FiREBOLT: A phase 1 study evaluating radioligand therapy with LY4337713 in adults with select FAP+ solid tumors (Trial in progress)
Presenter: Gary Ulaner Session: Phase I Clinical Trials in Progress Time: 4/20/2026 9:00:00 AM → 4/20/2026 12:00:00 PM
Authors
Gary A. Ulaner 1 , Shadi Esfahani 2 , Joyce O’Shaughnessy 3 , Andrei Iagaru 4 , Dejan Juric 5 , Vikas Prasad 6 , Anthony F. Shields 7 , Aman Opneja 8 , Arthur J.A.T Braat 9 , Wolfgang P. Fendler 10 , Jian Liu 11 , Richard Cioci 11 , Issraa Shoucair 11 , Frankis Almaguel 12 1 Hoag Family Cancer Institute and University of Southern California, Irvine, Los Angeles, CA, 2 Massachusetts General Hospital, Boston, MA, 3 Texas Oncology, Dallas, TX, 4 Stanford University, Standford, CA, 5 Termeer Center for Targeted Therapies, Massachusetts General Hospital Cancer Center, Boston, MA, 6 Washington University in St. Louis, St. Louis, MO, 7 Karmanos Cancer Institute, Wayne State University, Detroit, MI, 8 Duke Cancer Institute, Durham, NC, 9 Netherlands Cancer Institute, University Medical Center Utrecht, Amsterdam, Utrecht, Netherlands, 10 Department of Nuclear Medicine, West German Cancer Center, DKTK and NCT site, University Hospital Essen, Essen, Germany, 11 Eli Lilly and Company, Indianapolis, IN, 12 Biogenix Molecular, Miami, FL
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 tissues 1 . 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 hours 2 , 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. Table 1 Fitzgerald A, et al. Cancer Metastasis Rev . 2020, 39(3):783-803 2 Kaoma C, et al. JNM. 2025 , 66(1):251266 Table Phase Tumor Type Prior Therapy Dose Escalation • HR+/HER2- Breast Cancer (BC) • ≤5 prior lines, including CDK4/6 a inhibitor • HER2+ BC • ≥2 HER2 targeted lines, including ≥1 ADC b (if available) • TNBC • ≥2 prior lines for metastatic disease • PDAC • Progressed after 1-2 prior regimens • Ovarian Cancer (platinum resistant or refractory) • ≥1 platinum-based therapy • Other solid tumors (CRC, CCC, gastric, esophageal) • ≥1 prior systemic line (including prior line(s) in combo with immunotherapy or VEGF c inhibitor) Dose Expansion • Advanced or metastatic solid tumors • ≥1 prior line of therapy a CDK 4/6, cyclin-dependent kinase 4/6; b ADC, antibody drug conjugate; c VEGF, vascular endothelial growth factor
Disclosure
G. Ulaner, GE Healthcare; Lantheus Other, Consultant, Scientific Advisory Board member, and Speaker for. Nuclidium; Precirix Other, Consultant, Scientific Advisory Board member for. S. Esfahani, Telix Other, Research Support. Novartis Other, Research Support. SOFIE Other, Research Support. Telix Other, Consult. J. O’Shaughnessy, AADI Bioscience; Agendia; Amgen Biotechnology; Aptitude Health; AstraZeneca; BioNTech; Bristol Myers Squibb; Daiichi Sankyo; Duality; Eisai; Eli Lilly; Ellipses; Exact Sciences; G1 Therapeutics; Gene Other, Consulting Honorarium. A. Iagaru, Alpha9Tx; Clarity Pharmaceuticals; Radionetics Oncology Other, Scientific advisory board fees. GE HealthCare; Novartis Other, Research grants. GE HealthCare; Novartis; Progenics Pharmaceuticals; Telix Other, Consulting fees from. Novartis Other, Roles on scientific steering committees. D. Juric, Roche; Novartis; Eli Lilly; Pfizer; Blueprint; Relay; PIC Therapeutics; Antares Other, Personal fees. Roche; Novartis; Eli Lilly; Pfizer; Blueprint; Arvinas; Takeda; Amgen; Eisai; Syros Other, Research funding (to the institution). V. Prasad, Lilly; ITM; Curium Other, Consult and/ or advisory board. A. Shields, None. A. Opneja, Taiho Oncology Other, Consultancy. Pfizer Consultancy. Astra Zeneca Other, Steering Committee. BurnaAI Other, Advisory board. ShiftMedix Other, Founder. A. Braat, Boston Scientific Other, Consultant. GE Healthcare Other, Consultant. Telix Pharmaceuticals Other, Consultant. Boston Scientific Other, Research support. GE Healthcare Other, Research support. Telix Pharmaceuticals Other, Research support. Ariceum Therapeutics Other, Research support. Siemens Healthineers Other, Research support. W. Fendler, SOFIE Bioscience Other, Research funding. Janssen/JJ Other, consultant, speaker. Perceptive Other, consultant, image review. Bayer Other, consultant, speaker, research funding. Novartis Other, speaker, consultant, research funding. Telix Other, speaker, research funding. GE Healthcare Other, speaker, consultant. Eczacıbaşı Monrol Other, speaker. Abx Other, Speaker. Amgen Other, speaker, research funding. Urotrials Other, speaker. Lilly Other, consultant. AstraZeneca Other, research funding. Curium Other, consultant. J. Liu, Eli Lilly and Company Employment, Stock. R. Cioci, Eli Lilly and Company Employment, Stock. I. Shoucair, Eli Lilly and Company Employment, Stock. F. Almaguel, None.
Cited in
Control: 10123 · Presentation Id: 12170 · Meeting 21436