ACE2016 in Adult Subjects With Locally Advanced or Metastatic Solid Tumors Expressing Epidermal Growth Factor Receptor (EGFR)

A Phase 1 Multicenter Study Evaluating the Safety and Efficacy of ACE2016, an Allogeneic Anti-EGFR Conjugated Gamma Delta T Cell (gdT) Therapy in Adult Subjects With Locally Advanced or Metastatic Solid Tumors Expressing Epidermal Growth Factor Receptor (EGFR)

ACE2016 is an off-the-shelf, allogeneic gamma delta T (gdT) cell therapy derived from healthy donors, that is under investigation for the treatment of Locally Advanced or Metastatic Solid Tumors Expressing Epidermal Growth Factor Receptor (EGFR).

The ACE2016-001 study is an open-label, Phase I, first-in-human (FIH) study that aims to evaluate the safety and tolerability, persistency, pharmacodynamics and efficacy of ACE2016 in patients with Locally Advanced or Metastatic Solid Tumors Expressing Epidermal Growth Factor Receptor (EGFR).

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Solid Tumor; Locally Advanced Solid Tumor
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: ACE2016; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Stephanie Chien; Phone Number: +1 415 366 7822; Email: clinical@acepodiabio.com

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • SCRI Denver Drug Development Unit
      • Principal Investigator: Jason Henry, MD
      • Contact: James Vick
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute (SCRI) Oncology Partners
      • Principal Investigator: Meredith Pelster, MD
      • Contact: Emily Lay Petcu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Locally advanced unresectable or metastatic solid tumors that have failed at least two lines of therapy (one of which must be targeted therapy)
• At least one measurable lesion as defined by RECIST v1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Adequate hematologic and renal, hepatic and cardiac function
• Oxygen saturation via pulse oximeter ≥92% at rest on room air

Exclusion Criteria:

• Prior treatment with a genetically modified cell therapy product targeting EGFR
• History of allogeneic transplantation
• Subjects with active CNS metastases
• History or presence of clinically relevant Central Nervous System (CNS) disorder (e.g. epilepsy)
• Clinically significant active infection
• Human Immunodeficiency Virus (HIV) infection, active hepatitis B infection, or hepatitis C infection.
• History of malignancies with the exception of certain treated malignancies with no evidence of disease.
• Primary immunodeficiency disorder
• Pregnant or lactating female
• Any medical, psychological, familial, or sociological conditions that, in the opinion of the Investigator or Sponsor Medical Monitor, would impair the ability of the subject to receive study treatment or comply with study requirements, including understanding and rendering of informed consent

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACE2016 ONLY: 1 DOSE; ACE2016 dose escalation, monotherapy. Lymphodepleting regimen followed by escalating doses of ACE2016.	Drug: Cyclophosphamide; Lymphodepleting agent; Drug: Fludarabine; Lymphodepleting agent; Drug: ACE2016; Allogeneic gamma delta T (gdT) cell therapy
Experimental: ACE2016 ONLY: 3 DOSES; ACE2016 recommended dose, monotherapy. Lymphodepleting regimen followed by recommended dose of ACE2016.	Drug: Cyclophosphamide; Lymphodepleting agent; Drug: Fludarabine; Lymphodepleting agent; Drug: ACE2016; Allogeneic gamma delta T (gdT) cell therapy
Experimental: ACE2016 AND PEMBROLIZUMAB: 3 DOSES; ACE2016 recommended dose, in combination with pembrolizumab. Lymphodepleting regimen followed by recommended dose of ACE2016, giving in combination with pembrolizumab.	Drug: Cyclophosphamide; Lymphodepleting agent; Drug: Fludarabine; Lymphodepleting agent; Drug: ACE2016; Allogeneic gamma delta T (gdT) cell therapy; Drug: Pembrolizumab; Immune checkpoint anti-PD-1 antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of DLTs, AESIs, Grade 3 or higher TEAEs, TEAEs considered related to ACE2016, TEAEs resulting in death, SAEs, related SAEs, and TEAEs leading to treatment discontinuation will be summarized by cohort		1 year
Change from baseline in clinical laboratory tests results	Number of subject with change from baseline clinical significant lab findings by cohort (descriptive)	1 year
Change from baseline in vital signs results	Number of subjects with change from baseline clinical significant vital signs findings by cohort (descriptive)	1 year
Recommended Dose (RD)		1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistence of ACE2016 before and after administration	Half-life of ACE2016	1 year
Measure of anti-ACE2016 antibodies after administration	Titration of anti-ACE2016 antibodies after administration	1 year
Objective Response Rate (ORR)	Proportion of subjects assessed as having a complete response (CR) or partial response (PR) according to RECIST v1.1	1 year
Disease Control Rate (DCR)	Number of subjects with a complete response (CR), partial response (PR) or stable disease (SD) as defined by RECIST v1.1	1 year
Duration Of Response (DOR)	Duration (time) from the first tumor assessment showing response per RECIST v1.1 to the time of disease progression or death.	1 year
Progression Free Survival (PFS)	Duration (time) from first ACE2016 cell infusion to first documentation of disease progression per RECIST v1.1 or death	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics of ACE2016	Change from baseline IL2,6,8,10 IFN TNF, and change in TBNK cell subsets.	1 year
gdT infiltration in tumor mass	Optional biopsy to examine gdT cell infiltration	1 year

Collaborators and Investigators

• Sponsor: Acepodia Biotech, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): May 31, 2024
• Primary Completion (Estimated): December 18, 2026
• Study Completion (Estimated): March 25, 2027

Study Registration Dates

• First Submitted: April 30, 2024
• First Submitted That Met QC Criteria: May 10, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 10, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Cyclophosphamide; Pembrolizumab; Fludarabine
• Other Study ID Numbers: ACE2016-001

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