Safety and efficacy of CDX-014, an antibody-drug conjugate directed against T cell immunoglobulin mucin-1 in advanced re
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PHASE I STUDIES
Safety and efficacy of CDX-014, an antibody-drug conjugate directed against T cell immunoglobulin mucin-1 in advanced renal cell carcinoma Bradley A. McGregor 1 & Michael Gordon 2 & Ronan Flippot 1 & Neeraj Agarwal 3 & Saby George 4 David I. Quinn 5 & Mark Rogalski 6 & Thomas Hawthorne 6 & Tibor Keler 6 & Toni K. Choueiri 1
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Received: 8 April 2020 / Accepted: 6 May 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Summary CDX-014 is an antibody-drug conjugate directed against TIM-1, a surface marker highly expressed in renal cell carcinoma (RCC) and ovarian carcinoma. This phase I, first-in-human trial was conducted to evaluate the safety and preliminary activity of CDX-014 in patients with advanced refractory RCC, following a dose-escalation and dose expansion design. CDX-014 was administered intravenously at doses ranging from 0.15 to 2.0 mg/kg every 2 or 3 weeks until progression or unacceptable toxicity. Sixteen patients received at least one dose of CDX-014. The maximum tolerated dose was not identified. Most frequent adverse grade 1 or 2 adverse events included nausea (38%), fatigue, alopecia, elevation of AST and decreased appetite (25% each). Adverse events of grade 3 or more included hyperglycemia (19%), urosepsis (6%), and one multi-organ failure (6%) responsible for one treatment-related death. Two patients discontinued therapy for adverse events including fatigue grade 2 and urosepsis grade 4. CDX-014 showed antitumor activity with one prolonged partial response and a clinical benefit rate (objective response or stable disease >6 months) of 31%. The two patients that exhibited the most marked tumor shrinkage had high TIM-1 expression on tumor tissue. Overall, CDX-014 exhibited a manageable toxicity profile and early signs of activity, supporting further evaluation of antibody-drug conjugates in patients with advanced RCC and potentially other TIM-1 expressing cancers. Trial registration https://clinicaltrials.gov/ct2/show/NCT02837991 NCT02837991; July 20, 2016. Keywords Renal cell carcinoma . Antibody-drug conjugate . Phase 1 trial . Salvage therapy . First-in-human . Metastatic renal cell carcinoma
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10637-020-00945-y) contains supplementary material, which is available to authorized users. * Toni K. Choueiri [email protected] 1
Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, Boston, MA, USA
2
HonorHealth Research Institute, Scottsdale, AZ, USA
3
University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA
4
Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
5
University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
6
Celldex Therapeutics, Inc., Hampton, NJ, USA
Outcomes of patients with renal cell carcinoma (RCC) have improved since the advent of antiangiogenic therapies and immune checkpoint inhibitors; with combinations of immunotherapies alone or with v
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