A Study of AP402 in HER2-Positive Patients With Locally or Advanced Solid Tumors

NCT06669975 | Recruiting Phase 1 DMC

• 1 other identifier: AP402-101
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 3

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.

Conditions

Advanced Solid Tumor

Keywords

HER2-positive; local solid tumors; advanced solid tumors

Outcome Measures

Primary Outcomes (6)

• Estimate of Maximum tolerated dose (MTD)

  This will be based on dose limiting toxicities (DLT) observed during the DLT evaluation period.

  Baseline to 90 days after the last dose

• Number of participants with Adverse events (AEs) and Serious Adverse events (SAE) as assessed by CTCAE V5

  Baseline to 90 days after the last dose

• To evaluate R2PD based on PK parameters- Cmax (Maximum plasma concentration)

  Baseline to 90 days after the last dose

• To evaluate R2PD based on PK parameters- Tmax (time for maximum concentration)

  Baseline to 90 days after the last dose

• To evaluate R2PD based on PK parameters- AUC (Area under curve)

  Baseline to 90 days after the last dose

• To evaluate R2PD based on PK parameters- T1/2 (terminal half-life)

  Baseline to 90 days after the last dose

Secondary Outcomes (11)

• To evaluate objective response rate (ORR)

  Baseline to 30 days after the last dose

• Number of patients with disease Control Rate (DCR)

  Baseline to 90 days after the last dose

• Number of patients with changes in duration of objective response (DOOR)

  Baseline to 30 days after the last dose

• Duration of disease control response (DODC):

  Baseline to 30 days after the last dose

• To assess progression-free survival (PFS):

  Up to 48 months

Study Arms (2)

Part 1 (Dose escalation)

EXPERIMENTAL

Drug: AP402 (Part 1 Dose esclation)

Part 2 (Dose Expansion)

EXPERIMENTAL

Drug: AP402 (Part 2 Dose Expansion)

Interventions

AP402 (Part 1 Dose esclation) DRUG

Dose escalation will consist of 7 cohorts where an Intraveous 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.

Part 1 (Dose escalation)

AP402 (Part 2 Dose Expansion) DRUG

After the MTD and/or RP2D are determined by the SRC, additional patients will be enrolled in Phase 2 dose expansion and will be treated with AP402 at that dose.

Part 2 (Dose Expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 1.1. 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.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN or \< 5 × ULN if hepatic metastases present.
• Serum total bilirubin ≤ 1.5 × ULN (or \< 3 × ULN for patients with Gilbert's syndrome).
• Alkaline phosphatase ≤ 2.5 × ULN or \< 5 × ULN if bone metastases present.
• Prothrombin time ≤ 1.5 × ULN.
• International normalized ratio (INR) ≤ 2.0 or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. Exception: INR 2 to ≤ 3 is acceptable for patients on a stable dose of anticoagulants.
• Estimated creatinine clearance \> 45 mL/min according to the Cockcroft Gault formula.

You may not qualify if:

• 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.
• Patients who received any organ transplantation including allogeneic stem cell transplantation.
• Patients with significant acute or chronic infections including, among others:
• Infection requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days before first dose of AP402.
• Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Note: An HIV serology test (including antigen and/or antibodies) will be conducted at baseline for the patients with unknown HIV status and patients with positive HIV test will be excluded.

Sponsors & Collaborators

• AP Biosciences Inc.: lead

Study Sites (3)

Macquarie University Clinical Trials Unit

Macquarie, New South Wales, 2109, Australia

NOT YET RECRUITING

Flinders Medical Centre

Bedford Park, South Australia, 5043, Australia

NOT YET RECRUITING

Linear Clinical Research

Perth, Western Australia, 6009, Australia

RECRUITING

Central Study Contacts

Linnea Shen

CONTACT

+886-2-2653-2886; yashen@apbioinc.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2024
• First Posted: November 1, 2024
• Study Start: April 22, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 25, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3)