title: Phase I study of IMGN901, a CD56-targeting antibody-drug conjugate, in patients with CD56-positive solid tumors.
abstract: Background IMGN901 is a CD56-targeting antibody-drug conjugate designed for tumor-selective delivery of the cytotoxic maytansinoid DM1. This phase 1 study investigated the safety, tolerability, pharmacokinetics, and preliminary activity of IMGN901 in patients with CD56-expressing solid tumors. Methods Patients were enrolled in cohorts of escalating IMGN901 doses, administered intravenously, on 3 consecutive days every 21 days. A dose-expansion phase accrued patients with small cell lung cancer (SCLC), Merkel cell carcinoma (MCC), or ovarian cancer. Results Fifty-two patients were treated at doses escalating from 4 to 94 mg/m(2)/day. The maximum tolerated dose (MTD) was determined to be 75 mg/m(2). Dose-limiting toxicities included fatigue, neuropathy, headache or meningitis-like symptoms, chest pain, dyspnea, and myalgias. In the dose-expansion phase (n = 45), seven patients received 75 mg/m(2) and 38 received 60 mg/m(2) for up to 21 cycles. The recommended phase 2 dose (RP2D) was established at 60 mg/m(2) during dose expansion. Overall, treatment-emergent adverse events (TEAEs) were experienced by 96.9 % of all patients, the majority of which were Grade 1 or 2. The most commonly reported Grade 3 or 4 TEAEs were hyponatremia and dyspnea (each 8.2 %). Responses included 1 complete response (CR), 1 clinical CR, and 1 unconfirmed partial response (PR) in MCC; and 1 unconfirmed PR in SCLC. Stable disease was seen for 25 % of all evaluable patients who received doses ≥60 mg/m(2). Conclusions The RP2D for IMGN901 of 60 mg/m(2) administered for 3 consecutive days every 3 weeks was associated with an acceptable tolerability profile. Objective responses were observed in patients with advanced CD56+ cancers.
authors.affiliation: Ohio State University College of Medicine, Columbus, OH, 43210, USA.
authors.forename: Manisha H
authors.initials: MH
authors.lastname: Shah
authors.affiliation: University of Manchester/Christie NHS Foundation Trust, Manchester, M20 4BX, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Lorigan
authors.affiliation: Royal Marsden Hospital, Sutton, Surrey, SM2 5PT, UK.
authors.forename: Mary E R
authors.initials: ME
authors.lastname: O'Brien
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Frank V
authors.initials: FV
authors.lastname: Fossella
authors.affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
authors.forename: Kathleen N
authors.initials: KN
authors.lastname: Moore
authors.affiliation: Department of Medicine, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
authors.forename: Shailender
authors.initials: S
authors.lastname: Bhatia
authors.affiliation: ImmunoGen, Inc., Waltham, MA, 02451, USA.
authors.forename: Maurice
authors.initials: M
authors.lastname: Kirby
authors.affiliation: Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield, Whitham Road, Sheffield, S10 2SJ, UK. p.j.woll@sheffield.ac.uk.
authors.forename: Penella J
authors.initials: PJ
authors.lastname: Woll
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000074322:Antineoplastic Agents, Immunological / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D019002:CD56 Antigen / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008453:Maytansine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000074322:Antineoplastic Agents, Immunological; D019002:CD56 Antigen; C579429:lorvotuzumab mertansine; D008453:Maytansine
keywords: Antibody-drug conjugate; CD56; DM1; IMGN901; Lorvotuzumab mertansine