ACE1702 in Subjects With Advanced or Metastatic HER2-expressing Solid Tumors

Study Overview
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Brief Summary
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ACE1702 (anti-HER2 oNK cells) is an off-the-shelf Natural Killer (NK) cell product that targets human HER2-expressing solid tumors. The ACE1702-001 phase I study aims to evaluate the safety and tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ACE1702 in patients with advanced or metastatic HER2-expressing tumors, and to determine the phase Ib/II starting dose for ACE1702.

Official Title
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A Phase I, Open Label, Dose Escalation Study of ACE1702 Cell Immunotherapy in Subjects With Advanced or Metastatic HER2-expressing Solid Tumors

Conditions
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Locally Advanced Solid Tumor, Metastatic Cancer, Solid Tumor, HER2-positive Gastric Cancer, HER2-positive Metastatic Breast Cancer

Intervention / Treatment
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* Drug: ACE1702
* Drug: Cyclophosphamide
* Drug: Fludarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Subjects must be ≥ 18 years of age ( ≥ 20 years of age for Taiwan site) Subject with advanced or metastatic solid tumors that is not amenable to surgical resection and is not eligible or has refused other approved therapeutic options that have demonstrated clinical benefit. Histologically confirmed HER2 expression. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 Measurable or non-measurable evaluable disease according to RECIST 1.1 Adequate hematologic and end-organ function at baseline Oxygen saturation via pulse oxygenation ≥ 90% at rest on room air Exclusion Criteria: Untreated central nervous system (CNS) metastases Multiple primary malignancies Clinically significant cardiovascular disease such as New York Heart Association (NYHA) cardiac disease (class III or greater) Pregnant or lactating female Serious, uncontrolled medical disorder that, in the opinion of the Investigator, would impair the ability of the subject to receive study treatment History of autoimmune or immune mediated symptomatic disease Any anti-cancer chemotherapy or targeted small molecule therapy, or experimental therapy/device within 4 weeks or 5 half-lives of the drug prior to planned start of the study

Ages Eligible for Study
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Minimum Age: 18 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: ACE1702 Dose Level 1<br>Lympho-conditioning agents followed by ACE1702 (anti-HER2 oNK cells) will be administered to patients with advanced or metastatic, HER2-expressing solid tumors. HER2 expressing is defined has having HER2 immunohistochemistry (IHC) 2+ or above. Dose Level: 1 Planned number of subjects: 1 to 6 | Drug: ACE1702<br>* ACE1702 cellular therapy (anti-HER2 oNK cells) given intravenously<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>|
| Experimental: ACE1702 Dose Level 2<br>Lympho-conditioning agents followed by ACE1702 (anti-HER2 oNK cells) will be administered to patients with advanced or metastatic, HER2-expressing solid tumors. HER2 expressing is defined has having HER2 IHC 2+ or above. Dose Level: 2 Planned number of subjects: 1 to 6 | Drug: ACE1702<br>* ACE1702 cellular therapy (anti-HER2 oNK cells) given intravenously<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>|
| Experimental: ACE1702 Dose Level 3<br>Lympho-conditioning agents followed by ACE1702 (anti-HER2 oNK cells) will be administered to patients with advanced or metastatic, HER2-expressing solid tumors. HER2 expressing is defined has having HER2 IHC 2+ or above. Dose Level: 3 Planned number of subjects: 3 to 6 | Drug: ACE1702<br>* ACE1702 cellular therapy (anti-HER2 oNK cells) given intravenously<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>|
| Experimental: ACE1702 Dose Level 4<br>Lympho-conditioning agents followed by ACE1702 (anti-HER2 oNK cells) will be administered to patients with advanced or metastatic, HER2-expressing solid tumors. HER2 expressing is defined has having HER2 IHC 2+ or above. Dose Level: 4 Planned number of subjects: 3 to 6 | Drug: ACE1702<br>* ACE1702 cellular therapy (anti-HER2 oNK cells) given intravenously<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>|
| Experimental: ACE1702 Dose Level 5<br>Lympho-conditioning agents followed by ACE1702 (anti-HER2 oNK cells) will be administered to patients with advanced or metastatic, HER2-expressing solid tumors. HER2 expressing is defined has having HER2 IHC 2+ or above. Dose Level: 5 Planned number of subjects: 3 to 6 | Drug: ACE1702<br>* ACE1702 cellular therapy (anti-HER2 oNK cells) given intravenously<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>|
| Experimental: ACE1702 Dose 6<br>Lympho-conditioning agents followed by ACE1702 (anti-HER2 oNK cells) will be administered to patients with advanced or metastatic, HER2-expressing solid tumors. HER2 expressing is defined has having HER2 IHC 2+ or above. Dose Level: 6 Planned number of subjects: 3 to 6 | Drug: ACE1702<br>* ACE1702 cellular therapy (anti-HER2 oNK cells) given intravenously<br>Drug: Cyclophosphamide<br>* Lympho-conditioning agent<br>Drug: Fludarabine<br>* Lympho-conditioning agent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events, including Dose Limiting Toxicities (DLTs) and Serious Adverse Events (SAEs) | Number of subjects experiencing adverse events, and the frequency and severity of adverse events. Endpoint for determining the Maximum Tolerated Dose (MTD). If MTD is not identified, the highest dose administered becomes the Maximum Administered Dose (MAD). | Day 7 through Day 28 / Day 4 through Day 25 | 
| Phase Ib/II starting dose for ACE1702 | The recommended phase Ib/II starting dose based on MTD. If MTD is not reached, then the recommended phase Ib/II dose will be determined based on the MAD, safety data, and pharmacodynamics data. | Through study completion, up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantify NK cell persistence after administering ACE1702 | Duration of ACE1702 persistence | Day 21 | 
| Evaluate immune function after administering ACE1702 | Measurement of serum cytokine levels, pg/mL (Interferon-γ, TNF-α, IL-2, IL-6, IL-8 and IL-10) at set timepoints | Day 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NK Cell Therapy, Cellular Therapy, Breast Cancer, Gastric Cancer, Ovarian Cancer, Endometrial Cancer, Metastatic Cancer, Colorectal Cancer, Head and Neck Cancer, Pancreatic Cancer, Bladder Cancer, Non-small-cell Lung Carcinoma