PEEL-224 + Vincristine + Temozolomide for Pediatric Cancer

(PEEL-224 Trial)

Overseen By James Robinson, MSW, MPH

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Theodore Laetsch

Must not be taking: Anti-cancer agents

Disqualifiers: CNS tumors, Transplantation, HIV, others

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

Compensation: Varies

Number of Visits: 3

59 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called PEEL-224 for children and young adults with certain difficult-to-treat cancers, such as neuroblastoma and rhabdomyosarcoma. The researchers aim to determine the optimal dose and evaluate the treatment's effectiveness, both alone and in combination with other drugs, vincristine and temozolomide (a chemotherapy drug). The trial suits those who have tried other treatments but whose cancer persists or worsens. Participants should have a solid tumor diagnosis outside the brain and, if possible, provide a tumor sample. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop all current medications, but there are specific 'washout' periods (time without taking certain medications) for some treatments like chemotherapy, targeted therapy, and others. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that PEEL-224, both alone and combined with vincristine and temozolomide, is under evaluation for safety in children with hard-to-treat cancers. Early results indicate a focus on its safety and patient tolerance.

So far, patients have generally tolerated the treatment well, but studies continue to fully understand any possible side effects. The combination with vincristine and temozolomide aims to improve treatment outcomes, with safety as a top priority.

Since the trial is in its early stages, the main goal is to determine safe dosage levels and closely monitor patient reactions. Any side effects will be carefully tracked and managed. For those considering participation, these trials are designed to prioritize patient safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PEEL-224 because it offers a fresh approach to treating pediatric cancers that have stopped responding to current therapies. Unlike traditional treatments like chemotherapy, which often target rapidly dividing cells, PEEL-224 works by a unique mechanism that could potentially enhance its effectiveness against relapsed or resistant tumors. This novel approach, especially when combined with vincristine and temozolomide, might provide a new hope for children whose cancers have not responded to existing treatments.

What evidence suggests that this trial's treatments could be effective for pediatric cancer?

Research has shown that PEEL-224 damages the DNA of cancer cells, potentially killing them or slowing their growth. This makes it a promising treatment for solid tumors. In this trial, some participants will receive PEEL-224 alone, while others will receive it in combination with vincristine and temozolomide. Studies have found that PEEL-224, whether used alone or with these drugs, could help treat tumors unresponsive to other treatments. Vincristine and temozolomide are already effective against certain cancers. Combining them with PEEL-224 aims to enhance their effects, particularly for challenging cases in children with neuroblastoma (a cancer that starts in young nerve cells) and rhabdomyosarcoma (a cancer of soft tissue). Early signs suggest this approach may offer a new option for children with hard-to-treat cancers. ^{1 5 6 7 8}

Who Is on the Research Team?

Jacquelyn Crane, MD

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for children with specific types of cancer that have not responded to previous treatments or have come back after treatment. These cancers include neuroblastoma and rhabdomyosarcoma, which are serious conditions affecting nerve cells and muscles.

Inclusion Criteria

My cancer can be measured or evaluated by medical tests.

Parental/guardian permission and child assent

My blood tests show my bone marrow is working well.

Exclusion Criteria

Pregnant or lactating females

I am not using any other cancer treatments.

I have previously been treated with PEEL-224.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1A Treatment

Participants receive PEEL-224 as a single agent to test safety, tolerability, and PK profile

21-day cycles, up to 24 cycles (approximately 18 months)

Visits on days 1 and 8 of each cycle

Phase 1B Treatment

Participants receive PEEL-224 in combination with vincristine and temozolomide to test safety, tolerability, and PK profile

21-day cycles, up to 24 cycles (approximately 18 months)

Visits on days 1 and 8 of each cycle

Phase 2 Treatment

Participants receive the RP2D of PEEL-224 in combination with vincristine and temozolomide to estimate objective response rate

21-day cycles, up to 24 cycles (approximately 18 months)

Visits on days 1 and 8 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• PEEL-224
• Temozolomide
• Vincristine

Trial Overview The study is testing PEEL-224 alone (phase 1A) and combined with vincristine and temozolomide (phase 1B). The goal is to find the safest dose for kids (phase 1) and then see how well it works at that dose in shrinking their tumors (phase 2).

How Is the Trial Designed?

Group I: PEEL-224, Vincristine, and Temozolomide Experimental Treatment 3 Interventions

Phase 1B will test the safety, tolerability and pharmacokinetic profile of PEEL-224 in combination with vincristine and temozolomide in pediatric subjects with refractory, progressive and relapsed solid tumors. Phase 2 will preliminary evaluate the activity profile of PEEL-224 in combination with vincristine and temozolomide in pediatric patients with refractory, progressive and relapsed NBL and RMS.

Group II: PEEL-224 Experimental Treatment 1 Intervention

Phase 1A will test the safety, tolerability and PK profile of PEEL-224 as a single agent in pediatric patients with refractory, progressive and relapsed solid tumors.

Who Is Running the Clinical Trial?

Theodore Laetsch

Lead Sponsor

Trials

4

Recruited

80+

Peel Therapeutics Inc

Industry Sponsor

Trials

3

Recruited

160+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06721689

Study Details | NCT06721689 | PEEL-224, Vincristine and ... Phase 1A will test the safety, tolerability and PK profile of PEEL-224 as a single agent in pediatric patients with refractory, progressive and relapsed solid ...

2. cancer.gov cancer.gov/clinicaltrials/NCI-2025-06057

PEEL-224 Alone and in Combination with Vincristine ... It works by damaging the cell's DNA and may kill tumor cells and slow down or stop tumor growth. Giving PEEL-224 alone and in combination with vincristine and ...

3. chop.edu chop.edu/research-studies/peel-224-solid-tumors

PEEL-224 in Solid Tumors The purpose of this study is to find out whether a drug called PEEL-224 ("the study drug") is safe and effective when given as monotherapy.

4. trialx.com trialx.com/clinical-trials/listings/321604/peel-224-vincristine-and-temozolomide-in-pediatric-solid-tumors/

PEEL-224, Vincristine and Temozolomide in Pediatric Solid ... PEEL-224 will be a multi-institutional study conducted at pediatric cancer centers. Phase 1 will enroll approximately 24 subjects (maximum of 12 evaluable ...

5. 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 ... PEEL-224's modified TOP1 inhibitor payload and unique delivery system may offer clinical advantages to patients with solid tumors. On Nov. 2, Dr ...

6. research.chop.edu research.chop.edu/peel-224-in-solid-tumors

PEEL-224 in Solid Tumors | CHOP Research Institute The purpose of this study is to find out whether a drug called PEEL-224 ("the study drug") is safe and effective when given as monotherapy.

7. 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 activity ...

8. trials.braintumor.org trials.braintumor.org/trials/NCT06709495

Phase 1/2 Trial to Evaluate the Safety and Efficacy of PEEL ... The U.S. Food and Drug Administration (FDA) has not approved PEEL-224 as a treatment for Relapsed or Refractory Sarcoma. The U.S. Food and Drug ...