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    DRUG CLASS:

    CEA-targeted CAR-T immunotherapy

    Related drugs:
    2ms
    EVEREST-1: initial safety data from a seamless phase 1/2 study of A2B530, a logic-gated Tmod CAR T-cell therapy, in patients with solid tumors associated with CEA expression also exhibiting HLA-LOH (SITC 2024)
    β2M shRNA, beta–2–microglobulin short–hairpin RNA; CD, cluster of differentiation; EF1α, elongation factor–1 alpha; LIR, leukocyte immunoglobulin–like receptor; scFv, single–chain variable fragment; T2A, thosea asigna virus 2ADownload figure Open in new tab Download powerpoint Abstract 588 Figure 2 EVEREST-1 study design. BOIN, Bayesian optimal interval design; PCLD, preconditioning lymphodepletion; RP2D, recommended phase 2 dose
    Clinical • P1/2 data • CAR T-Cell Therapy
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    HLA-A (Major Histocompatibility Complex, Class I, A) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • CEACAM5 (CEA Cell Adhesion Molecule 5) • B2M (Beta-2-microglobulin) • GZMB (Granzyme B)
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    CEACAM5 expression • HLA-A*02
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    Tempus HLA-LOH assay
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    A2B530
    7ms
    EVEREST-1: A seamless phase 1/2 study of A2B530, a carcinoembryonic antigen (CEA) logic-gated Tmod CAR T-cell therapy, in patients with solid tumors associated with CEA expression also exhibiting human leukocyte antigen (HLA)-A*02 loss of heterozygosity (LOH). (ASCO 2024)
    Sci Transl Med. 2022.
    CAR T-Cell Therapy • P1/2 data • Clinical • IO biomarker
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    CEACAM5 (CEA Cell Adhesion Molecule 5)
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    A2B530
    9ms
    An Exploratory Clinical Study Evaluating the Safety and Efficacy of Anti-CEA-CAR-T Cells Injection in Patients With CEA+ Locally Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=9, Recruiting, China Medical University, China | Not yet recruiting --> Recruiting
    Enrollment open
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    CEACAM5 (CEA Cell Adhesion Molecule 5)
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    CEACAM5 expression • CEACAM5 overexpression
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    cyclophosphamide • fludarabine IV • anti-CEA-CAR-T
    11ms
    EVEREST-1: 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 (clinicaltrials.gov)
    P1/2, N=160, Recruiting, A2 Biotherapeutics Inc.
    Trial completion date • Trial primary completion date • CAR T-Cell Therapy • Metastases
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    HLA-A (Major Histocompatibility Complex, Class I, A) • CEACAM5 (CEA Cell Adhesion Molecule 5)
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    CEACAM5 expression • HLA-A*02
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    A2B530
    12ms
    Intraperitoneal administration of carcinoembryonic antigen-directed chimeric antigen receptor T cells is a robust delivery route for effective treatment of peritoneal carcinomatosis from colorectal cancer in pre-clinical study. (PubMed, Cytotherapy)
    Taken together, our data suggest that i.p. administration of CAR T cells may be a robust delivery route for effective treatment of cancer.
    Preclinical • Journal • CAR T-Cell Therapy
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    CEACAM5 (CEA Cell Adhesion Molecule 5) • PSCA (Prostate Stem Cell Antigen 2)
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    C-13-60
    1year
    EVEREST-1: A seamless phase 1/2 study of CEA logic-gated Tmod CAR T-cell therapy (A2B530) in patients with solid tumors associated with CEA expression also exhibiting HLA loss of heterozygosity (LOH) (SITC 2023)
    The primary objective of phase 1 is to evaluate the safety and tolerability of A2B530 in patients with NSCLC, CRC, and PANC, and to identify the maximum tolerated dose and recommended phase 2 dose (RP2D). The dose-expansion phase will confirm RP2D and collect biomarker data to further characterize A2B530.
    CAR T-Cell Therapy • P1/2 data • Clinical • IO biomarker
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    HLA-A (Major Histocompatibility Complex, Class I, A) • CEACAM5 (CEA Cell Adhesion Molecule 5)
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    CEACAM5 expression • HLA-A*02
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    Tempus HLA-LOH assay
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    A2B530
    1year
    BASECAMP-1: A master prescreening study to identify patients with high-risk or metastatic solid tumors with HLA loss of heterozygosity (LOH) in preparation for Tmod CAR T-cell therapy trials (SITC 2023)
    BASECAMP-1 is an ongoing prescreening study to: 1) Identify patients with tumor-associated HLA LOH and eligible for Tmod CAR T-cell therapy, and 2) Obtain leukapheresis in preparation for the autologous CAR T-cell therapy trials EVEREST-1 (A2B530 targeting carcinoembryonic antigen; NCT05736731) and EVEREST-2 (A2B694 targeting mesothelin). We have identified 52 patients across sites with study-specific disease types with HLA-A*02:01 LOH; of these, 13 are currently being screened, 23 have been found ineligible, and 16 have consented. This demonstrated the feasibility of leveraging a diagnostic during routine clinical workup to identify rare, molecularly defined patients for personalized clinical studies.
    CAR T-Cell Therapy • Clinical • Metastases
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    HLA-A (Major Histocompatibility Complex, Class I, A) • MSLN (Mesothelin) • CEACAM5 (CEA Cell Adhesion Molecule 5)
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    HLA-A*02
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    Tempus HLA-LOH assay
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    A2B530
    1year
    An Exploratory Clinical Study Evaluating the Safety and Efficacy of Anti-CEA-CAR-T Cells Injection in Patients With CEA+ Locally Advanced and/or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=9, Not yet recruiting, China Medical University, China
    New P1 trial • CAR T-Cell Therapy • Metastases
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    CEACAM5 (CEA Cell Adhesion Molecule 5)
    |
    CEACAM5 expression • CEACAM5 overexpression
    |
    cyclophosphamide • fludarabine IV • anti-CEA-CAR-T
    over1year
    EVEREST-1: 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 (clinicaltrials.gov)
    P1/2, N=160, Recruiting, A2 Biotherapeutics Inc. | Not yet recruiting --> Recruiting
    Enrollment open • CAR T-Cell Therapy • Metastases
    |
    HLA-A (Major Histocompatibility Complex, Class I, A) • CEACAM5 (CEA Cell Adhesion Molecule 5)
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    CEACAM5 expression • HLA-A*02
    |
    A2B530
    almost2years
    EVEREST-1: 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 (clinicaltrials.gov)
    P1/2, N=160, Not yet recruiting, A2 Biotherapeutics Inc.
    New P1/2 trial • CAR T-Cell Therapy • Metastases
    |
    HLA-A (Major Histocompatibility Complex, Class I, A) • CEACAM5 (CEA Cell Adhesion Molecule 5)
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    CEACAM5 expression • HLA-A*02
    |
    A2B530
    almost2years
    Tumor Growth Suppression of Pancreatic Cancer Orthotopic Xenograft Model by CEA-Targeting CAR-T Cells. (PubMed, Cancers (Basel))
    Thus, the therapeutic effect of CAR-T therapy was related to the target antigen expression level, and the further retrospective analysis of pathological findings from PDAC patients showed a correlation between the intensity of CEA immunostaining and tumor heterogeneity. Therefore, CEA expression levels in biopsies or surgical specimens can be clinically used as biomarkers to select PDAC patients for anti-CAR-T therapy.
    Preclinical • Journal • CAR T-Cell Therapy • IO biomarker
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    CEACAM5 (CEA Cell Adhesion Molecule 5)
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    CEACAM5 expression • CEACAM5 overexpression
    2years
    A2B530, an autologous CEA-directed Tmod T-cell therapy with an inhibitory receptor gated by HLA-A*02 to target colorectal, pancreatic, and lung cancer (SITC 2022)
    BASECAMP-1 ( NCT04981119 ), an observational study identifying patients with somatic HLA LOH, is recruiting. Eligible patients with metastatic colorectal, pancreatic, or non-small cell lung cancer will be apheresed for a future A2B530 EVEREST-1 interventional study.
    IO biomarker
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    HLA-A (Major Histocompatibility Complex, Class I, A) • CEACAM5 (CEA Cell Adhesion Molecule 5) • LILRB1 (Leukocyte Immunoglobulin Like Receptor B1)
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    CEACAM5 expression • HLA-A*02
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    A2B530
    over2years
    CAR-T Intraperitoneal Infusions for CEA-Expressing Adenocarcinoma Peritoneal Metastases or Malignant Ascites (IPC) (clinicaltrials.gov)
    P1, N=0, Withdrawn, Sorrento Therapeutics, Inc. | N=18 --> 0 | Active, not recruiting --> Withdrawn
    Enrollment change • Trial withdrawal • CAR T-Cell Therapy
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    CEACAM5 (CEA Cell Adhesion Molecule 5)
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    CEACAM5 expression
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    gene-modified anti-CEA T cells
    over2years
    Study of Anti-CEA CAR-T + Chemotherapy VS Chemotherapy Alone in Patients With CEA+Pancreatic Cancer & Liver Metastases (clinicaltrials.gov)
    P2b, N=0, Withdrawn, Sorrento Therapeutics, Inc. | N=167 --> 0 | Not yet recruiting --> Withdrawn
    Enrollment change • Trial withdrawal • CAR T-Cell Therapy
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    CEACAM5 (CEA Cell Adhesion Molecule 5)
    |
    CEACAM5 expression
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    gemcitabine • 5-fluorouracil • capecitabine • albumin-bound paclitaxel • leucovorin calcium • Onivyde (nanoliposomal irinotecan) • gene-modified anti-CEA T cells
    3years
    HITM-SURE: CAR-T Hepatic Artery Infusions or Pancreatic Venous Infusions for CEA-Expressing Liver Metastases or Pancreas Cancer (clinicaltrials.gov)
    P1, N=5, Completed, Roger Williams Medical Center | Active, not recruiting --> Completed | Trial completion date: Feb 2021 --> Sep 2021
    Trial completion • Trial completion date
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    CEACAM5 (CEA Cell Adhesion Molecule 5)
    |
    CEACAM5 expression
    |
    gene-modified anti-CEA T cells
    4years
    HITM-SURE: CAR-T Hepatic Artery Infusions or Pancreatic Venous Infusions for CEA-Expressing Liver Metastases or Pancreas Cancer (clinicaltrials.gov)
    P1, N=5, Active, not recruiting, Roger Williams Medical Center | Trial completion date: Aug 2020 --> Feb 2021
    Trial completion date
    |
    CEACAM5 (CEA Cell Adhesion Molecule 5)
    |
    CEACAM5 expression
    |
    gene-modified anti-CEA T cells
    4years
    CAR-T Intraperitoneal Infusions for CEA-Expressing Adenocarcinoma Peritoneal Metastases or Malignant Ascites (IPC) (clinicaltrials.gov)
    P1, N=18, Active, not recruiting, Sorrento Therapeutics, Inc. | Trial completion date: Sep 2020 --> Mar 2021 | Trial primary completion date: Sep 2020 --> Dec 2020
    Clinical • Trial completion date • Trial primary completion date • CAR T-Cell Therapy
    |
    CEACAM5 (CEA Cell Adhesion Molecule 5)
    |
    CEACAM5 expression
    |
    gene-modified anti-CEA T cells