Abstract Integrin beta-6 (ITGb6) is a heterodimeric, cell-surface glycoprotein highly expressed in multiple solid tumor indications, including non-small cell lung cancer, esophageal cancer, head and neck cancers, breast and gastric cancers. Its expression has been associated with pro-tumorigenic activities including proliferation, migration, and invasion. ITGb6 has restricted expression in adult tissues, making it a highly promising target for cancer therapy using antibody drug conjugates (ADCs). STRO-006 is an investigational ADC composed of an ITGb6 targeted human IgG1 antibody conjugated to exatecan, a topoisomerase 1 inhibitor, via a b-glucuronidase-cleavable linker. The anti-ITGb6 antibody was discovered from a Fab ribosome display library using Sutro’s XpressCF+® system. The drug-linker is functionalized with dibenzylcyclooctyne (DBCO) and allows rapid and selective site-specific conjugation to the azide-containing non-natural amino acid p-azidomethylphenylalanine (pAMF) incorporated into the antibody (Ab) sequence using XpressCF+®. This site-specific conjugation is highly efficient, resulting in a well-defined, homogeneous ADC with a drug-antibody ratio (DAR) of 8. The STRO-006 antibody binds specifically to the alpha-v beta-6 heterodimer and has high affinity to human and cynomolgus ITGb6. It demonstrates rapid and efficient internalization, ideal for an ADC mechanism of action. Importantly, the STRO-006 antibody does not compete for LAP binding and therefore does not interfere with TGFb signaling. STRO-006 is optimized for a stable pharmacokinetic profile and exhibits extended half-life of ∼7 days, low clearance of ∼5 mL/d/kg and maintains a stable DAR over the course of 21-days in non-human primates. In preclinical studies, STRO-006 demonstrates potent anti-tumor activity at clinically relevant dose in both PDX and xenograft models of non-small cell lung, head and neck squamous cell and pancreatic carcinomas. STRO-006 demonstrates a favorable safety and pharmacokinetic profile in non-human primates. These results suggest that STRO-006 is a promising candidate for the treatment of multiple carcinomas and supports further clinical investigation. A Phase 1, first-in-human study is planned to assess the safety and activity of STRO-006. Citation Format: Kshama A. Doshi, Stephanie Armstrong, Eunice Kim, Dan Shen, Sihong Zhou, Rhoneil Pena, Robert Yuan, Mark Armanini, Brian Vuillemenot, Xiaofan Li, Guifen Xu, Krishna Bajjuri, Miao Wen, Jeff Hanson, Cuong Tran, Amandeep Gakhal, GARRETT GROSS, Gang Yin, Werner Rubas, Genevive Hernandez, Daniel Calarese, Hans-Peter Gerber, Alice Yam. STRO-006: An Integrin beta-6-targeting ADC demonstrates favorable safety profile and potent antitumor activity in preclinical solid tumors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1713.
Doshi et al. (Fri,) studied this question.