A Study of Selinexor in Combination With Standard of Care Therapy for Newly Diagnosed or Recurrent Glioblastoma

Official Title

A Phase 1/2 Study of Selinexor in Combination With Standard of Care (SoC) Therapy for Newly Diagnosed or Recurrent Glioblastoma

Summary:

This is a Phase 1/2 study of selinexor in combination with standard of care (SoC) therapy for newly diagnosed glioblastoma (nGBM) or recurrent glioblastoma (rGBM). This study will be conducted in 2 phases: a Phase 1a dose finding study followed by Phase 1b (dose expansion) and a Phase 2 randomized efficacy exploration study and will independently evaluate 3 different combination regimens in 3 treatment arms in patients with nGBM (Arms A and B) or with rGBM (Arm C). - Arm A: evaluating the combination of selinexor with radiation therapy (S-RT) in nGBM participants with uMGMT - Arm B: evaluating the combination of selinexor with radiation therapy and temozolomide (TMZ) (S-TRT) in nGBM participants with methylated-O6-methylguanine-DNA-methyltransferase (mMGMT) - Arm C: evaluating the combination of selinexor with lomustine (or carmustine, if lomustine is not available) (S-L/C) in rGBM participants regardless of MGMT status - Arm D: evaluating the combination of selinexor with bevacizumab in rGBM participants regardless of MGMT status - Arm E: evaluating the combination of selinexor with tumour treating fields (TTField) in rGBM participants regardless of MGMT status

Trial Description

Primary Outcome:

• Phase 1a: Maximum Tolerated Dose Per Arm: Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
• Phase 1a: Recommended Phase 2 Dose Per Arm
• Phase 1a: Number of Participants with Adverse Events (AEs) with Grade Greater Than or Equal to (>=) 3, Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation
• Phase 1b: Progressive Free Survival at 3 Months for All Arms
• Phase 1b: Overall Survival (OS) for All Arms
• Phase 2: Progression-free Survival (PFS) in Arms A and B
• Phase 2: Overall Survival (OS) for Arm C

• Phase 1a: Overall Survival (OS) for Each Arm
• Phase 1a/1b: Time to Progression (TTP) for Each Arm
• Phase 1a/1b: Progressive Free Survival (PFS) for Each Arm
• Phase 1a/1b: Overall Response Rate (ORR) Based on Modified Response Assessment in Neuro-Oncology (RANO) Criteria in Arm C, D and E
• Phase 1a/1b: Disease Control Rate (DCR) Based on Modified Response Assessment in Neuro-Oncology Criteria in Arm C, D and E
• Phase 1a/1b: Duration of Response (DOR) in Arm C, D and E
• Phase 1a/1b: Maximum Plasma Concentration (Cmax) of Selinexor
• Phase 1a/1b: Area Under the Concentration-time Curve (AUC) of Selinexor
• Phase 1a/1b: Apparent Clearance (CL) of Selinexor
• Phase 1b: Number of Participants with Adverse Events (AEs) with Grade Greater Than or Equal to (>=) 3, Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation
• Phase 1b: Maximum Tolerated Dose
• Phase 1b: Recommended Phase 2 Dose
• Phase 2: Progression Free Survival Per (PFS) as Assessed by Investigator per Modified Response Assessment in Neuro-Oncology Criteria in Arms A and B
• Phase 2: Overall Survival for Participants With Newly Diagnosed Glioblastoma Multiforme in Arms A and B
• Phase 2: Progression Free Survival (PFS) as Assessed by Independent Review Committee (IRC) per Modified Response Assessment in Neuro-Oncology Criteria in Arm C
• Phase 2: Progression Free Survival (PFS) as Assessed by Investigator per Modified Response Assessment in Neuro-Oncology Criteria in Arm C
• Phase 2: Overall Response Rate (ORR) as Assessed by IRC in Arm C
• Phase 2: Overall Response Rate (ORR) as Assessed by Investigator in Arm C
• Phase 2: Disease Control Rate (DCR) as Assessed by IRC in Arm C(TEAEs) by Severity Grade ≥3, Serious Adverse event (SAEs), and AEs Leading to Treatment Discontinuation
• Phase 2: Disease Control Rate (DCR) as Assessed by Investigator in Arm C
• Phase 2: Duration of Response (DOR) as Assessed by IRC in Arm C
• Phase 2: Duration of Response (DOR) as Assessed by Investigator in Arm C
• Phase 2: Progression Free Survival at 6 Months (PFS6) as Assessed by IRC in all Arms
• Phase 2: Progression Free Survival at 6 Months (PFS6) as Assessed by Investigator in all Arms
• Phase 2: Overall Survival Rate at 12 and 24 Months in all Arms
• Phase 2: Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) by Grade >=3, Serious Adverse event (SAEs), and AEs Leading to Treatment Discontinuation

View this trial on ClinicalTrials.gov