Abstract CT073: FiREBOLT: A phase 1 study evaluating radioligand therapy with LY4337713 in adults with select FAP+ solid tumors (Trial in progress)

Abstract Background: Fibroblast activation protein (FAP) is a transmembrane glycoprotein highly expressed on cancer-associated fibroblasts in tumor stroma but minimally expressed in normal adult tissues1. FAP-targeted imaging radioligands have shown high rates of positivity across a wide range of cancers. However, first-generation FAP-targeting therapeutic radioligands have been limited by rapid tumor washout, resulting in low absorbed doses and limited efficacy. LY4337713 is a next-generation FAP-targeting radioligand therapy labeled with Lu-177 that demonstrated high tumor retention, for at least up to 144 hours2, while maintaining rapid normal organ clearance in preclinical studies and in a clinical imaging study. Methods: FiREBOLT is a phase 1a/1b, open-label, multicenter study of LY4337713 in participants (pts) with select FAP+ advanced/metastatic solid tumors (NCT07213791), specifically breast cancer (HR+/HER2-, HER2+, triple-negative [TNBC]), pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), cholangiocarcinoma (CCC), ovarian, gastric, or esophageal cancers. Eligible pts must have RECIST measurable disease and FAP uptake confirmed by imaging. Prior lines of therapy allowed are outlined in the Table. Phase 1a dose escalation will assess safety and tolerability of LY4337713 monotherapy. The dose-limiting toxicity (DLT) monitoring period will be 28 days and the modified toxicity probability interval-2 (mTPI-2) statistical model will guide dose decisions to determine the maximum tolerated dose (MTD) or the highest tested dose deemed safe. Previously cleared dose levels with therapeutically relevant exposures or direct evidence of clinical activity will permit backfills. In dose optimization, pts will be randomized 1:1 between 2-3 dose regimens of LY4337713 to determine the optimal dose level and schedule. Phase 1b dose expansion will assess antitumor efficacy per RECIST 1.1 in tumor-specific cohorts. Additional secondary and exploratory objectives in the study include assessing PK, biodistribution, and radiation dosimetry of LY4337713.Table1Fitzgerald A, et al. Cancer Metastasis Rev. 2020, 39(3):783-803 2Kaoma C, et al. JNM. 2025, 66(1):251266 Citation Format: Gary A. Ulaner, Shadi Esfahani, Joyce O'Shaughnessy, Andrei Iagaru, Dejan Juric, Vikas Prasad, Anthony F. Shields, Aman Opneja, Arthur J.A.T Braat, Wolfgang P. Fendler, Jian Liu, Richard Cioci, Issraa Shoucair, Frankis Almaguel. FiREBOLT: A phase 1 study evaluating radioligand therapy with LY4337713 in adults with select FAP+ solid tumors (Trial in progress) [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 CT073.