A Clinical Trial of the Safety and Anti-Tumor Activity of AB-201 in Subjects With Advanced HER2+ Solid Tumors

Study Overview
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Brief Summary
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This clinical trial will enroll subjects with HER2+ solid tumors and is conducted in two phases. The primary objective of Phase 1 is to determine the safety and tolerability of AB-201 in subjects with advanced HER2+ solid tumors. The primary objective of Phase 2 is to evaluate the efficacy of AB-201. Subjects will receive up to 3 doses of AB-201, followed by scheduled assessments of overall health and tumor response.

Official Title
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A Multicenter, Open-label, Phase 1/2 Clinical Trial to Evaluate the Safety and Anti-Tumor Activity of AB-201 in Subjects With Advanced HER2+ Solid Tumors

Conditions
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Breast Cancer, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma

Intervention / Treatment
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* Drug: AB-201
* Drug: Cyclophosphamide
* Drug: Fludarabine


Participation Criteria
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Eligibility Criteria
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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 ≥ 2 prior systemic therapies; subjects with gastric/GEJ cancer must have received ≥ 1 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. Pregnant or lactating females and subjects of both sexes who are not willing to practice birth control from the time of consent through 6 months after administration of the last AB-201 dose. Severe disease progression or health deterioration within 2 weeks prior to lymphodepletion regimen.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1 Dose Confirmation<br>Dose Confirmation of AB-201 in advanced metastatic breast cancer, gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression | Drug: AB-201<br>* NK Cell Therapy<br>Drug: Cyclophosphamide<br>* Lymphodepleting chemotherapy<br>Drug: Fludarabine<br>* Lymphodepleting chemotherapy<br>|
| Experimental: Phase 2 Cohort A<br>AB-201 given to patients with advanced/unresectable or metastatic breast cancer with HER2 overexpression (IHC ≥2+) that is refractory to or intolerant of standard treatment, or for which no standard treatment is available | Drug: AB-201<br>* NK Cell Therapy<br>Drug: Cyclophosphamide<br>* Lymphodepleting chemotherapy<br>Drug: Fludarabine<br>* Lymphodepleting chemotherapy<br>|
| Experimental: Phase 2 Cohort B<br>AB-201 given to patients with advanced/unresectable or metastatic breast cancer with HER2 overexpression (IHC 3+ or IHC 2+/ISH+) that is relapsed to, refractory to, or intolerant of previous trastuzumab deruxtecan (T-DXd) based therapy | Drug: AB-201<br>* NK Cell Therapy<br>Drug: Cyclophosphamide<br>* Lymphodepleting chemotherapy<br>Drug: Fludarabine<br>* Lymphodepleting chemotherapy<br>|
| Experimental: Phase 2 Cohort C<br>AB-201 given to patients with advanced/unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression (IHC ≥ 2+) that is refractory to or intolerant of standard treatment, or for which no standard treatment is available | Drug: AB-201<br>* NK Cell Therapy<br>Drug: Cyclophosphamide<br>* Lymphodepleting chemotherapy<br>Drug: Fludarabine<br>* Lymphodepleting chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: incidence and severity of adverse events and serious adverse events |  | From the time of consent through End of Study (up to 18 months per patient) | 
| Determination of Recommended Phase 2 Dose (RP2D): safety, preliminary efficacy (based on objective response rate (ORR) defined as the proportion of patients with a complete or partial response) and pharmacokinetics |  | From the time of consent through End of Study (up to 18 months per patient) | 
| Efficacy: Objective Response Rate, defined as the proportion of patients with a complete or partial response |  | From the time of consent through End of Study (up to 18 months per patient) |