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
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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Maximum tolerated dose and/or Recommended dose of SNS-062 (Phase 1b)
Secondary Outcome
Safety as assessed through reported AEs, SAEs, DLTs and abnormal lab findings (Phase 1b and Phase 2)
Condition
Chronic Lymphocytic Leukemia
Intervention
SNS-062
Study Arms / Comparison Groups
Dose escalating cohorts of SNS-062
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
39
Start Date
April 28, 2017
Completion Date
August 31, 2020
Primary Completion Date
August 31, 2020
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 (Phase 1b). For
Phase 2, CLL/SLL patients with confirmed malignancy with relapsed/refractory disease
after ≥1 line of standard systemic therapy including prior BTK inhibitor 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).
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Gary Acton, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03037645
Organization ID
062-HEM-102
Responsible Party
Sponsor
Study Sponsor
Sunesis Pharmaceuticals
Study Sponsor
Gary Acton, MD, Study Director, Sunesis Pharmaceuticals
Verification Date
October 2020