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

Preclinical Characterization and Phase I Trial Results
of INBRX-109, A Third-Generation, Recombinant,
Humanized, Death Receptor 5 Agonist Antibody,
in Chondrosarcoma
Vivek Subbiah1, Sant P. Chawla2, Anthony P. Conley3, Breelyn A. Wilky4, Anthony Tolcher5,
Nehal J. Lakhani6, David Berz7, Vasily Andrianov8, William Crago8, Monica Holcomb8, Abrahim Hussain8,
Carson Veldstra8, James Kalabus8, Brianne O’Neill8, Lane Senne8, Emily Rowell8, Analeah B. Heidt8,
Katelyn M. Willis8, and Brendan P. Eckelman8


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.

Subbiah et al_INBRX-109 Preclinical and Ph1 Data in Chondrosarcoma_CCR 2023.pdf