Safety and efficacy of CDX-014, an antibody-drug conjugate directed against T cell immunoglobulin mucin-1 in advanced renal cell carcinoma.

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 NCT02837991; July 20, 2016.

Investigational new drugs. 2020 May 29 [Epub ahead of print]

Bradley A McGregor, Michael Gordon, Ronan Flippot, Neeraj Agarwal, Saby George, David I Quinn, Mark Rogalski, Thomas Hawthorne, Tibor Keler, Toni K Choueiri

Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, Boston, MA, USA., HonorHealth Research Institute, Scottsdale, AZ, USA., University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA., Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA., Celldex Therapeutics, Inc., Hampton, NJ, USA., Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, Boston, MA, USA. .