BOSTON: Open-label Study of SVD versus VD in patients with RRMM
Research type
Research Study
Full title
A phase 3 randomized, controlled, open-label study of selinexor, bortezomib, and dexamethasone (SVD) versus bortezomib and dexamethasone (VD) in patients with Relapsed or Refractory Multiple Myeloma (RRMM)
IRAS ID
220722
Contact name
Holger Auner
Contact email
Eudract number
2016-003957-14
Duration of Study in the UK
3 years, 1 months, 1 days
Research summary
Summary of Research
This is a Phase 3 study to compare the efficacy and health-related quality of life and assess the safety of selinexor plus bortezomib plus low-dose dexamethasone (SVd) versus bortezomib plus low-dose dexamethasone (Vd) in adult patients with relapsed or refractory multiple myeloma (RRMM) who have received 1 to 3 prior anti-multiple myeloma (MM) regimens. After progressive disease (PD), patients in the Vd Arm may cross over to SVd treatment (SVdX).This study is based on preliminary supportive data from patients with relapsed MM treated with SVd in Study KCP-330-017 demonstrating that SVd has very high levels of anti-myeloma activity, even in patients with proteasome-inhibitor (PI)-refractory disease, with relatively low adverse event (AE) rates.
Crossover of patients on the control arm (Vd Arm) to SVdX will allow for direct assessment of Selinexor’s ability to restore sensitivity in PI-resistant MM.Approximately 364 patients will be randomised. This study will enrol patients ≥ 18 years of age with RRMM. Patients will be recruited from approximately 120 sites globally.
The length of time that the patients receive study treatment will depend on how well they tolerate their study treatment and the effect it has on their cancer or the progression of their disease. There is no maximum treatment limit in the Selinexor, Bortezomib, and Dexamethasone (SVd) or Bortezomib, and Dexamethasone (Vd) treatment groups for this study. After discontinuation of SVd, Vd, or SVdX, patients will be followed for survival every 3 months until the end of study i.e., when the last patient treated in the study has been followed for up to 5 years after their last dose of SVd/Vd/SVdX treatment.
The study is being funded by Karyopharm Therapeutics Inc.
Summary of Results
Analysis of all safety data from the updated data cut of 15 Jun 2022 was consistent with the data from the original data cut of 15 Feb 2021 and no new or unexpected AEs were observed. In the context of conferring significantly longer PFS and higher ORR, the combination of once-weekly SVd demonstrated no new safety signals but was associated with an increased incidence of delayed onset cataracts (the majority of which occurred >7 months after initiation of therapy). SVd was also associated with similar levels of on-study mortality and demonstrated ~30% less all-grade PN and ~50% less Grade 3/4 PN as compared with standard Vd and required 37% fewer clinic visits with patients receiving 40% less bortezomib in the SVd arm. In addition, once-weekly SVd demonstrated a favorable trend in OS compared to treatment with standard twice-weekly Vd. The results of this study demonstrate a positive benefit-risk profile for patients and warrant the regulatory approval of selinexor in combination with bortezomib and dexamethasone for the treatment of adult patients with MM who have received at least 1 prior therapy.REC name
East of England - Cambridge South Research Ethics Committee
REC reference
17/EE/0177
Date of REC Opinion
14 Jun 2017
REC opinion
Further Information Favourable Opinion