Relationship of pharmacokinetics (PK), toxicity, and initial evidence of clinical activity with IMGN853, a folate receptor alpha (FRa) targeting antibody drug conjugate in patients (Pts) with epithelial ovarian cancer (EOC) and other FRa-positive solid tumors.

5571 Background: IMGN853 is a FRα-targeting ADC that comprises a FRa-binding antibody conjugated with the potent maytansinoid tubulin inhibitor, DM4. FRa is highly expressed on many solid tumors, particularly EOC, endometrial, non-small cell lung cancer, and clear cell renal cancer Methods: The phase I primary objectives are to determine the maximum tolerated dose and recommended phase 2 dose. The secondary objectives include evaluation of safety, PK, pharmacodynamics and preliminary efficacy. Analysis of PK data and the relationship with ocular toxicity, the dose limiting toxicity at 7.0 mg/kg total body weight (TBW) and initial evidence of clinical activity from patients in this ongoing study is described. Results: Thirty pts have been enrolled across 7 dose levels 0.15 to 7.0 mg/kg TBW (IV) every 21 days (Q3W). The occurrence of ocular toxicity was associated with high Cmax (p=0.0004 Fisher exact test) and high early exposure levels, (area under the curve in the first 24 hours (AUC0-24) (p=0.0001)). Co...