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

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

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumor; Metastatic Cancer; HER2-positive Gastric Cancer; HER2-positive Metastatic Breast Cancer; Locally Advanced Solid Tumor
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: ACE1702

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Taipei Veteran General Hospital
• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Univeristy
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACE1702 Dose Level 1; 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: Cyclophosphamide; Lympho-conditioning agent; Drug: Fludarabine; Lympho-conditioning agent; Drug: ACE1702; ACE1702 cellular therapy (anti-HER2 oNK cells) given intravenously
Experimental: ACE1702 Dose Level 2; 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: Cyclophosphamide; Lympho-conditioning agent; Drug: Fludarabine; Lympho-conditioning agent; Drug: ACE1702; ACE1702 cellular therapy (anti-HER2 oNK cells) given intravenously
Experimental: ACE1702 Dose Level 3; 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: Cyclophosphamide; Lympho-conditioning agent; Drug: Fludarabine; Lympho-conditioning agent; Drug: ACE1702; ACE1702 cellular therapy (anti-HER2 oNK cells) given intravenously
Experimental: ACE1702 Dose Level 4; 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: Cyclophosphamide; Lympho-conditioning agent; Drug: Fludarabine; Lympho-conditioning agent; Drug: ACE1702; ACE1702 cellular therapy (anti-HER2 oNK cells) given intravenously
Experimental: ACE1702 Dose Level 5; 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: Cyclophosphamide; Lympho-conditioning agent; Drug: Fludarabine; Lympho-conditioning agent; Drug: ACE1702; ACE1702 cellular therapy (anti-HER2 oNK cells) given intravenously
Experimental: ACE1702 Dose 6; 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: Cyclophosphamide; Lympho-conditioning agent; Drug: Fludarabine; Lympho-conditioning agent; Drug: ACE1702; ACE1702 cellular therapy (anti-HER2 oNK cells) given intravenously

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response using Response Evaluation Criteria In Solid Tumors Assessment (RECIST) version 1.1	Tumor response via radiographic assessments	Day 35 (+7 day window) of each 6 week cycle, up to 24 months
Shift in serum tumor marker values (CA-125, CA 19-9, and CEA levels, in applicable tumor types)	Tumor response via tumor marker assessments (in applicable tumor types)	Day 35 (+7 day window) of each 6 week cycle, up to 24 months

Collaborators and Investigators

• Sponsor: Acepodia Biotech, Inc.
• Investigators: Study Director: Michael Kurman, MD, Acepodia Biotech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2020
• Primary Completion (Actual): July 15, 2024
• Study Completion (Actual): July 15, 2024

Study Registration Dates

• First Submitted: March 18, 2020
• First Submitted That Met QC Criteria: March 22, 2020
• First Posted (Actual): March 24, 2020

Study Record Updates

• Last Update Posted (Actual): December 5, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Breast Cancer; Head and Neck Cancer; Gastric Cancer; Pancreatic Cancer; Colorectal Cancer; Ovarian Cancer; Endometrial Cancer; Metastatic Cancer; Bladder Cancer; Cellular Therapy; NK Cell Therapy; Non-small-cell Lung Carcinoma
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplastic Processes; Neoplasms; Stomach Neoplasms; Neoplasm Metastasis; 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: ACE1702-001

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