A phase I dose-escalation study of IMGN388 in patients with solid tumors.

3058 Background: IMGN388 is a novel antibody-drug conjugate (ADC) composed of an integrin-targeting fully human antibody with the maytansinoid, DM4, attached via a covalent bond. IMGN388 has shown strong activity against human xenograft lung, colon, pancreatic, ovarian and breast tumors in nude rat models. Methods: This is a first-in-human study of IMGN388. New cohorts of patients with advanced solid tumors receive increasing doses of IMGN388, given intravenously, to establish its maximum tolerated dose (MTD). The primary study objectives are to evaluate the safety, MTD and pharmacokinetics (PK) of IMGN388 when given every 3 weeks. Secondary objectives include evaluation of pharmacodynamics, immunogenicity and evidence of activity. Results: 26 patients received a total of 52 cycles of IMGN388 at doses ranging from 5 to 80 mg/m2. IMGN388 was generally well-tolerated. Grade 1/2 toxicities assessed to be treatment related include: fatigue, nausea, anorexia, vomiting, diarrhea, headache and allergic reaction. One dose-limiting toxicity was seen, which was grade 3 headache and confusion 24 hours after the first infusion of IMGN388 at a dose of 45 mg/m2. Prophylactic steroid administration was implemented and no further events have occurred. There has been no evidence of human anti-human antibody formation (data available for doses up to 60 mg/m2). Preliminary IMGN388 PK findings reveal an elimination phase half-life of approximately 28 hours; maximal plasma concentration increases in a generally dose-proportional manner. No evidence of activity was observed at the lowest doses evaluated. At 45 mg/m2, a patient with non-small cell lung carcinoma who previously progressed on two lines of therapy within one year remained on IMGN388 for 6 cycles (18 weeks). Conclusions: IMGN388 has been well tolerated at the doses tested, demonstrating initial evidence of safety in early clinical phase I testing. The MTD has not yet been defined and the study is ongoing. Updated results will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ImmunoGen ImmunoGen