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Cancer Chemother Pharmacol. 2016 Jan;77(1):155-62. doi: 10.1007/s00280-015-2909-2. Epub 2015 Nov 14.

First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70.

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Department of Hematology/Medical Oncology, The Winship Cancer Institute of Emory University, 1365 Clifton Road, NE, Atlanta, GA, 30322, USA.
University of Maryland Cancer Center, Baltimore, MD, USA.
The University of Chicago Medicine and Biological Sciences, Chicago, IL, USA.
University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
Yale University, New Haven, CT, USA.
Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Bristol-Myers Squibb, New York, NY, USA.



The study evaluated the safety, tolerability, and pharmacokinetics of BMS-936561, a fully human monoclonal antibody-drug conjugate targeting CD70 cell-surface protein.


Eligible patients had ECOG performance status 0-2 and received ≤3 prior chemotherapy regimens. An initial accelerated titration design enrolling one patient per dose level was followed by 3 + 3 dose escalation with the first observation of a grade ≥2 adverse event (AE). We tested escalating doses of BMS-936561 (0.5, 1, 2, 4, 8, 15 mg/kg) administered every 21 days in a 42 day cycle for a maximum of 17 cycles. Pharmacokinetic samples were collected in cycle 1.


A total of 26 patients enrolled; 16 and 10 for the escalation and expansion cohorts, respectively. Median age was 63 years (48-74); 18 males and 25 Caucasians. There was no defined MTD per protocol, but a DLT of grade 3 hypersensitivity was recorded in 2 of 16 (13%) subjects at the highest dose of 15 mg/kg. The most frequent AEs were: fatigue (85%), nausea (54%), and decreased appetite (39%). Delayed toxicities (facial edema and pleural/pericardial effusions) occurred in 6 of 16 (38%) subjects at the 15 mg/kg dose. PK analysis showed a dose-proportional increase in active drug levels with increasing doses. There was disease stabilization in 18 of 26 patients (69%) without correlation with received dose.


BMS-936561 is well tolerated over a wide range of doses in patients with advanced ccRCC and B-NHL. The 8 mg/kg dose was the highest best tolerated dose and the recommended dose for future studies.


Antibody-drug conjugate; BMS-936561; CD70; Pharmacokinetic; Phase

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