Safety, PK, PD, and Antitumor Activity of Vecabrutinib (SNS-062) in B Lymphoid Cancers
- Conditions
- Small Lymphocytic LymphomaMantle-Cell LymphomaLymphoplasmacytoid LymphomaWaldenstrom MacroglobulinemiaFollicular LymphomaChronic Lymphocytic LeukemiaDiffuse Large B Cell LymphomaMarginal Zone Lymphoma
- Interventions
- Registration Number
- NCT03037645
- Lead Sponsor
- Sunesis Pharmaceuticals
- Brief Summary
This is an open-label Phase 1b/2 study in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)or non hodgkin's lymphoma (NHL) who have failed prior standard of care therapies including a BTK inhibitor where one is approved for the indication.
- Detailed Description
This study includes 2 parts: phase 1 (dose escalation) and phase 2 (cohort expansion) in patients with CLL/SLL or NHL who have failed prior standard of care therapies including a BTK inhibitor where one is approved for the indication. NHL indications include lymphoplasmacytoid lymphoma/Waldenström's macroglobulinemia (LPL/WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), diffuse large B-cell lymphoma of the activated B-cell subtype (DLBCL-ABC), and follicular lymphoma (FL). In Phase 1b, cohorts of 3 to 6 patients are studied at each dose level, starting with 25 mg vecabrutnib BID in oral capsule form. Following identification of the MTD and/or recommended dose, in Phase 2 only CLL/SLL patients will be enrolled to expansion cohorts to further characterize the clinical activity, safety, and pharmacology of vecabrutinib. Cycle length is 4 weeks.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 39
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose escalating cohorts of SNS-062 SNS-062 Sequential groups, 25, 50, 100, 200, 300, 400 and 500 mg twice daily to determine maximum tolerated dose and recommended dose (RD) in the treatment of various hematological cancers followed by expansion of the recommended dose cohort in Phase 2 of the study treating hematological cancers.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) (Phase 2) Up to approximately 36 months Phase 2 portion of study measuring ORR and corresponding 90% confidence intervals by cohort. ORR will be defined by disease subtype as the proportion of subjects who achieve CLL/SLL: a CR, CRi, or PR.
Maximum tolerated dose and/or Recommended dose of SNS-062 (Phase 1b) Up to approximately 21 months To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD)within the tested SNS-062 dose range. The MTD is the highest tested dose level at which ≥6 subjects have been treated and which is associated with a Cycle 1 dose limiting toxicity (DLT) in \<33% of the subjects. The RD may be the MTD or may be a lower dose.
- Secondary Outcome Measures
Name Time Method Safety as assessed through reported AEs, SAEs, DLTs and abnormal lab findings (Phase 1b and Phase 2) Up to approximately 36 months Type, severity, timing of onset, duration, and relationship to study drug of any TEAEs or abnormalities of laboratory tests, SAEs, DLTs, or AEs leading to study discontinuation.
Characterization of Pharmacokinetics (Cmax) (Phase 1b and Phase 2) Up to approximately 36 months Maximum Plasma Concentration (Cmax)
Preliminary evidence of anti-tumor activity, in terms of Progression-Free Survival (PFS) as assessed by the Investigator. (Phase 2) Up to approximately 36 months Measure of Progression-Free Survival (PFS) as evaluated by standard response and progression criteria for CLL/SLL.
Characterization of Pharmacokinetics (Cmin,ss) (Phase 1b and Phase 2) Up to approximately 36 months Minimum Plasma Concentration During Dosing Interval at Steady-State (Cmin,ss)
Characterization of Pharmacokinetics (Tmax) (Phase 1b and Phase 2) Up to approximately 36 months Time of Maximum Plasma Concentration (Tmax)
Preliminary evidence of anti-tumor activity, in terms of Time to Response (TTR) as assessed by the Investigator. (Phase 2) Up to approximately 36 months Measure of Time to Response (TTR) as evaluated by standard response and progression criteria for CLL/SLL.
Preliminary evidence of anti-tumor activity, in terms of Disease Control Rate (DCR) as assessed by the Investigator. (Phase 2) Up to approximately 36 months Measure of Disease Control Rate (DCR) as evaluated by standard response and progression criteria for CLL/SLL.
Preliminary evidence of anti-tumor activity, in terms of Overall Survival (OS) as assessed by the Investigator. (Phase 2) Up to approximately 36 months Measure of Overall Survival (OS) as evaluated by standard response and progression criteria for CLL/SLL.
Characterization of Pharmacokinetics (AUC) (Phase 1b and Phase 2) Up to approximately 36 months Area Under the Curve (AUC)
Preliminary evidence of anti-tumor activity, in terms of Duration of Response (DOR) as assessed by the Investigator. (Phase 2) Up to approximately 36 months Measure of Duration of Response (DOR) as evaluated by standard response and progression criteria for CLL/SLL.
Preliminary evidence of anti-tumor activity, in terms of Response Rate (RR) as assessed by the Investigator. (Phase 2) Up to approximately 36 months Measure of Response Rate (RR) as evaluated by standard response and progression criteria for CLL/SLL.
Trial Locations
- Locations (11)
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
University of California Irvine Medical Center
🇺🇸Orange, California, United States
UC San Diego Moores Cancer Center
🇺🇸San Diego, California, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Weill Cornell Medicine
🇺🇸New York, New York, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Willamette Valley Cancer Institute and Research Center
🇺🇸Eugene, Oregon, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States