Clinical Trials /

Safety, PK, PD, and Antitumor Activity of Vecabrutinib (SNS-062) in B Lymphoid Cancers

NCT03037645

Description:

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.

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma Activated B-Cell Type
  • Follicular Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Waldenstrom Macroglobulinemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety, PK, PD, and Antitumor Activity of Vecabrutinib (SNS-062) in B Lymphoid Cancers
  • Official Title: A Phase 1b/2 Dose-Escalation and Cohort-Expansion Study of the Noncovalent, Reversible Bruton's Tyrosine Kinase Inhibitor, SNS-062, in Patients With B-Lymphoid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 062-HEM-102
  • NCT ID: NCT03037645

Conditions

  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Lymphoplasmacytoid Lymphoma
  • Mantle-Cell Lymphoma
  • Waldenstrom Macroglobulinemia
  • Diffuse Large B Cell Lymphoma
  • Follicular Lymphoma
  • Marginal Zone Lymphoma

Interventions

DrugSynonymsArms
SNS-062Dose escalating cohorts of SNS-062

Purpose

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 patients will be
      enrolled to expansion cohorts to further characterize the clinical activity, safety, and
      pharmacology of vecabrutinib. Cycle length is 4 weeks.
    

Trial Arms

NameTypeDescriptionInterventions
Dose escalating cohorts of SNS-062ExperimentalSequential 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.
  • SNS-062

Eligibility Criteria

        Inclusion Criteria (Key factors listed):

          -  Eastern Cooperative Oncology Group Performance Status of ≤2.

          -  Confirmed malignancy with relapsed/refractory disease after ≥2 lines of standard
             systemic therapy including prior BTK inhibitor therapy having CLL, LPL/WM, MCL or MZL
             and for DLBCL-ABC and FL, after ≥2 lines of standard systemic therapy.

          -  Presence of measurable disease through various assessments depending on specific
             cancer type.

          -  Current medical need for therapy of the B-lymphoid malignancy.

        Exclusion Criteria (Key factors listed):

          -  Active central nervous system involvement.

          -  History of second primary malignancy that has progressed or required systemic
             treatment in the past 2 years. Exceptions include: local cancers of the skin, cervix
             or breast cancers, non-invasive bladder cancer, hormone sensitive prostate cancer with
             stable PSA ≥3 months, and other localized solid tumors in situ/other low risk cancers.

          -  Significant cardiovascular disease or electrocardiogram (ECG) abnormalities

          -  Ongoing risk for bleeding due to bleeding diathesis, platelet function disorder,
             uncontrolled peptic ulcer disease, oral anticoagulation medications.

          -  Evidence of uncontrolled systemic bacterial, fungal or viral infections at the start
             of drug therapy.

          -  Demonstrated intolerance to BTK inhibitor as shown by discontinuation due to adverse
             effects.

          -  Use of a moderate or strong inhibitor or inducer of CYP3A4 within 7 days prior to
             start of study therapy (e.g., some antibiotics, antifungals, anticonvulsants,
             grapefruit).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose and/or Recommended dose of SNS-062 (Phase 1b)
Time Frame:Up to approximately 21 months
Safety Issue:
Description: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

Measure:Safety as assessed through reported AEs, SAEs, DLTs and abnormal lab findings
Time Frame:Up to approximately 24 months
Safety Issue:
Description: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.
Measure:Characterization of Pharmacokinetics (AUC)
Time Frame:Up to approximately 24 months
Safety Issue:
Description:Area Under the Curve (AUC)
Measure:Characterization of Pharmacokinetics (Cmax)
Time Frame:Up to approximately 24 months
Safety Issue:
Description:Maximum Plasma Concentration (Cmax)

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sunesis Pharmaceuticals

Trial Keywords

  • CLL
  • hematological diseases
  • relapsed
  • cancer
  • malignancy
  • SNS-062
  • B-lymphoid
  • chronic lymphocytic leukemia
  • small lymphocytic lymphoma
  • lymphoplasmacytoid lymphoma
  • Waldenström's macrogloulinemia
  • mantle cell lymphoma
  • SLL
  • LPL
  • WM
  • MCL
  • refractory
  • DLBCL-ABC
  • DLBCL
  • follicular lymphoma
  • diffuse large B-cell lymphoma
  • CLL/SLL
  • MZL
  • marginal zone lymphoma

Last Updated

August 12, 2019