Abstract CT196: Phase 1 dose escalation and expansion study of the PTK7-targeted antibody-drug conjugate DAY301 in patients with locally advanced or metastatic solid tumors

Abstract Background: PTK7 (protein tyrosine kinase 7) is a single-pass transmembrane receptor with an inactive intracellular tyrosine kinase domain that is involved in Wnt and VEGFR signaling pathways. It is overexpressed in a wide range of solid tumors, including non-small cell lung cancer, ovarian cancer, and triple-negative breast cancer, and expression has been correlated with poor prognosis and worse survival. The antibody-drug conjugate DAY301 is a humanized PTK7 monoclonal antibody, conjugated through a highly stable valine-alanine cleavable linker to the topoisomerase I inhibitor, exatecan. The drug-to-antibody ratio is 8. DAY301 has demonstrated potent antitumor activity in wide range of tumor xenograft models in vivo, with cytotoxic activity achieved through DNA damage and apoptosis induction, as well as a strong bystander effect. Methods: NCT06752681 is an ongoing first-in-human phase 1a/1b, open-label, dose escalation, and expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of DAY301. Patients aged ≥18 years with an advanced or metastatic solid tumor, an Eastern Cooperative Oncology Group performance status of 0 or 1, measurable disease per RECIST 1.1, an available tumor tissue sample, and adequate organ function are eligible. DAY301 is administered intravenously once every 3 weeks. The primary objectives of part 1a are to characterize the safety and tolerability of DAY301, and to establish the maximum tolerated dose and recommended dose for expansion cohorts. The dose-limiting toxicity evaluation period is 21 days after the initial dose. Patients may also be enrolled in backfill cohorts to further characterize safety, PK, and preliminary efficacy at previously cleared dose levels. Dose escalation will utilize a Bayesian optimal interval design, except for the first dose cohort where an accelerated titration design will enroll 1 patient initially. In phase 1b, DAY301 will be evaluated in up to 4 tumor-specific dose expansion cohorts in patients with advanced solid tumors. The primary objectives of phase 1b are to evaluate preliminary efficacy of DAY301 as assessed by overall response rate and to further evaluate safety. Based on the totality of data from phase 1b, a recommended phase 2 dose for future clinical studies will be determined. Recruitment for the trial started in December 2024, with the aim of a maximum of 84 patients to be enrolled in phase 1a and 116 patients in phase 1b. Citation Format: David Sommerhalder, Gregory A. Durm, Robert Maki, Patricia M. LoRusso, Sarina A. Piha-Paul, Philippe L. Bedard, Nicole Chau, Eleni Venetsanakos, Stephanie Hume, Jiaheng Qiu, Michele Martorana, Mark W. Kieran, Daniel Da Costa, Nehal Lakhani. Phase 1 dose escalation and expansion study of the PTK7-targeted antibody-drug conjugate DAY301 in patients with locally advanced or metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT196.