Preliminary dose escalation results from a phase I/II, first-in-human study of MGC018 (anti-B7-H3 antibody-drug conjugate) in patients with advanced solid tumors

3071 Background: Antibody-drug conjugates (ADCs) are cancer agents that have a cytotoxic payload linked to a monoclonal antibody (mAb) that target cancer cells. ADCs offer increased cytotoxic activity while reducing normal tissue exposure. B7-H3 is expressed on multiple solid tumors with limited normal tissue expression. MGC018 is an investigational ADC with a duocarmycin payload linked to an anti-B7-H3 mAb. It is hypothesized that MGC018 has activity against B7-H3 expressing tumors with an acceptable safety profile. Methods: This study evaluates safety, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD) of MGC018 in a dose escalation 3+3+3 design. In addition, pharmacokinetics, immunogenicity, and tumor response using RECIST v1.1 are evaluated. Cohort expansion will enroll at the MTD to assess safety and tumor response. Results: The study is enrolling Cohort 3 (6 total cohorts planned) in dose escalation. 20 patients (pts) were enrolled as of Feb 03, 2020. At least 1 treatment related adverse event (TRAE) occurred in 16 pts (80.0%). The most common TRAEs were neutropenia/decreased neutrophil count (35%); fatigue, lymphopenia/decreased lymphocyte count (30.0%); palmar plantar erythrodysaesthesia (PPE), skin hyperpigmentation (25.0%); pruritis, nausea, chills, infusion related reaction (20.0%); and vomiting, pyrexia, maculopapular rash (15.0%). Eleven pts (55.0%) experienced TRAEs ≥ Grade 3; events were decreased lymphocyte count/lymphopenia (n = 6), decreased neutrophil count/neutropenia (n = 3), PPE (n = 2), and maculopapular rash (n = 2). Three related serious adverse events occurred in 3 unique pts: pneumonitis in a pt with concurrent bacterial pneumonia, non-infectious gastroenteritis, and stasis dermatitis in a pt with chronic venous insufficiency. One DLT has occurred (Grade 4 neutropenia). No febrile neutropenia was observed. Target lesion decrease was noted in 1 pt each with small cell lung cancer (-6.3%), non-small cell lung cancer (-23.8%), and metastatic castrate-resistant prostate cancer (mCRPC) (-29.4%) with PSA change from 82.8 ng/ml to 57.1 ng/ml. One mCRPC pt with bone only disease had substantial improvement on bone scan and PSA decrease from 60 ng/ml to 4.7 ng/ml. Conclusions: Results to date demonstrate a manageable safety profile with early evidence of clinical activity. Continued dose escalation and clinical investigation of MGC018 is ongoing. Clinical trial information: NCT03729596 .