A Phase 1/2, Open-label Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of AP402 in HER2-Positive Patients With Locally or Advanced Solid Tumors

AP Biosciences Inc.3 sites in 1 country85 target enrollmentApril 22, 2025

ConditionsAdvanced Solid Tumor

InterventionsAP402 (Part 1 Dose esclation)AP402 (Part 2 Dose Expansion)

DrugsAP402 (Part 1 Dose esclation)AP402 (Part 2 Dose Expansion)

Overview

Phase: Phase 1
Intervention: AP402 (Part 1 Dose esclation)
Conditions: Advanced Solid Tumor
Sponsor: AP Biosciences Inc.
Enrollment: 85
Locations: 3
Primary Endpoint: Estimate of Maximum tolerated dose (MTD)
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase 1/2, multi-regional, multi-center, open-label, first-in-human (FIH), dose-escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary clinical activity of AP402 in HER2-positive patients with locally or advanced solid tumors.

Detailed Description

The study will consist of 2 parts: * Part 1 (Dose Escalation): Dose escalation will consist of 7 cohorts where an IV infusion of AP402 will be administered once every 2 weeks to determine the maximum tolerated dose (MTD) (ie, the highest safe dose administered to patients) and the recommended phase 2 dose (RP2D) of AP402. For dose-escalation, an accelerated dose titration design will be utilized for the first 2 dose cohorts, followed by a standard 3+3 dose titration design for the remaining 5 cohorts. Up to 42 patients will be enrolled in Part 1. * Part 2 (Dose Expansion): After the MTD and/or RP2D are determined by the Safety Review Committee (SRC) (see Section 6.5), additional patients will be enrolled in Part 2 and will be treated with AP402 at that dose once every 2 weeks. Part 2 will be based on the Simon's two-stage optimal design (Simon, 1989) and is expected to enroll approximately 43 patients in 1 or 2 selected tumor types. Administration of the IP will continue for 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, intolerable toxicity, withdrawal of consent, study completion, death or other reasons leading to treatment discontinuation, whichever comes first

Registry

clinicaltrials.gov

Start Date

April 22, 2025

End Date

December 1, 2027

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

AP Biosciences Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients with histologically or cytologically proven locally unresectable advanced or metastatic HER2-postive solid tumors which no standard therapy suitable.
•Adult patients aged ≥ 18 years at the time of signing informed consent form (ICF).
•Written informed consent by the patients or the patient's legally authorized representative prior to Screening.
•Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at study enrollment and an estimated life expectancy of at least 3 months.
•Disease must have at least 1 measurable (long diameter ≥ 1cm) lesion by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.
•Tumor lesions situated in a previously irradiated area are not considered assessable unless there has been demonstrated progression in the lesion. Imaging tests outside the screening period are valid if performed not more than 2 weeks before consent signature and otherwise fulfil protocol criteria.
•Patients with adequate organ function defined by the following:
•Absolute neutrophil count ≥ 1.5 × 109 /L.
•Platelet count ≥ 100 × 109 /L.
•Hemoglobin ≥ 9 g/dL.

Exclusion Criteria

•Patients who have received concurrent antitumor treatment or investigational products within 28 days or 5 half-lives before the start of IP, whichever comes earlier. The antitumor treatments include chemotherapy, radiotherapy (with the exception of palliative bone directed radiotherapy), immunotherapy, targeted therapy, hormonal therapy, or cytokine therapy except for erythropoietin.
•Patients who had received CD137-targeted therapeutics within 28 days or 5 half-lives before the start of IP, whichever comes earlier.
•Patients who had major surgery within 28 days before the start of IP (excluding prior diagnostic biopsy).
•Patients who had continuance of toxicities due to prior antitumor agents that have not resolved to Grade ≤ 1 per NCI CTCAE version 5.0, except alopecia, and\< Grade 2 sensory neuropathy.
•Patients with a history of immune mediated AE of any grade that resulted in discontinuation of prior immunotherapy.
•Patients with previous malignant disease other than the target malignancy to be investigated in this study within the last 2 years with the exception of resected basal or squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix or breast.
•Patients with active leptomeningeal disease or uncontrolled, untreated brain metastasis. Patients with a history of treated and, at the time of Screening, stable central nervous system (CNS) metastases are eligible, provided they meet all the following:
•Brain imaging at Screening shows no evidence of interim progression, patient is clinically stable for at least 2 weeks and without evidence of new brain metastases.
•Measurable disease outside the CNS.
•No ongoing requirement for corticosteroids as therapy for CNS disease; off steroids 2 weeks before the first dose of AP402; anticonvulsants at a stable dose are allowed.

Arms & Interventions

Part 1 (Dose escalation)

Intervention: AP402 (Part 1 Dose esclation)

Part 2 (Dose Expansion)

Intervention: AP402 (Part 2 Dose Expansion)