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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; Gastric Cancer; Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: AB-201

• Study Type: Interventional
• Enrollment (Anticipated): 133
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: AB-201-01 Study Team; Phone Number: 858-267-4465; Email: AB-201-01StudyTeam@ArtivaBio.com

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Suwon, Gyeonggi-do, Korea, Republic of, 16247
      • The Catholic university of Korea, St. Vincent's Hospital
      • Contact: Byoung Y Shim, MD
      • Principal Investigator: Byoung Y Shim, MD
• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Science University (OHSU)
      • Contact: Yazan Migdady, MD
      • Principal Investigator: Yazan Migdady, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (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 ≥ 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.

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 2 Cohort A; 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: Cyclophosphamide; Lymphodepleting chemotherapy; Drug: Fludarabine; Lymphodepleting chemotherapy; Drug: AB-201; NK Cell Therapy
Experimental: Phase 2 Cohort B; 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: Cyclophosphamide; Lymphodepleting chemotherapy; Drug: Fludarabine; Lymphodepleting chemotherapy; Drug: AB-201; NK Cell Therapy
Experimental: Phase 2 Cohort C; 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: Cyclophosphamide; Lymphodepleting chemotherapy; Drug: Fludarabine; Lymphodepleting chemotherapy; Drug: AB-201; NK Cell Therapy
Experimental: Phase 1 Dose Confirmation; Dose Confirmation of AB-201 in advanced metastatic breast cancer, gastric or gastroesophageal junction adenocarcinoma with HER2 overexpression	Drug: Cyclophosphamide; Lymphodepleting chemotherapy; Drug: Fludarabine; Lymphodepleting chemotherapy; Drug: AB-201; NK Cell Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: Artiva Biotherapeutics, Inc.
• Investigators: Study Director: Thorsten Graef, MD, Ph.D, Artiva Biotherapeutics

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2023
• Primary Completion (Anticipated): April 1, 2027
• Study Completion (Anticipated): April 1, 2027

Study Registration Dates

• First Submitted: December 23, 2022
• First Submitted That Met QC Criteria: December 23, 2022
• First Posted (Actual): January 10, 2023

Study Record Updates

• Last Update Posted (Estimate): May 4, 2023
• Last Update Submitted That Met QC Criteria: May 2, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

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

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