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

Phase 2TerminatedNCT03037645

Sunesis Pharmaceuticals39 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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).

Locations (11)

University of California Irvine Medical Center

Orange, California, United States

UC San Diego Moores Cancer Center

San Diego, California, United States

Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Weill Cornell Medicine

New York, New York, United States

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, United States

MD Anderson Cancer Center

Houston, Texas, United States

Texas Oncology - Tyler

Tyler, Texas, United States

Swedish Cancer Institute

Seattle, Washington, United States

...and 1 more locations

Outcomes

Primary Outcomes

Maximum tolerated dose and/or Recommended dose of SNS-062 (Phase 1b)

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.

Time frame: Up to approximately 21 months

Objective Response Rate (ORR) (Phase 2)

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.