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

October 15, 2020 updated by: Sunesis Pharmaceuticals

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

39

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Orange, California, United States, 92868-3201
        • University of California Irvine Medical Center
      • San Diego, California, United States, 92093
        • UC San Diego Moores Cancer Center
    • Florida
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center and Research Institute
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
    • New York
      • New York, New York, United States, 10065
        • Weill Cornell Medicine
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Willamette Valley Cancer Institute and Research Center
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
      • Tyler, Texas, United States, 75702
        • Texas Oncology - Tyler
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center
      • Seattle, Washington, United States, 98104
        • Swedish Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: SNS-062
SNS-062 will be orally administered twice daily and available in capsules containing either 25 mg or 100 mg of active ingredient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose and/or Recommended dose of SNS-062 (Phase 1b)
Time Frame: 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.
Up to approximately 21 months
Objective Response Rate (ORR) (Phase 2)
Time Frame: 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.
Up to approximately 36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety as assessed through reported AEs, SAEs, DLTs and abnormal lab findings (Phase 1b and Phase 2)
Time Frame: 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.
Up to approximately 36 months
Characterization of Pharmacokinetics (AUC) (Phase 1b and Phase 2)
Time Frame: Up to approximately 36 months
Area Under the Curve (AUC)
Up to approximately 36 months
Characterization of Pharmacokinetics (Cmin,ss) (Phase 1b and Phase 2)
Time Frame: Up to approximately 36 months
Minimum Plasma Concentration During Dosing Interval at Steady-State (Cmin,ss)
Up to approximately 36 months
Characterization of Pharmacokinetics (Cmax) (Phase 1b and Phase 2)
Time Frame: Up to approximately 36 months
Maximum Plasma Concentration (Cmax)
Up to approximately 36 months
Characterization of Pharmacokinetics (Tmax) (Phase 1b and Phase 2)
Time Frame: Up to approximately 36 months
Time of Maximum Plasma Concentration (Tmax)
Up to approximately 36 months
Preliminary evidence of anti-tumor activity, in terms of Time to Response (TTR) as assessed by the Investigator. (Phase 2)
Time Frame: Up to approximately 36 months
Measure of Time to Response (TTR) as evaluated by standard response and progression criteria for CLL/SLL.
Up to approximately 36 months
Preliminary evidence of anti-tumor activity, in terms of Duration of Response (DOR) as assessed by the Investigator. (Phase 2)
Time Frame: Up to approximately 36 months
Measure of Duration of Response (DOR) as evaluated by standard response and progression criteria for CLL/SLL.
Up to approximately 36 months
Preliminary evidence of anti-tumor activity, in terms of Response Rate (RR) as assessed by the Investigator. (Phase 2)
Time Frame: Up to approximately 36 months
Measure of Response Rate (RR) as evaluated by standard response and progression criteria for CLL/SLL.
Up to approximately 36 months
Preliminary evidence of anti-tumor activity, in terms of Disease Control Rate (DCR) as assessed by the Investigator. (Phase 2)
Time Frame: Up to approximately 36 months
Measure of Disease Control Rate (DCR) as evaluated by standard response and progression criteria for CLL/SLL.
Up to approximately 36 months
Preliminary evidence of anti-tumor activity, in terms of Progression-Free Survival (PFS) as assessed by the Investigator. (Phase 2)
Time Frame: Up to approximately 36 months
Measure of Progression-Free Survival (PFS) as evaluated by standard response and progression criteria for CLL/SLL.
Up to approximately 36 months
Preliminary evidence of anti-tumor activity, in terms of Overall Survival (OS) as assessed by the Investigator. (Phase 2)
Time Frame: Up to approximately 36 months
Measure of Overall Survival (OS) as evaluated by standard response and progression criteria for CLL/SLL.
Up to approximately 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sunesis Pharmaceuticals

Investigators

  • Study Director: Gary Acton, MD, Sunesis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 28, 2017

Primary Completion (Actual)

August 31, 2020

Study Completion (Actual)

August 31, 2020

Study Registration Dates

First Submitted

January 25, 2017

First Submitted That Met QC Criteria

January 30, 2017

First Posted (Estimate)

January 31, 2017

Study Record Updates

Last Update Posted (Actual)

October 19, 2020

Last Update Submitted That Met QC Criteria

October 15, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 062-HEM-102

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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