Journal article
131I-LNTH-1095 Radioligand Therapy Plus Enzalutamide vs. Enzalutamide Alone in Men With PSMA-Avid Metastatic Castration-Resistant Prostate Cancer: A Phase 2 Study
Clinical cancer research, Vol.32(10), pp.1973-1982
05/15/2026
DOI: 10.1158/1078-0432.CCR-25-4948
PMCID: PMC13176818
PMID: 41779000
Abstract
Purpose: The phase 2 ARROW study was designed to evaluate radioligand therapy with 131I-LNTH-1095, an iodine-131–labeled small molecule targeting PSMA, in combination with enzalutamide in subjects with metastatic castration-resistant prostate cancer after progression on prior abiraterone therapy. Patients and Methods: Men ≥18 years with PSMA-positive prostate cancer (PSMA PET tracer uptake >1× liver SUVmean in all CT-measurable lesions) were randomized 2:1 to 131I-LNTH-1095 (4 cycles of 3.7 GBq/dose every 8 weeks)+enzalutamide (160 mg po qd) vs. enzalutamide alone. The primary endpoint was PSA50 response. Secondary endpoints included rPFS, ORR, OS, and safety. Results: Of 177 screened subjects, 120 were randomized (80: 131I-LNTH-1095+enzalutamide; 40: enzalutamide-monotherapy). PSA50 response was 62.9% (95% CI, 50.5-74.1) for 131I-LNTH-1095+enzalutamide vs. 31.3% (16.1-50.0) for enzalutamide alone (P=.003). Median rPFS was 14.0 months (95% CI: 8.64-18.20) for 131I-LNTH-1095+enzalutamide vs. 11.5 months (2.79–18.43) for enzalutamide alone (P=.10). Incidence of grade ≥3 treatment-emergent adverse events (TEAEs) was 65.8% for 131I-095+enzalutamide vs. 41.0% for enzalutamide-monotherapy; the most frequent TEAEs were fatigue (75.0 vs. 53.8%), nausea (59.2 vs. 33.3%), thrombocytopenia (51.3 vs. 0%), and decreased appetite (48.7 vs. 17.9%), respectively. Two deaths in the 131I-LNTH-1095+enzalutamide group were considered treatment-related. The study was not powered to detect rPFS and OS differences. Conclusions: 131I-LNTH-1095+enzalutamide was associated with a statistically significant improvement in PSA50 response compared to enzalutamide alone despite a lower dosing schedule (4 cycles of 3.7 GBq/dose every 8 weeks) than the other approved PSMA RLT agents. Grade ≥3 adverse events were more frequent with combination therapy, particularly hematologic toxicity. NCT03939689
Details
- Title: Subtitle
- 131I-LNTH-1095 Radioligand Therapy Plus Enzalutamide vs. Enzalutamide Alone in Men With PSMA-Avid Metastatic Castration-Resistant Prostate Cancer: A Phase 2 Study
- Creators
- Evan Y Yu - Fred Hutch Cancer CenterVivek Narayan - University of PennsylvaniaGiuseppe Esposito - Georgetown UniversityRussell Szmulewitz - University of ChicagoYang Lu - The University of Texas MD Anderson Cancer CenterMichael B Lilly - Medical University of South CarolinaJeremie Calais - University of California, Los AngelesGennady Bratslavsky - SUNY Upstate Medical UniversityYusuf Menda - University of Iowa Hospitals and ClinicsMinal Vasanawala - VA Palo Alto Health Care SystemFrédéric Pouliot - Centre hospitalier de l'Université LavalDavid Laidley - London Health Sciences CentreNeil Fleshner - Princess Margaret Cancer CentreFred Saad - Centre Hospitalier de l’Université de MontréalJean-Claude Provost - Bedford Research FoundationIryna Teslenko - Universidad Nacional de LanúsNand Kishore Rawat - Universidad Nacional de LanúsGary Ulaner - Hoag Memorial Hospital Presbyterian
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.32(10), pp.1973-1982
- DOI
- 10.1158/1078-0432.CCR-25-4948
- PMID
- 41779000
- PMCID
- PMC13176818
- NLM abbreviation
- Clin Cancer Res
- ISSN
- 1557-3265
- eISSN
- 1557-3265
- Publisher
- AMER ASSOC CANCER RESEARCH
- Grant note
- Progenics Pharmaceuticals Inc. Lantheus company
The sponsor of this trial was Progenics Pharmaceuticals Inc., a Lantheus company. Medical writing support was provided by Laurie Thomas of Winfield Consulting and April Teitelbaum, MD; Vincent A. DiPippo, PhD; Saradha Baskaran, PhD; and Nancy Stambler, DrPH, of Lantheus. Angel Koo, Michelle Dionne, and Matt Mockler of Lantheus provided important operational support. The authors thank the study participants and participating centers, including the University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; University of Pennsylvania, Philadelphia, PA; MedStar Georgetown University Hospital, Washington, DC; University of Chicago Medical Center Duchossois Center for Advanced Medicine, Chicago, IL; Washington University School of Medicine, St. Louis, MO; City of Hope Duarte Cancer Center, Duarte, CA; University of Virginia Cancer Center, Charlottesville, VA; University of Texas MD Anderson Cancer Center, Houston, TX; University of Washington, Seattle, WA; Medical University of South Carolina Hollings Cancer Center, Charleston, SC; University of Maryland, Baltimore, MD; University of California Los Angeles, Los Angeles, CA; SUNY Upstate Medical University, Syracuse, NY; University of Iowa, Iowa City, IA; VA Palo Alto Healthcare System, Palo Alto, CA; Hoag Family Cancer Institute (Hoag Memorial Hospital Presbyterian), Newport Beach, CA; Jewish General Hospital, Montreal, QC; Centre Hospitalier Universitaire de Quebec, Universite Laval, L'Hotel-Dieu de Quebec, Quebec, QC; Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC; London Health Sciences Centre, London, ON; University Health Network, Princess Margaret Cancer Centre, Toronto, ON; Centre Hospitalier de l'Universite de Montreal, Montreal, QC; and The Ottawa Hospital, Ottawa, ON.
- Language
- English
- Electronic publication date
- 03/04/2026
- Date published
- 05/15/2026
- Academic Unit
- Radiology; Radiation Oncology
- Record Identifier
- 9985141897402771
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