of agents to tumors on the basis of pH, taking advantage of the acidity of the hypoxic tumor microenvironment. This review article highlights the various applications in which pHLIPs have been utilized for targeting and treating diseases in hypoxic environments, including delivery of small molecule inhibitors, toxins, nucleic acid analogs, fluorescent dyes, and nanoparticles.
Manipulating extracellular tumour pH: an effective target for cancer therapy. [2022]The pH in tumour cells and the tumour microenvironment has played important roles in cancer development and treatment. It was thought that both the extracellular and intracellular pH values in tumours are acidic and lower than in normal cells. However, recent progress in the measurement of pH in tumour tissue has disclosed that the intracellular pH (pHi) of cancer cells is neutral or even mildly alkaline compared to normal tissue cells. This review article has summarized the recent advancement in the measurement pHi and extracellular pH (pHe) in cancer cells, and the effect of pHi and pHe on proliferation, migration and biological functions of cancer cells. This paper has also elaborated recent treatment strategies to manipulate pHi and pHe for cancer treatment. Based on the recent progress in pHi and pHe manipulation in cancer treatment, we have proposed potential nanoparticle-based strategies to manipulate pHi and pHe to effectively treat cancer.
Tumor specifically internalizing peptide 'HN-1': Targeting the putative receptor retinoblastoma-regulated discoidin domain receptor 1 involved in metastasis. [2022]Label="BACKGROUND" NlmCategory="BACKGROUND">Less than 0.5% of intravenously injected drugs reach tumors, contributing to side effects. To limit damage to healthy cells, various delivery vectors have been formulated; yet, previously developed vectors suffer from poor penetration into solid tumors. This issue was resolved by the discovery of HN-1 peptide isolated via biopanning a phage-display library. HN-1 targets human head and neck squamous cell carcinoma (HNSCC) (breast, thyroid; potentially lung, cervix, uterine, colon cancer), translocates across the cell membrane, and efficiently infiltrates solid tumors. HN-1 peptide has been conjugated to various anticancer drugs and imaging agents though the identity of its receptor remained enigmatic.
Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP(®) Peptides) Conjugated with Different Fluorescent Dyes. [2019]Acidification of extracellular space promotes tumor development, progression, and invasiveness. pH (low) insertion peptides (pHLIP(®) peptides) belong to the class of pH-sensitive membrane peptides, which target acidic tumors and deliver imaging and/or therapeutic agents to cancer cells within tumors.