Abstract CT077: STRO-004 ST1: Phase 1 open-label study to evaluate safety, pharmacokinetics, and preliminary anti-tumor activity of STRO-004 in adults with refractory/recurrent metastatic solid tumors

Abstract Background: The treatment of recurrent or metastatic solid tumors remains a challenge, particularly in patients with relapsed disease following standard-of-care treatment. Tissue Factor (TF), a transmembrane glycoprotein with tumor-selective expression, has been implicated in promoting tumor progression through enhanced tumor angiogenesis and metastasis, making it an ideal target for an antibody-drug conjugate (ADC) (Li et al, 2022). TF is overexpressed on the cell surface of multiple solid tumors, including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), cervical, colorectal cancer (CRC), and pancreatic cancer (PDAC) (de Bono et al, 2022). STRO-004 is a novel TF-targeted ADC incorporating a site-specific beta-glucuronidase-cleavable, stable linker and an exatecan payload, with a drug-antibody ratio (DAR)=8. STRO-004 is engineered for enhanced plasma stability and pharmacokinetics (PK), leading to improved efficacy and reduced off-target toxicity compared with 1st generation TF ADCs. Preclinical data demonstrate potent anti-tumor activity across TF-expressing tumor models, including those with heterogenous or low TF expression. Upon binding to TF, STRO-004 undergoes receptor mediated internalization, releasing its exatecan payload within the lysosome. The membrane-permeable nature of exatecan enables diffusion into adjacent TF-negative cells, resulting in bystander killing. STRO-004 also induces immunogenic cell death (ICD), activating antigen-presenting cells (APCs) and potentially driving durable anti-tumor immunity. These findings support combination with immunotherapies. Methods: STRO-004-ST1 is a first-in-human, Phase 1, open-label, multicenter study evaluating the safety, PK, and anti-tumor activity of STRO-004 in adults with refractory or recurrent metastatic solid tumors. The trial includes three parts: Monotherapy Dose Escalation (Part 1A), Monotherapy Cohort Expansion (Part 1B) and Combination Dose Escalation with pembrolizumab (Part 1C). Eligible patients are adults (≥ 18 years) with previously treated HNSCC, NSCLC, esophageal, gastric, PDAC, CRC, endometrial, cervical or urothelial cancer who have measurable disease and tissue available for retrospective central testing. STRO-004 is administered intravenously every 3 weeks.Part 1A endpoints include maximum tolerated dose (MTD), dose-limiting toxicity (DLT), anti-tumor activity and PK; efficacy is the primary endpoint in Part 1B. Approximately 200 patients will be enrolled. The study (NCT07227168) is open and enrolling at time of submission. Citation Format: David Sommerhalder, Joshua Reuss, Leontios Pappas, Mohamad A. Salkeni, Andrae Vandross, Jason T. Henry, Genevive Hernandez, Milan Mangeshkar, Jennifer Oliver, Manish R. Patel. STRO-004 ST1: Phase 1 open-label study to evaluate safety, pharmacokinetics, and preliminary anti-tumor activity of STRO-004 in adults with refractory/recurrent metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT077.