SGN-B6A: A New Vedotin Antibody-Drug Conjugate Directed to Integrin Beta-6 for Multiple Carcinoma Indications

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Abstract

Integrin beta-6, a component of the heterodimeric adhesion receptor alpha-v/beta-6, is overexpressed in numerous solid tumors. Its expression has been shown by multiple investigators to be a negative prognostic indicator in diverse cancers including colorectal, non-small cell lung, gastric, and cervical. We developed SGNB6A as an antibody-drug conjugate (ADC) directed to integrin beta-6 to deliver the clinically validated payload monomethyl auristatin E (MMAE) to cancer cells. The antibody component of SGN-B6A is specific for integrin beta-6 and does not bind other alpha-v family members. In preclinical studies, this ADC has demonstrated activity in vivo in models derived from non-small cell lung, pancreatic, pharyngeal, and bladder carcinomas spanning a range of antigen expression levels. In nonclinical toxicology studies in cynomolgus monkeys, doses of up to 5 mg/kg weekly for four doses or 6 mg/kg every 3 weeks for two doses were tolerated. Hematologic toxicities typical of MMAE ADCs were dose limiting, and no significant target-mediated toxicity was observed. A phase I first-in-human study is in progress to evaluate the safety and antitumor activity of SGN-B6A in a variety of solid tumors known to express integrin beta-6 (NCT04389632).

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APA

Lyon, R. P., Jonas, M., Frantz, C., Trueblood, E. S., Yumul, R., Westendorf, L., … Ryan, M. C. (2023). SGN-B6A: A New Vedotin Antibody-Drug Conjugate Directed to Integrin Beta-6 for Multiple Carcinoma Indications. Molecular Cancer Therapeutics, 22(12), 1444–1453. https://doi.org/10.1158/1535-7163.MCT-22-0817

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