A Study to Evaluate PEEL-224 in Patients With Advanced Solid Tumors

An Early Phase Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of PEEL-224 in Patients With Advanced Solid Tumors

This is a first-in-human, dose escalation, repeat-dose, multi-center, open-label study evaluating safety, tolerability, PK, and preliminary antitumor activity of PEEL-224 in patients with advanced solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: PEEL-224; Drug: FOLF+B

Detailed Description

This is a first-in-human, dose escalation, repeat-dose, multi-center, open-label study evaluating safety, tolerability, PK, and preliminary antitumor activity of a novel topoisomerase I inhibitor (PEEL-224) in patients with advanced solid tumors. Dose escalation will be guided by the modified toxicity probability interval-2 (mTPI-2) design with a target toxicity rate of 25% and an acceptable DLT interval of 20% to 30%. Cohorts of 2 or more patients will be sequentially enrolled at progressively higher dose levels of PEEL-224. For each dose level, all patients must complete Cycle 1 before the decision to dose escalate the next cohort of patients is made.

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Recruiting
      • HonorHealth Research Institiute
      • Contact: Oncology Nurse Navigator; Phone Number: 480-323-1364; Email: clinicaltrials@honorhealth.com
      • Principal Investigator: Erkut Borazanci, MD
  • California
    • Palo Alto, California, United States, 94305
      • Active, not recruiting
      • Stanford Cancer Center
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Completed
      • Carolina BioOncology Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19106
      • Completed
      • Abramson Cancer Center at Pennsylvania Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Rhode Island Hospital
      • Principal Investigator: Howard Safran, MD
      • Contact: Stephan Sando; Phone Number: 401-606-6602; Email: ssando@brownhealth.org
  • Texas
    • Dallas, Texas, United States, 75230
      • Completed
      • Mary Crowley Cancer Research
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • Huntsman Cancer Institute, University of Utah
      • Contact: Susan Sharry, CCRP; Phone Number: 801-587-4488; Email: susan.sharry@hci.utah.edu
      • Principal Investigator: Vaia Florou, MD
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Virginia
      • Principal Investigator: Alexander Spira, MD, PhD, FACP
      • Contact: Malaika Komtangi; Phone Number: 210-580-9500; Email: mkomtangi@nextoncology.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Have a diagnosis of colorectal cancer confirmed by local pathology review (histology or cytology) - Part 2 only
• ECOG of 0 or 1
• Have a diagnosis of advanced or metastatic solid tumor that has progressed after prior standard therapy, have been intolerant or ineligible for standard therapy, or have a malignancy for which there is no approved therapy considered standard of care
• Have at least 1 documented measurable lesion as detected by radiological methods at study entry as per Response Evaluation Criteria in Solid Tumors v1.1
• Have adequate bone marrow reserve
• Have adequate liver function
• Have adequate renal function
• Have completed prior anticancer therapy, including investigational agents, ≥28 days or 5 half lives, whichever is shorter, prior to study treatment
• Have resolution of any clinically significant toxic effects of prior therapy

Exclusion criteria:

• Have primary central nervous system tumors
• Have brain or spinal metastases, except if treated by surgery, surgery plus focal radiotherapy, or radiotherapy alone, with no evidence of progression or hemorrhage ≤14 days prior to the first dose of PEEL-224. Have craniospinal radiotherapy ≤12 weeks prior to the first dose of PEEL-224
• Have significant abnormalities in the level of serum electrolytes
• Have received neutrophil growth factor support ≤14 days prior to the first dose of PEEL 224
• Have an active infection ≤14 days prior to the first dose of PEEL-224
• Use of strong cytochrome P450 (CYP)1A2 and CYP3A4 inhibitors and/or inducers ≤14 days prior to the first dose of PEEL-224 or during the study
• Use of systemic corticosteroids ≤14 days prior to the first dose of PEEL-224
• Are known to be HIV-positive, unless CD4 + lymphocyte count ≥ 300/μL, undetectable viral load; AND Receiving anti-retroviral therapy.
• Have uncontrolled hepatitis B infection or hepatitis C infection;
• Are pregnant or lactating, plan to become pregnant, or plan to donate gametes (ova or sperm) for in vitro fertilization during the study period or for 90 days after the patient's last study-related visit (for eligible patients only, if applicable). Eligible female patients unwilling to employ appropriate contraceptive measures to ensure that pregnancy does not occur during the study will be excluded;
• Have evidence of another malignancy ≤2 years prior to screening (except in situ non melanoma skin cell cancers and in situ cervical carcinoma);
• Are currently enrolled in another therapeutic clinical study or a non-therapeutic clinical study that will conflict with scheduled visits required by this study;
• Have clinically significant, uncontrolled cardiovascular disease
• Have history of cerebrovascular accident, transient ischemic attack, or thrombosis requiring treatment ≤3 months prior to the first dose of PEEL-224
• Have received or will receive a live vaccine ≤14 days prior to the first dose of PEEL 224.
• Have tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection ≤14 days of the Screening Visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1A: PEEL-224 Dose Escalation; 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.	Drug: PEEL-224; Lyophilized powder reconstituted with D5W
Experimental: Part 1B: PEEL-224 Dose Confirmation; PEEL-224 is administered intravenously (IV) on Days 1 and 15 of a 28-day cycle at the dose determined in Part 1A	Drug: PEEL-224; Lyophilized powder reconstituted with D5W
Experimental: Part 2: PEEL-224 plus FOLF+B; 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.	Drug: PEEL-224; Lyophilized powder reconstituted with D5W; Drug: FOLF+B; infusional 5-FU, LV, and bevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine maximum tolerated dose	Frequency, severity, and relatedness of dose limiting toxicities	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall safety and tolerability of PEEL-224	Frequency, severity, and relatedness of AEs and SAEs	through study completion, expected average of 6 months
Antitumor activity assessment	based on RECIST 1.1	every 8 weeks through study completion, expected average of 6 months
Cmax of PEEL-224 and its metabolite	maximum blood concentration of PEEL-224 and its metabolite	Through 96 hours after dosing on Cycle 1 Day 1 and through 168 hours hours of dosing on Cycle 1 Day 15
Tmax of PEEL-224 and its metabolite	Time to maximum blood concentration of PEEL-224 and its metabolite	Through 96 hours after dosing on Cycle 1 Day 1 and through 168 hours hours of dosing on Cycle 1 Day 15
changes in QTcF/QTcBBB	ECG parameter readings	Through Cycle 1 (28 days)

Collaborators and Investigators

• Sponsor: Peel Therapeutics Inc

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: March 31, 2022
• First Submitted That Met QC Criteria: April 8, 2022
• First Posted (Actual): April 14, 2022

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: PEEL-224-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No