Abstract
Once-daily oral paltusotine in the treatment of patients with carcinoid syndrome: Biomarker analysis results from a phase 2, randomized, parallel-group study
Journal of clinical oncology, Vol.44(2_suppl), pp.632-632
01/10/2026
DOI: 10.1200/JCO.2026.44.2_suppl.632
Abstract
632 Background: Paltusotine is an oral, nonpeptide, selective somatostatin receptor 2 agonist. In a phase 2 study, treatment with once-daily paltusotine reduced the frequency and severity of carcinoid syndrome (CS) symptoms and was well tolerated. The effect of paltusotine on biomarkers of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) was further explored. Methods: This exploratory study, without formal power calculations, included an 8-week randomized treatment phase (completed) and a 102-week open-label extension phase (currently ongoing). The purpose was to evaluate safety, pharmacokinetics, and exploratory efficacy endpoints, including changes in biomarkers of paltusotine treatment. Enrolled patients were adults with a stable, documented grade 1 or 2 neuroendocrine tumor (NET) and CS. These patients were actively symptomatic and either untreated with somatostatin receptor ligand (SRL) therapy (average of ≥4 bowel movements [BMs] per day or >2 flushing episodes per day in ≥2 days over a 2-week period) or washed out of SRL therapy (symptoms previously controlled on SRL), with demonstrated symptom worsening after washout. Patients were randomized to once-daily paltusotine 40 mg or 80 mg; one optional uptitration (from 40 mg to 80 mg or 80 mg to 120 mg) was permitted. Blood samples for assessment of biomarkers (serum serotonin and plasma 5-HIAA) were collected longitudinally from screening to end of treatment. Upper limit of normal was prespecified as 541 ng/mL for serotonin and 22 ng/mL for 5-HIAA. This analysis focuses on changes in biomarker from baseline to the end of 8-week randomized treatment phase and after approximately one year (48 weeks). Results: Thirty-six patients (n=9 untreated; n=27 SRL washout) were randomized. Mean age was 60.8 years (range 35-83), and 52.8% were female. Nineteen patients had grade 1 NETs, and 17 had grade 2 NETs. As reported previously, treatment with once-daily, oral paltusotine was well tolerated and reduced the frequency and severity of CS symptoms, justifying further clinical development of the 80 mg dose. Mean serum serotonin decreased from 1553.0 ng/mL at baseline to 643.9 ng/mL at Week 8, and mean plasma 5-HIAA decreased from 245.1 ng/mL to 159.7 ng/mL. There was a trend of untreated patients achieving a greater reduction in comparison to washout patients. At 48-week follow-up, mean serum serotonin was stabilized at 791.50 ng/mL (n=20), and mean plasma 5-HIAA was stabilized at 190.45 ng/mL (n=20). Conclusions: Paltusotine significantly reduced serotonin and 5-HIAA levels, with effects maintained at 48 weeks. Biomarker reductions paralleled reductions in BM and flushing frequency. These findings support further investigation in the ongoing phase 3 study (CAREFNDR, NCT07087054). Clinical trial information: NCT05361668 .
Details
- Title: Subtitle
- Once-daily oral paltusotine in the treatment of patients with carcinoid syndrome: Biomarker analysis results from a phase 2, randomized, parallel-group study
- Creators
- Ana Isabel Oviedo AlborAmr Mohamed - Case Western Reserve UniversityRachel Riechelmann - AC Camargo HospitalJuan Manuel O'ConnorMary Alice Maluccio - Louisiana State University Health Sciences Center New OrleansSimron Singh - Sunnybrook Health Science CentreLukasz Hajac - European Neuroendocrine Tumor SocietyMichael J. Demeure - Hoag Memorial Hospital PresbyterianJoseph S. Dillon - University of IowaShagufta ShaheenJuliana Lorenzoni Althoff - Hospital São PauloMariano Dioca Dioca - Instituto de Oncología de RosarioThorvardur Ragnar HalfdanarsonAndrew Hendifar - Cedars-Sinai Medical CenterAna Rosa Pinto Quidute - Universidade Federal do CearáMariana Scandizzo - Hospital Universitario AustralDenka Markova - Crinetics PharmaceuticalsZhimin Xiao - Crinetics PharmaceuticalsAman Chauhan - Sylvester Comprehensive Cancer CenterLowell Brian Anthony - University of Kentucky
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.44(2_suppl), pp.632-632
- DOI
- 10.1200/JCO.2026.44.2_suppl.632
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Publisher
- American Society of Clinical Oncology
- Language
- English
- Date published
- 01/10/2026
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9985121481902771
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