PEEL-224 for Cancer

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Peel Therapeutics Inc

Must not be taking: CYP inhibitors, Corticosteroids

Disqualifiers: CNS tumors, Brain metastases, Cardiovascular, others

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

Compensation: Varies

Number of Visits: Unknown

65 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called PEEL-224 to determine its safety and effectiveness for people with advanced cancers unresponsive to standard treatments. The study begins by identifying the optimal dose of PEEL-224, then tests this dose alone and with other drugs. It seeks participants with advanced or metastatic solid tumors that have worsened after previous treatments. As a Phase 1 trial, the research focuses on understanding how the treatment 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 requires that you stop using certain medications, like strong CYP1A2 and CYP3A4 inhibitors or inducers, and systemic corticosteroids, at least 14 days before starting the study. It's best to discuss your current medications with the trial team to see if any need to be stopped.

Is there any evidence suggesting that PEEL-224 is likely to be safe for humans?

Research has shown that PEEL-224 is being tested for safety and tolerance in humans. In other studies, PEEL-224 has been combined with drugs like vincristine and temozolomide, focusing on safety. It's important to note that PEEL-224 is just beginning human trials, so safety information remains limited.

This is a Phase 1 trial, indicating that PEEL-224 is in the early testing stages. The primary goal is to assess its safety for people. This process typically starts with low doses, gradually increasing to determine the safest and most effective amount.

As this is a Phase 1 trial, researchers are still gathering safety data. This stage is crucial for identifying any side effects or unwanted reactions. In early trials, researchers closely monitor participants for any issues. So far, the available data has not reported major safety concerns.

In summary, while PEEL-224 is under safety testing and monitoring, more information will emerge as the trial progresses. Participants receive detailed information about potential risks and benefits to help them make informed decisions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about PEEL-224 for cancer treatment because it offers a different approach compared to standard chemotherapy options. Unlike traditional treatments, which often target rapidly dividing cells in general, PEEL-224 is designed to work by a novel mechanism, potentially offering a more targeted impact on cancer cells while possibly reducing side effects. Additionally, PEEL-224 is administered intravenously in a specific cycle that allows for adaptable dosing, which could lead to better individualized treatment plans. This innovative approach may enhance treatment efficacy and improve patient outcomes.

What evidence suggests that PEEL-224 could be an effective treatment for cancer?

Research has shown that PEEL-224 could be a promising cancer treatment. Studies indicate that when combined with PD-1 inhibitors, PEEL-224 enhances the ability to fight tumors more effectively than when each is used alone. This suggests that PEEL-224 might help the immune system combat tumors. In this trial, researchers are testing PEEL-224 in different contexts: Part 1A involves dose escalation to determine safety and effectiveness for solid tumors, Part 1B confirms the dose, and Part 2 tests PEEL-224 in combination with FOLF+B. Although still in early stages, its mechanism suggests potential benefits for hard-to-treat cancers. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have worsened after standard treatments, or when no standard care exists. Participants must be in good physical condition (ECOG 0 or 1), have measurable tumors, and proper organ function. They can't join if they've used certain drugs recently, have uncontrolled diseases, other cancers within the last 2 years, brain metastases unless treated and stable, are pregnant/breastfeeding, or plan to donate gametes.

Inclusion Criteria

My liver is working well.

I am fully active or can carry out light work.

My kidneys are working well.

Exclusion Criteria

I haven't taken strong drugs that affect liver enzymes in the last 14 days.

My brain or spinal cancer has been treated and hasn't worsened or bled in the last 14 days.

Currently enrolled in another therapeutic clinical study or a non-therapeutic clinical study that will conflict with scheduled visits required by this study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

PEEL-224 is administered intravenously on Days 1, 8, and 15 of a 28-day cycle. Dose escalation will be guided by the mTPI-2 design until a recommended phase 2 dose is determined.

28 days per cycle, multiple cycles

Dose Confirmation

An additional arm of patients will be enrolled to confirm the recommended phase 2 dose.

28 days per cycle, multiple cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments every 8 weeks.

6 months

What Are the Treatments Tested in This Trial?

Interventions

• PEEL-224

Trial Overview

The study tests PEEL-224's safety and effectiveness in treating advanced solid tumors. It's a first-in-human trial where doses will gradually increase to find the right balance between safety and response. The drug's behavior in the body (pharmacokinetics) and its impact on tumor size will also be assessed.

How Is the Trial Designed?

Group I: Part 2: PEEL-224 plus FOLF+B Experimental Treatment 2 Interventions

PEEL-224 is administered intravenously (IV) and in combination with FOLFPB on Days 1 and 15 of a 28-day cycle. Up to 3 dose levels of PEEL-224 will be tested as determined by the results of Part 1.

Group II: Part 1B: PEEL-224 Dose Confirmation Experimental Treatment 1 Intervention

PEEL-224 is administered intravenously (IV) on Days 1 and 15 of a 28-day cycle at the dose determined in Part 1A

Group III: Part 1A: PEEL-224 Dose Escalation Experimental Treatment 1 Intervention

PEEL-224 is administered intravenously (IV) on Days 1, 8, and 15 of a 28-day cycle. The study will begin at a low starting dose and will increase between cohorts according to mTPI-2 until a recommended phase 2 dose is determined. Approximately 10 dose levels are anticipated to be studied.

Who Is Running the Clinical Trial?

Peel Therapeutics Inc

Lead Sponsor

Trials

3

Recruited

160+

Published Research Related to This Trial

VP 16-213, a new semisynthetic epipodophyllotoxin, demonstrated clinically valuable antitumor activity in a phase II trial involving 33 patients with solid tumors and acute leukemias, particularly showing promising results in patients with oat cell carcinoma of the lung.

The drug was generally well tolerated, but it commonly caused side effects like leukothrombopenia and hair loss, indicating a need for further studies to optimize its dosage and explore its use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic experiences using the new podophyllotoxin derivative VP 16-213 in malignant human tumors]. Jungi, WF., Senn, HJ., Beckmann, C., et al.[2013]

The modified chimeric Pseudomonas exotoxin, PEdelta53L/TGF-alpha/KDEL, significantly increases the sensitivity of human tumors to radiation therapy by lowering the apoptotic threshold in tumor cells lacking functional p53, suggesting a new approach to overcome resistance to apoptosis.

Importantly, this treatment did not result in increased local or systemic toxicity, indicating a favorable safety profile while enhancing the effectiveness of radiation therapy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of apoptotic response of a radiation-resistant human carcinoma by Pseudomonas exotoxin-chimeric protein. Seetharam, S., Nodzenski, E., Beckett, MA., et al.[2023]

In a phase I study involving 20 patients with high-risk squamous cell carcinoma of the head and neck, the maximum tolerated dose (MTD) of docetaxel combined with concurrent radiotherapy was determined to be 15 mg/m2, with oral stomatitis identified as the main dose-limiting toxicity.

The treatment was generally well tolerated, and while five patients experienced locoregional relapse after a median follow-up of 32 months, the results suggest that this combination therapy is safe enough to warrant further investigation in a phase II trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I adjuvant radiation with docetaxel in high-risk head and neck cancer. Clark, JI., Eisner, RM., Hofmeister, C., et al.[2021]

VP 16-213, a new drug derived from podophyllotoxin, shows significant effectiveness against small-cell bronchial carcinoma and may also be beneficial for other lung tumors, testicular teratomas, and certain leukemias, making it a promising treatment option.

The drug's mechanism of action is not fully understood, but it appears to cause the most damage to cancer cells during specific phases of the cell cycle, and prolonged administration may enhance its effectiveness compared to single doses, with no long-term toxicity reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Podophyllotoxin derivative VP 16-213. Arnold, AM.[2019]

In a study involving 129 patients with locally advanced epithelial malignancies, high-dose cisplatin (100 mg/m2) combined with radiation showed promising median survival times, particularly for squamous cell carcinoma of the head and neck, which had a median survival of 36 months.

The treatment was administered every 3 weeks during radiation therapy, and while median survival times for ovarian and lung cancers were 19 and 14 months respectively, some cancers like cervical carcinoma and prostate adenocarcinoma have not yet reached median survival, indicating ongoing effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with high-dose cisplatin and radiation for treatment of epithelial malignancies. Coughlin, CT.[2013]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05329103

NCT05329103 | A Study to Evaluate PEEL-224 in Patients ...

This is a first-in-human, dose escalation, repeat-dose, multi-center, open-label study evaluating safety, tolerability, PK, and preliminary antitumor ...

2.

jitc.bmj.com

jitc.bmj.com/content/11/Suppl_1/A507

456 100% complete response to PEEL-224 in combination ...

Our results indicate that combined PEEL-224 and PD-1 inhibition may improve antitumor efficacy over each monotherapy.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06709495

Study Details | NCT06709495 | Phase 1/2 Trial to Evaluate ...

This research is being done to test a new drug called PEEL-224 in combination with two commercially available drugs, Vincristine and Temozolomide.

4.

peeltx.com

peeltx.com/news/peel-therapeutics-closes-new-financing-round-and-expands-board-of-directors-to-support-evolution-based-medicines-for-cancer-and-inflammation/

Peel Therapeutics to Present Data on its TOP1 Inhibitor ...

Based on these findings, PEEL-224 combined with immunotherapy may be a promising approach for difficult-to-treat tumors and translation to human ...

5.

trials.braintumor.org

trials.braintumor.org/trials/NCT06709495

Phase 1/2 Trial to Evaluate the Safety and Efficacy of PEEL ...

- The effects of PEEL-224 in combination with temozolomide and vincristine on the developing human fetus are unknown. For this reason, women of child-bearing ...

6.

aacrjournals.org

aacrjournals.org/mct/article/24/10_Supplement/B001/766264/Abstract-B001-Phase-1-2-trial-to-evaluate-the

Phase 1/2 trial to evaluate the safety and efficacy of PEEL-224 ...

Phase 1/2 trial to evaluate the safety and efficacy of PEEL-224 in combination with vincristine and temozolomide in adolescents and young adults ...

7.

peeltx.com

peeltx.com/news/peel-therapeutics-initiates-clinical-trial-of-peel-224-in-patients-with-advanced-solid-tumors/

PEEL Therapeutics Initiates Clinical Trial of PEEL-224 in ...

The trial will evaluate the safety, tolerability, pharmacokinetics and preliminary antitumor activity of PEEL-224. “Building on millions of ...