Johanna C. Bendell, MD from Sarah Cannon discusses and ASCO 2020 abstract entitled A phase I/II, two-part, multicenter, first-in-human study of DS-7300a in patients with advanced solid malignant tumors
B7 homologue 3 (B7-H3) is a protein that is overexpressed in different forms of cancer, including squamous cell carcinoma of the lung, head and neck, prostate, esophageal, and breast. Overexpression of B7-H3 is related to poor prognosis because it facilitates increased cancer cell invasive and metastatic potential (Dong P, et al. Front Oncol. 2018;8:264). No targeted cancer therapies with B7-H3 are currently approved. DS-7300a is an antibody-drug conjugate made up of a monoclonal anti-B7-H3 IgG1 humanized antibody (MABX-9001a) conjugated to a drug linker that releases its payload upon cancer cell internalization. The payload, DXd, is a derivative of exatecan that inhibits topoisomerase I, an enzyme for replication and transcription that relaxes supercoiled DNA. DS-7300a induced in vitro apoptosis in cancer cells and demonstrated powerful antitumor activity in xenograft models of different forms of in vivo solid tumors.
In patients with selected advanced solid tumors (NCT04145622) this phase 1/2, multicenter, non-randomised, open-label, first-in-human study of DS-7300a is underway in the United States and Japan. There are 2 parts to this study: dose escalation (part 1) and dose expansion (part 2). The primary objectives are to assess DS-7300a 's protection, tolerability and antitumor activity and to evaluate the maximum tolerated dose or recommended dose for the expansion portion. Secondary goals include the pharmacokinetic characterization of DS-7300a, the determination of total antibody and drug portion anti-B7-H3 levels (DXd), and the occurrence of anti-drug antibodies against DS-7300a assessment. Main inclusion requirements are age between 18 years of age (US) or 20 years of age (Japan), ECOG output status of 0 or 1, RECIST 1.1 observable lesion as measured by the investigator, and agree to the provision of pre- and on-treatment tissue samples (obligatory if clinically approved and not contraindicated). Prior treatment with orlotamab, enoblituzumab, other B7-H3-targeted agents, or an antibody-drug conjugate that is conjugated with an inhibitor of topoisomerase I are main exclusion criteria. Three cohorts, including patients with selected advanced solid tumors, will initiate the dose expansion. DS-7300a will be intravenously administered in both parts on day 1 of each 21-day cycle. The starting dose of DS-7300a is 0.8 mg / kg during dose escalation. Currently, this trial is in the dose-escalation portion. Data on clinical trials: NCT04145622.