In:
Investigational New Drugs, Springer Science and Business Media LLC, Vol. 34, No. 3 ( 2016-06), p. 290-299
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.
Type of Medium:
Online Resource
ISSN:
0167-6997
,
1573-0646
DOI:
10.1007/s10637-016-0336-9
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2016
detail.hit.zdb_id:
2009846-7
SSG:
15,3
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