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

NCT ID: NCT03037645

Last Updated: 2020-10-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-28
• Study Completion Date: 2020-08-31

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose escalating cohorts of 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.

Group Type: EXPERIMENTAL

SNS-062

Intervention Type: DRUG

SNS-062 will be orally administered twice daily and available in capsules containing either 25 mg or 100 mg of active ingredient.

Interventions

SNS-062

SNS-062 will be orally administered twice daily and available in capsules containing either 25 mg or 100 mg of active ingredient.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sunesis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gary Acton, MD

Role: STUDY_DIRECTOR

Sunesis Pharmaceuticals

Locations

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

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Countries

United States

References

Kipps TJ. Mining the Microenvironment for Therapeutic Targets in Chronic Lymphocytic Leukemia. Cancer J. 2021 Jul-Aug 01;27(4):306-313. doi: 10.1097/PPO.0000000000000536.

Reference Type: DERIVED

PMID: 34398557 (View on PubMed)

Other Identifiers

062-HEM-102

Identifier Type: -

Identifier Source: org_study_id