search
Back to results

A Study to Evaluate the Safety and Efficacy of A2B530, a Logic-gated CAR T, in Subjects With Solid Tumors That Express CEA and Have Lost HLA-A*02 Expression (EVEREST-1)

Primary Purpose

Solid Tumor, Adult, Solid Tumor, Pancreatic Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
A2B530
xT-Onco with HLA-LOH Assay
Sponsored by
A2 Biotherapeutics Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Solid Tumor, Adult focused on measuring CAR T Cell, Solid Tumors, autologous, T cell, Carcinoembryonic Antigen, CEA, HLA-A2, Solid Tumors Expressing CEA, Pancreatic Cancer, PANC, CRC, Colorectal Cancer, NSCLC, Non-Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria: Appropriately enrolled in the BASECAMP-1 A2 Biotherapeutics, Inc. study, with tissue demonstrating LOH of HLA-A*02:01 by NGS (whenever possible from the primary site), successful apheresis and PBMC processing, and with sufficient stored cells available for Tmod CAR T-cell therapy Histologically confirmed recurrent unresectable, locally advanced, or metastatic CRC, NSCLC, PANC, or other solid tumors associated with CEA expression. Measurable disease is required with lesions of >1.0 cm by computed tomography (CT). (Soluble CEA is not acceptable as the sole measure of disease). Received previous required therapy for the appropriate solid tumor disease as described in the protocol Has adequate organ function as described in the protocol ECOG performance status of 0 to 1 Life expectancy of ≥3 months Willing to comply with study schedule of assessments including long term safety follow up Key Exclusion Criteria: Has disease that is suitable for local therapy or able to receive standard of care therapy that is therapeutic and not palliative Prior allogeneic stem cell transplant Prior solid organ transplant Cancer therapy within 3 weeks or 3 half lives of A2B530 infusion Radiotherapy within 28 days of A2B530 infusion Unstable angina, arrhythmia, myocardial infarction, or any other significant cardiac disease within the last 6 months Any new symptomatic pulmonary embolism (PE) or a deep vein thrombosis (DVT) within 3 months of enrollment. Therapeutic dosing of anticoagulants is allowed for history of PE or DVT if greater than 3 months from time of enrollment, and adequately treated. Requires supplemental home oxygen Females of childbearing potential who are pregnant or breastfeeding Subjects, both male and female, of childbearing potential who are not willing to practice birth control from the time of consent through 6 months post infusion of A2B530

Sites / Locations

  • City of HopeRecruiting
  • UCLA Medical CenterRecruiting
  • Mayo Clinic Jacksonville
  • Moffitt Cancer CenterRecruiting
  • Mayo Clinic RochesterRecruiting
  • Washington UniversityRecruiting
  • NYU Langone Medical CenterRecruiting
  • MD Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

A2530

Arm Description

Patients receive Preconditioning Lymphodepletion (PCLD) Regimen followed by a single dose of A2B530 intravenously on day 0

Outcomes

Primary Outcome Measures

Phase 1: Rate of adverse events and dose limiting toxicities (DLTs) by dose level
Adverse Events and toxicity will be evaluated according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events version 5.0 (or current version). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events will be graded according to the criteria described in the current protocol.
Phase 1: Recommended Phase 2 Dose (RP2D)
The RP2D will be identified utilizing a BOIN study design in addition to considering safety and biomarker analysis.
Phase 2: The Overall Response Rate (ORR) for patients
The ORR will be evaluated per RECIST v1.1 and assessed by independent central review.

Secondary Outcome Measures

Persistence of A2B530
Number of A2B530 Tmod CAR T cells present in patients treated with A2B530 as assessed by Polymerase Chain Reaction (PCR) (or similar method) on participant blood samples
Cytokine analysis
Cytokine levels in patients treated with A2B530 assessed by cytokine analysis on participant blood samples

Full Information

First Posted
January 30, 2023
Last Updated
October 23, 2023
Sponsor
A2 Biotherapeutics Inc.
Collaborators
Tempus Labs
search

1. Study Identification

Unique Protocol Identification Number
NCT05736731
Brief Title
A Study to Evaluate the Safety and Efficacy of A2B530, a Logic-gated CAR T, in Subjects With Solid Tumors That Express CEA and Have Lost HLA-A*02 Expression
Acronym
EVEREST-1
Official Title
A Phase 1/2 Study to Evaluate the Safety and Efficacy of A2B530, an Autologous Logic-gated Tmod™ Chimeric Antigen Receptor T Cell (CAR T), in Heterozygous HLA-A*02 Adult Subjects With Recurrent Unresectable, Locally Advanced, or Metastatic Solid Tumors That Express CEA and Have Lost HLA-A*02 Expression
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 28, 2023 (Actual)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
December 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
A2 Biotherapeutics Inc.
Collaborators
Tempus Labs

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The goal of this study is to test A2B530,an autologous logic-gated Tmod™ CAR T-cell product in subjects with solid tumors including colorectal cancer (CRC), pancreatic cancer (PANC), non-small cell lung cancer (NSCLC), and other solid tumors that express CEA and have lost HLA-A*02 expression. The main questions this study aims to answer are: Phase 1: What is the maximum or recommended dose of A2B530 that is safe for patients Phase 2: Does the recommended dose of A2B530 kill the solid tumor cells and protect the patient's healthy cells Participants will be required to perform study procedures and assessments, and will also receive the following study treatments: Enrollment and Apheresis in BASECAMP-1 (NCT04981119) Preconditioning Lymphodepletion (PCLD) Regimen A2B530 Tmod CAR T cells at the assigned dose
Detailed Description
This is a phase 1/2, multi-center, open-label study that enrolls adult subjects with recurrent unresectable, locally advanced, or metastatic (considered non-curative) CRC, NSCLC, PANC, or other solid tumors with CEA expression. Subjects must be germline HLA-A*02 heterozygous, with tumors that express CEA and somatic loss of HLA-A*02. The purpose of Phase 1 of this study is to determine the safety and the optimal dose of A2B530 (after PCLD) in participants with solid tumor disease. The purpose of Phase 2 of this study is to determine the further safety and efficacy (how well it treats the solid tumor disease) of A2B530. The treatment available for these cancers and other solid tumors can be toxic, debilitating, and fatal. In the recurrent unresectable, locally advanced, or metastatic setting, the intent of standard of care treatment is typically palliative rather than curative, and has not changed significantly in several decades. A2 Bio hypothesizes that A2B530 Tmod CAR T-cell therapy will enable the killing of tumor target cells (those cells that express CEA and have LOH for HLA-A*02 protein). Additionally, normal healthy cells that maintain HLA-A*02 expression and co-express CEA (eg, gut mucosal tissue) will not be targeted due to the blocker portion of the Tmod CAR T cell that acts as a self-regulated safety switch that protects normal tissue from damage. A2 Bio believes this will provide a therapeutic safety window compared to previous solid tumor targeting therapies. This hypothesis will be explored in the study. Participants for this study must enroll and have their T cells collected (apheresis) in the pre-screening BASECAMP-1 study (NCT04981119). T cells are collected, processed and stored for each participant. Upon disease progression the participant may screen for this study (EVEREST-1) and the participant's T cells are then manufactured and infused following PCLD regimen. There is no time requirement between the studies, and patients may go directly from BASECAMP-1 to EVEREST-1 based on their own disease course.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumor, Adult, Solid Tumor, Pancreatic Cancer, Pancreatic Neoplasms, Pancreas Cancer, Non Small Cell Lung Cancer, Non Small Cell Lung Cancer Recurrent, Non-Small Cell Squamous Lung Cancer, NSCLC, NSCLC, Recurrent, Colorectal Cancer, Colorectal Neoplasms, Colorectal Adenocarcinoma, CRC, Colorectal Cancer Metastatic, Cancer
Keywords
CAR T Cell, Solid Tumors, autologous, T cell, Carcinoembryonic Antigen, CEA, HLA-A2, Solid Tumors Expressing CEA, Pancreatic Cancer, PANC, CRC, Colorectal Cancer, NSCLC, Non-Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A2530
Arm Type
Experimental
Arm Description
Patients receive Preconditioning Lymphodepletion (PCLD) Regimen followed by a single dose of A2B530 intravenously on day 0
Intervention Type
Biological
Intervention Name(s)
A2B530
Other Intervention Name(s)
Tmod CAR T-cell Therapy
Intervention Description
Autologous logic-gated Tmod CAR T-cells
Intervention Type
Diagnostic Test
Intervention Name(s)
xT-Onco with HLA-LOH Assay
Intervention Description
An investigational next generation sequencing (NGS) in vitro diagnostic (IVD) medical device
Primary Outcome Measure Information:
Title
Phase 1: Rate of adverse events and dose limiting toxicities (DLTs) by dose level
Description
Adverse Events and toxicity will be evaluated according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events version 5.0 (or current version). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events will be graded according to the criteria described in the current protocol.
Time Frame
From the time of Informed consent until 24 months (2 years) post A2B530 infusion.
Title
Phase 1: Recommended Phase 2 Dose (RP2D)
Description
The RP2D will be identified utilizing a BOIN study design in addition to considering safety and biomarker analysis.
Time Frame
21 days post A2B530 infusion
Title
Phase 2: The Overall Response Rate (ORR) for patients
Description
The ORR will be evaluated per RECIST v1.1 and assessed by independent central review.
Time Frame
24 months post A2B530 infusion
Secondary Outcome Measure Information:
Title
Persistence of A2B530
Description
Number of A2B530 Tmod CAR T cells present in patients treated with A2B530 as assessed by Polymerase Chain Reaction (PCR) (or similar method) on participant blood samples
Time Frame
up to 24 months post A2B530 infusion
Title
Cytokine analysis
Description
Cytokine levels in patients treated with A2B530 assessed by cytokine analysis on participant blood samples
Time Frame
up to 24 months post A2B530 infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Appropriately enrolled in the BASECAMP-1 A2 Biotherapeutics, Inc. study, with tissue demonstrating LOH of HLA-A*02:01 by NGS (whenever possible from the primary site), successful apheresis and PBMC processing, and with sufficient stored cells available for Tmod CAR T-cell therapy Histologically confirmed recurrent unresectable, locally advanced, or metastatic CRC, NSCLC, PANC, or other solid tumors associated with CEA expression. Measurable disease is required with lesions of >1.0 cm by computed tomography (CT). (Soluble CEA is not acceptable as the sole measure of disease). Received previous required therapy for the appropriate solid tumor disease as described in the protocol Has adequate organ function as described in the protocol ECOG performance status of 0 to 1 Life expectancy of ≥3 months Willing to comply with study schedule of assessments including long term safety follow up Key Exclusion Criteria: Has disease that is suitable for local therapy or able to receive standard of care therapy that is therapeutic and not palliative Prior allogeneic stem cell transplant Prior solid organ transplant Cancer therapy within 3 weeks or 3 half lives of A2B530 infusion Radiotherapy within 28 days of A2B530 infusion Unstable angina, arrhythmia, myocardial infarction, or any other significant cardiac disease within the last 6 months Any new symptomatic pulmonary embolism (PE) or a deep vein thrombosis (DVT) within 3 months of enrollment. Therapeutic dosing of anticoagulants is allowed for history of PE or DVT if greater than 3 months from time of enrollment, and adequately treated. Requires supplemental home oxygen Females of childbearing potential who are pregnant or breastfeeding Subjects, both male and female, of childbearing potential who are not willing to practice birth control from the time of consent through 6 months post infusion of A2B530
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Trials
Phone
310-431-9180
Email
ClinicalTrials@a2bio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Ng, MD
Organizational Affiliation
Sr. Medical Director, Safety, A2 Biotherapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
90101
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Janela Agonoy
Email
jagonoy@coh.org
First Name & Middle Initial & Last Name & Degree
Marwan Fakih, MD
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90404
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christopher Hannigan
Email
channigan@mednet.ucla.edu
First Name & Middle Initial & Last Name & Degree
J. Randolph Hecht, MD
Facility Name
Mayo Clinic Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Herman Murthy, MD
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephanie Galvez-hernandez
Email
stephanie.galvez-hernandez@moffitt.org
First Name & Middle Initial & Last Name & Degree
Kedar Kirtane, MD
Facility Name
Mayo Clinic Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yidan Wang
Email
wang.yidan@mayo.edu
First Name & Middle Initial & Last Name & Degree
Julian Molina, MD, PhD
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amberly Scott
Email
amberly@wustl.edu
First Name & Middle Initial & Last Name & Degree
Patrick Grierson, MD PhD
Facility Name
NYU Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Salman Punekar, MD
Phone
212-731-6228
Email
Salman.Punekar@nyulangone.org
First Name & Middle Initial & Last Name & Degree
Maria Herrmann
Email
maria.herrmann@nyulangone.org
First Name & Middle Initial & Last Name & Degree
Salman Punekar, MD
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kaitlin Gandy
Email
ksgandy@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Maria Pia Morelli, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Study data will be shared within 1 year of study completion.
IPD Sharing Time Frame
Data will be available within 1 year of the completion of the study, the length of time of availability is to be determined.
Citations:
PubMed Identifier
33012527
Citation
Hamburger AE, DiAndreth B, Cui J, Daris ME, Munguia ML, Deshmukh K, Mock JY, Asuelime GE, Lim ED, Kreke MR, Tokatlian T, Kamb A. Engineered T cells directed at tumors with defined allelic loss. Mol Immunol. 2020 Dec;128:298-310. doi: 10.1016/j.molimm.2020.09.012. Epub 2020 Oct 1.
Results Reference
background
PubMed Identifier
33731480
Citation
Hwang MS, Mog BJ, Douglass J, Pearlman AH, Hsiue EH, Paul S, DiNapoli SR, Konig MF, Pardoll DM, Gabelli SB, Bettegowda C, Papadopoulos N, Vogelstein B, Zhou S, Kinzler KW. Targeting loss of heterozygosity for cancer-specific immunotherapy. Proc Natl Acad Sci U S A. 2021 Mar 23;118(12):e2022410118. doi: 10.1073/pnas.2022410118.
Results Reference
background
Citation
Perera J, Mapes B, Lau D, et al. Detection of human leukocyte antigen class I loss of heterozygosity in solid tumor types by next-generation DNA sequencing. J Immunother Cancer. 2019, 7(Suppl 1):P103
Results Reference
background
PubMed Identifier
20164920
Citation
Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, Mc Henry KT, Pinchback RM, Ligon AH, Cho YJ, Haery L, Greulich H, Reich M, Winckler W, Lawrence MS, Weir BA, Tanaka KE, Chiang DY, Bass AJ, Loo A, Hoffman C, Prensner J, Liefeld T, Gao Q, Yecies D, Signoretti S, Maher E, Kaye FJ, Sasaki H, Tepper JE, Fletcher JA, Tabernero J, Baselga J, Tsao MS, Demichelis F, Rubin MA, Janne PA, Daly MJ, Nucera C, Levine RL, Ebert BL, Gabriel S, Rustgi AK, Antonescu CR, Ladanyi M, Letai A, Garraway LA, Loda M, Beer DG, True LD, Okamoto A, Pomeroy SL, Singer S, Golub TR, Lander ES, Getz G, Sellers WR, Meyerson M. The landscape of somatic copy-number alteration across human cancers. Nature. 2010 Feb 18;463(7283):899-905. doi: 10.1038/nature08822.
Results Reference
background
PubMed Identifier
35235342
Citation
Sandberg ML, Wang X, Martin AD, Nampe DP, Gabrelow GB, Li CZ, McElvain ME, Lee WH, Shafaattalab S, Martire S, Fisher FA, Ando Y, Liu E, Ju D, Wong LM, Xu H, Kamb A. A carcinoembryonic antigen-specific cell therapy selectively targets tumor cells with HLA loss of heterozygosity in vitro and in vivo. Sci Transl Med. 2022 Mar 2;14(634):eabm0306. doi: 10.1126/scitranslmed.abm0306. Epub 2022 Mar 2.
Results Reference
background
Links:
URL
http://www.a2bio.com
Description
A2 Biotherapeutics Inc.
URL
https://clinicaltrials.gov/ct2/show/NCT04981119?term=LOH+Apheresis&cond=Cancer&cntry=US&draw=2&rank=1
Description
BASECAMP-1 Study

Learn more about this trial

A Study to Evaluate the Safety and Efficacy of A2B530, a Logic-gated CAR T, in Subjects With Solid Tumors That Express CEA and Have Lost HLA-A*02 Expression

We'll reach out to this number within 24 hrs