Phase 1 Clinical Trial to Evaluate the Safety and Anti-Tumor Activity of AB-201

A Multicenter, Open-label, Phase 1 Clinical Trial to Evaluate the Safety and Anti-Tumor Activity of AB-201 in Subjects With Advanced Human Epidermal Growth Factor Receptor 2 Positive(HER2+) Solid Tumors

This clinical trial will enroll subjects with HER2+ solid tumors and is conducted in two phases, which are phase 1a and phase 1b. The primary objective of phase 1 is to determine the safety and tolerability of AB-201 in subjects with advanced HER2+ solid tumors.

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer; Gastric Cancer; Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: AB-201

Detailed Description

This is a Phase 1, multicenter study designed to evaluate the safety, tolerability, and efficacy of AB-201 in subjects with advanced HER2+ solid tumors (specifically, breast and gastric/GEJ cancers).

The Phase 1 will be conducted in two parts, an initial dose escalation stage followed by a dose expansion stage.

Study participation for each subject begins with up to 28 days (1 month) of screening following written informed consent, then lymphodepletion treatment, followed by AB-201. Up to 3 doses of AB-201 may be administered. All subjects will be monitored for a total duration of 18 months of follow up from the first dose administration of AB-201.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hosptial
    • Melbourne, Victoria, Australia, 3084
      • Austin Hosptial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ECOG performance status 0 to 1.
• Histologically confirmed HER2 expressed breast or gastric/GEJ cancer IHC ≥ 2+ within 6 months prior to study entry.
• Confirmed diagnosis of an advanced/unresectable or metastatic HER2+ breast or gastric/GEJ cancer that is refractory to, or intolerable of standard treatment, or for which no standard treatment is available.
• Must have received prior cancer therapy: Subjects with breast cancer must have received ≥ 3 prior systemic therapies; subjects with gastric/GEJ cancer must have received ≥ 2 prior systemic therapy(ies); subjects with IHC 3+ or IHC 2+/ISH+ cancers must have received previous treatment with a HER2-targeting therapy.

Exclusion Criteria:

• Known past or current malignancy other than inclusion diagnosis.
• Known clinically significant cardiac disease.
• Active central nervous system (CNS) metastases, or involvement of the CNS, unless there is a history of at least 3 months of sustained remission.
• Unresolved toxicities from prior anticancer therapy.
• Ongoing uncontrolled systemic infections requiring antibiotic, anti-fungal, or anti-viral therapy.
• History of sensitivity or intolerance to cyclophosphamide or fludarabine.
• Currently Pregnant or lactating
• Severe disease progression or health deterioration within 2 weeks prior to lymphodepletion regimen.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a Dose Escalation; Dose Escalation of AB-201 in advanced metastatic breast cancer, gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression; Interventions:Drug: AB-201Drug: CyclophosphamideDrug: Fludarabine	Drug: Cyclophosphamide; Lymphodepleting chemotherapy; Drug: Fludarabine; Lymphodepleting chemotherapy; Drug: AB-201; NK Cell Therapy
Experimental: Phase 1b Dose Expansion; Dose Confirmation of AB-201 in advanced metastatic breast cancer, gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression; Interventions:Drug: AB-201Drug: CyclophosphamideDrug: Fludarabine	Drug: Cyclophosphamide; Lymphodepleting chemotherapy; Drug: Fludarabine; Lymphodepleting chemotherapy; Drug: AB-201; NK Cell Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, severity, seriousness, and dose relationship of Adverse Events [Safety & Tolerability]	Adverse events and laboratory abnormalities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.	up to 18 months per patient
Determination of Recommended Phase 2 Dose (RP2D)	Assessment of Dose-Limiting Toxicities(DLTs), pharmacokinetics (PK), safety, and objective response rate (ORR) per the Response Evaluation Criteria for Solid Tumors (RECIST) v1.1 in subjects with HER2+ breast cancer and gastric/GEJ cancer. PK: Monitor persistence of AB-201 in subjects samples collected prior to and following AB-201 administration.	up to 18 months per patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the preliminary efficacy, by the objective response rate (ORR) per the Response Evaluation Criteria for Solid Tumors (RECIST) v1.1, of AB-201 in subjects with advanced HER2+ solid tumors	The proportion of subjects who experienced an PR or CR, as assessed by investigators per RECIST v1.1.	up to 18 months per patient

Collaborators and Investigators

• Sponsor: GC Cell Corporation

Study record dates

Study Major Dates

• Study Start (Estimated): October 31, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: March 14, 2024
• First Submitted That Met QC Criteria: March 26, 2024
• First Posted (Actual): April 2, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 22, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: AB-201-01; 103300 (HREC 233/23) (Other Identifier: TGA (Australia))

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