KEY TAKEAWAYS
- Selinixor is a phase I study that evaluated the safety and efficacy of selinexor in patients with advanced STS.
- Selinixor was given daily for 4 days followed by a break for 3 days. Doses were escalated to find the maximum tolerated dose. Safety, tolerability, anti-tumor activity and PK profile were assessed.
- The study found that selinixor was well-tolerated in sarcoma patients and showed signs of clinical benefit in the form of SD.
Selinexor (S) is a first-in-class drug that can kill cancer cells and effectively treat soft tissue sarcomas (STS). This study aimed to evaluate the safety and efficacy of selinexor in patients with advanced STS.
Researchers assessed Selinexor in patients with advanced metastatic leiomyosarcoma, endometrial stromal sarcoma, and malignant peripheral nerve sheath tumors. Selinexor was given metronomically daily for 4 days, followed by a 3-day break, repeated weekly in a 28-day cycle. Dose levels ranged from 2.5 mg (DL1) to 17.5 mg (DL7), escalated using a 3+3 design to determine the maximum tolerated dose. The primary objectives were safety, tolerability, and recommended phase II dose. Secondary objectives included anti-tumor activity, toxicity profile, and pharmacokinetics (PK) profile. Imaging was done every 8 weeks until unacceptable toxicities or disease progression.
About 25 patients (22 females/3 males, median age 59 years [range 35-84]) were enrolled at different dose levels (3, 3, 4, 6, 6, 3 pts at DL1 to DL6, respectively). The most common adverse events (AE) of any grade were constipation (n = 11, 50%), nausea (n = 11, 50%), and dysgeusia (n = 10, 45%). About 8 (36%) patients experienced Grade 3/4 AE; most were hematological toxicities seen in 3 (14%) patients (anemia, neutropenia, and leukopenia, n = 1 each). Non-hematological Grade 3/4 AE was seen in 5 (23%) patients (including colonic obstruction, atrial fibrillation, and spinal cord compression, n = 1 each). Two dose-limiting toxicities were experienced at DL4 (thrombocytopenia) and DL5 (transaminitis). Twenty-two patients were evaluable for response; 10 (45%) had stable disease (SD) as the best response. About 8 patients with SD had disease stability of > 4 months. Twelve patients (55%) had progressive disease. The median progression-free survival was 2.4 months (95% CI 1.7-5.3 months). PK data is awaiting final analysis.
The study concluded that metronomic Selinexor was well-tolerated in sarcoma patients, with some signs of clinical benefit. More data is needed to confirm these findings.
Source: https://meetings.asco.org/abstracts-presentations/220628
Clinical Trial: https://clinicaltrials.gov/study/NCT04811196
Aisha Alshibany, Abdulazeez Salawu, Abha A. Gupta, Esmail Mutahar Al-Ezzi, Sofia Genta, Eoghan Ruadh Malone, Geoffrey Alan Watson, Olga Vornicova, Lisa Wang, Limore Arones, Madeline J. Phillips, Jasmine Lee, and Albiruni Ryan Abdul Razak | Journal of Clinical Oncology 2023 41:16_suppl, 11557-11557
