American Association for Cancer Research (AACR)

Clinical Cancer Research

, том 29 , издание 16 , страницы OF1-OF16

Preclinical Characterization and Phase 1 Trial Results of INBRX-109, a Third-Generation, Recombinant, Humanized, Death Receptor 5 Agonist Antibody, in Chondrosarcoma

Vivek Subbiah ¹

Sant P Chawla ²

Anthony Conley ³

Breelyn A. Wilky ⁴

Anthony W. Tolcher ⁵

Nehal J. Lakhani ⁶

David Berz ⁷

Vasily Andrianov ⁸

William Crago ⁸

Monica Holcomb ⁸

Abrahim Hussain ⁸

Carson Veldstra ⁸

James Kalabus ⁸

Brianne O’Neill ⁸

Lane Senne ⁸

Emily Rowell ⁸

Analeah B. Heidt ⁸

Katelyn M. Willis ⁸

Brendan P. Eckelman ⁸

Скрыть аффилиации авторов Показать аффилиации авторов: 8 аффилиаций

1Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas; Sarah Cannon Research Institute, Nashville, Tennessee. |

2Sarcoma Oncology Research Center, Santa Monica, California. |

3Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. |

⁴

4Department of Medicine, Division of Medical Oncology, University of Colorado School of Medicine, Aurora, Colorado. |

⁵

5NEXT Oncology, San Antonio, Texas. |

⁶

6START Midwest, Michigan. |

⁷

7Valkyrie Clinical Trials, Los Angeles, California. |

⁸

8Inhibrx, Inc, La Jolla, California. |

Тип публикации: Journal Article

Дата публикации: 2023-06-02

American Association for Cancer Research (AACR)

Clinical Cancer Research

scimago Q1

wos Q1

БС1

SJR: 4.800

CiteScore: 19.0

Impact factor: 10.2

ISSN: 10780432, 15573265

DOI: 10.1158/1078-0432.ccr-23-0974

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PubMed ID: 37265425

Cancer Research

Oncology

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Purpose:

Patients with unresectable/metastatic chondrosarcoma have poor prognoses; conventional chondrosarcoma is associated with a median progression-free survival (PFS) of <4 months after first-line chemotherapy. No standard targeted therapies are available. We present the preclinical characterization of INBRX-109, a third-generation death receptor 5 (DR5) agonist, and clinical findings from a phase I trial of INBRX-109 in unresectable/metastatic chondrosarcoma (NCT03715933).

Patients and Methods:

INBRX-109 was first characterized preclinically as a DR5 agonist, with binding specificity and hepatotoxicity evaluated in vitro and antitumor activity evaluated both in vitro and in vivo. INBRX-109 (3 mg/kg every 3 weeks) was then evaluated in a phase I study of solid tumors, which included a cohort with any subtype of chondrosarcoma and a cohort with IDH1/IDH2-mutant conventional chondrosarcoma. The primary endpoint was safety. Efficacy was an exploratory endpoint, with measures including objective response, disease control rate, and PFS.

Results:

In preclinical studies, INBRX-109 led to antitumor activity in vitro and in patient-derived xenograft models, with minimal hepatotoxicity. In the phase I study, INBRX-109 was well tolerated and demonstrated antitumor activity in unresectable/metastatic chondrosarcoma. INBRX-109 led to a disease control rate of 87.1% [27/31; durable clinical benefit, 40.7% (11/27)], including two partial responses, and median PFS of 7.6 months. Most treatment-related adverse events, including liver-related events, were low grade (grade ≥3 events in chondrosarcoma cohorts, 5.7%).

Conclusions:

INBRX-109 demonstrated encouraging antitumor activity with a favorable safety profile in patients with unresectable/metastatic chondrosarcoma. A randomized, placebo-controlled, phase II trial (ChonDRAgon, NCT04950075) will further evaluate INBRX-109 in conventional chondrosarcoma.

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Subbiah V. et al. Preclinical Characterization and Phase 1 Trial Results of INBRX-109, a Third-Generation, Recombinant, Humanized, Death Receptor 5 Agonist Antibody, in Chondrosarcoma // Clinical Cancer Research. 2023. Vol. 29. No. 16. p. OF1-OF16.

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Subbiah V., Chawla S. P., Conley A., Wilky B. A., Tolcher A. W., Lakhani N. J., Berz D., Andrianov V., Crago W., Holcomb M., Hussain A., Veldstra C., Kalabus J., O’Neill B., Senne L., Rowell E., Heidt A. B., Willis K. M., Eckelman B. P. Preclinical Characterization and Phase 1 Trial Results of INBRX-109, a Third-Generation, Recombinant, Humanized, Death Receptor 5 Agonist Antibody, in Chondrosarcoma // Clinical Cancer Research. 2023. Vol. 29. No. 16. p. OF1-OF16.

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TY - JOUR

DO - 10.1158/1078-0432.ccr-23-0974

UR - https://doi.org/10.1158/1078-0432.ccr-23-0974

TI - Preclinical Characterization and Phase 1 Trial Results of INBRX-109, a Third-Generation, Recombinant, Humanized, Death Receptor 5 Agonist Antibody, in Chondrosarcoma

T2 - Clinical Cancer Research

AU - Subbiah, Vivek

AU - Chawla, Sant P

AU - Conley, Anthony

AU - Wilky, Breelyn A.

AU - Tolcher, Anthony W.

AU - Lakhani, Nehal J.

AU - Berz, David

AU - Andrianov, Vasily

AU - Crago, William

AU - Holcomb, Monica

AU - Hussain, Abrahim

AU - Veldstra, Carson

AU - Kalabus, James

AU - O’Neill, Brianne

AU - Senne, Lane

AU - Rowell, Emily

AU - Heidt, Analeah B.

AU - Willis, Katelyn M.

AU - Eckelman, Brendan P.

PY - 2023

DA - 2023/06/02

PB - American Association for Cancer Research (AACR)

SP - OF1-OF16

IS - 16

VL - 29

PMID - 37265425

SN - 1078-0432

SN - 1557-3265

ER -

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@article{2023_Subbiah,

author = {Vivek Subbiah and Sant P Chawla and Anthony Conley and Breelyn A. Wilky and Anthony W. Tolcher and Nehal J. Lakhani and David Berz and Vasily Andrianov and William Crago and Monica Holcomb and Abrahim Hussain and Carson Veldstra and James Kalabus and Brianne O’Neill and Lane Senne and Emily Rowell and Analeah B. Heidt and Katelyn M. Willis and Brendan P. Eckelman},

title = {Preclinical Characterization and Phase 1 Trial Results of INBRX-109, a Third-Generation, Recombinant, Humanized, Death Receptor 5 Agonist Antibody, in Chondrosarcoma},

journal = {Clinical Cancer Research},

year = {2023},

volume = {29},

publisher = {American Association for Cancer Research (AACR)},

month = {jun},

url = {https://doi.org/10.1158/1078-0432.ccr-23-0974},

number = {16},

pages = {OF1--OF16},

doi = {10.1158/1078-0432.ccr-23-0974}

}

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Subbiah, Vivek, et al. “Preclinical Characterization and Phase 1 Trial Results of INBRX-109, a Third-Generation, Recombinant, Humanized, Death Receptor 5 Agonist Antibody, in Chondrosarcoma.” Clinical Cancer Research, vol. 29, no. 16, Jun. 2023, pp. OF1-OF16. https://doi.org/10.1158/1078-0432.ccr-23-0974.