ECE2024 Poster Presentations Endocrine-Related Cancer (40 abstracts)
Once-daily oral paltusotine in the treatment of patients with carcinoid syndrome: interim results from a phase 2, randomized, parallel-group study
Aman Chauhan 1 , Amr Mohamed 2 , Keith Usiskin 3 , Cosina Mui 3 , Joseph Dillon 4 , Xiaolin Fan 3 , Shagufta Shaheen 5 , Juan Manuel O’Connor 6 , Simron Singh 7 , Hjalmar Lagast 3 & Alan Krasner 3
1University of Kentucky Healthcare, Lexington, USA; 2University Hospital, Case Western Reserve University, Cleveland, USA; 3Crinetics Pharmaceuticals, San Diego, USA; 4University of Iowa, Carver College of Medicine, Iowa City, USA; 5Stanford Medicine, Stanford, USA; 6Instituto Alexander Fleming, Buenos Aires, Argentina; 7Sunnybrook Health Sciences Center, Toronto, Canada
Background: Carcinoid syndrome (CS), the most common functional neuroendocrine tumor (NET) syndrome, is characterized by watery diarrhea or cutaneous flushing. While somatostatin receptor ligand (SRL) depot injections are mainstay treatments for CS, discomfort with injections and inadequate symptom relief at labeled doses are seen with many patients. Paltusotine is an investigational once-daily, oral, selective SST2 agonist in development for the treatment of acromegaly and CS. In patients with acromegaly, paltusotine has been shown to maintain IGF-I control at levels similar to those for injected depot SRLs.
Methods: This ongoing open-label, multicenter study examines the safety, tolerability, pharmacokinetics, and exploratory efficacy of paltusotine in the treatment of patients with CS. Eligible patients had documented, well-differentiated, grade I or II NETs with CS. Patients who were actively symptomatic (average of ≥4 BMs per day or >2 flushing episodes per day in ≥2 days over a 2-week period) and naïve to SRL therapy, or patients with symptom control on SRLs and demonstrated symptom worsening after SRL washout, were randomly assigned to receive 40 mg or 80 mg of once-daily oral paltusotine for 8 weeks. Safety assessments included adverse event (AE) monitoring, clinical laboratory tests, physical examinations, vital signs, and electrocardiograms. Exploratory efficacy was assessed using a daily electronic symptom diary.
Results: This interim analysis includes 16 patients who received paltusotine and had been in the study long enough to complete the randomized treatment period. Mean age was 61 years; 56% of patients were female. Six patients were naïve to SRL therapy and 10 were previously controlled on SRLs. Four patients met the entry criteria for flushing only, 6 for BM only, and 6 for both. One patient discontinued prior to the end of randomized treatment. At Week 8, mean reduction from baseline in daily BM frequency was −1.3 and in daily flushing frequency was −2.2. Mean decrease in daily frequency of urgent BM episodes was −0.6; mean decrease in flushing severity (worst flushing score, rated on a scale from 0 to 10) was −2.9. Four patients had their paltusotine dose increased during the randomized treatment period. There were no serious AEs considered related to study treatment and no AEs leading to discontinuation. No new safety signals were identified.
Conclusions: Interim data from this phase 2 study suggest that oral paltusotine controls the symptoms of CS and is well tolerated.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more