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

PEEL Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: PEEL-224

Study type: Interventional

Funder types: Industry

Identifiers

NCT05329103

PEEL-224-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 42 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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42 participants in 2 patient groups

PEEL-224 Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: PEEL-224

PEEL-224 Dose Confirmation

Experimental group

Description:

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

Treatment:

Drug: PEEL-224