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

Primary Purpose

Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Lymphoplasmacytoid Lymphoma

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

SNS-062

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

University of California Irvine Medical Center
UC San Diego Moores Cancer Center
Moffitt Cancer Center and Research Institute
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Dana-Farber Cancer Institute
Weill Cornell Medicine
Willamette Valley Cancer Institute and Research Center
MD Anderson Cancer Center
Texas Oncology - Tyler
Swedish Cancer Institute
Fred Hutchinson Cancer Research Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dose escalating cohorts of SNS-062

Arm 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.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Safety as assessed through reported AEs, SAEs, DLTs and abnormal lab findings (Phase 1b and Phase 2)

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.

Characterization of Pharmacokinetics (AUC) (Phase 1b and Phase 2)

Area Under the Curve (AUC)

Characterization of Pharmacokinetics (Cmin,ss) (Phase 1b and Phase 2)

Minimum Plasma Concentration During Dosing Interval at Steady-State (Cmin,ss)

Characterization of Pharmacokinetics (Cmax) (Phase 1b and Phase 2)

Maximum Plasma Concentration (Cmax)

Characterization of Pharmacokinetics (Tmax) (Phase 1b and Phase 2)

Time of Maximum Plasma Concentration (Tmax)

Preliminary evidence of anti-tumor activity, in terms of Time to Response (TTR) as assessed by the Investigator. (Phase 2)

Measure of Time to Response (TTR) as evaluated by standard response and progression criteria for CLL/SLL.

Preliminary evidence of anti-tumor activity, in terms of Duration of Response (DOR) as assessed by the Investigator. (Phase 2)

Measure of Duration of Response (DOR) as evaluated by standard response and progression criteria for CLL/SLL.

Preliminary evidence of anti-tumor activity, in terms of Response Rate (RR) as assessed by the Investigator. (Phase 2)

Measure of Response Rate (RR) as evaluated by standard response and progression criteria for CLL/SLL.

Preliminary evidence of anti-tumor activity, in terms of Disease Control Rate (DCR) as assessed by the Investigator. (Phase 2)

Measure of Disease Control Rate (DCR) as evaluated by standard response and progression criteria for CLL/SLL.

Preliminary evidence of anti-tumor activity, in terms of Progression-Free Survival (PFS) as assessed by the Investigator. (Phase 2)

Measure of Progression-Free Survival (PFS) as evaluated by standard response and progression criteria for CLL/SLL.

Preliminary evidence of anti-tumor activity, in terms of Overall Survival (OS) as assessed by the Investigator. (Phase 2)

Measure of Overall Survival (OS) as evaluated by standard response and progression criteria for CLL/SLL.

Full Information

NCT ID

NCT03037645

First Posted

January 25, 2017

Last Updated

October 15, 2020

Sponsor

Sunesis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03037645

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Terminated

Why Stopped

Phase 1b portion completed. Sponsor decided not to proceed with P2 portion of study. Vecabrutinib was very well tolerated, there was insufficient evidence of activity at the doses tested in the Phase 1b to advance to Phase 2.

Study Start Date

April 28, 2017 (Actual)

Primary Completion Date

August 31, 2020 (Actual)

Study Completion Date

August 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sunesis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

39 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose escalating cohorts of SNS-062

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

SNS-062

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Up to approximately 21 months

Title

Objective Response Rate (ORR) (Phase 2)

Description

Time Frame

Up to approximately 36 months

Secondary Outcome Measure Information:

Title

Safety as assessed through reported AEs, SAEs, DLTs and abnormal lab findings (Phase 1b and Phase 2)

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.

Time Frame

Up to approximately 36 months

Title

Characterization of Pharmacokinetics (AUC) (Phase 1b and Phase 2)

Description

Area Under the Curve (AUC)

Time Frame

Up to approximately 36 months

Title

Characterization of Pharmacokinetics (Cmin,ss) (Phase 1b and Phase 2)

Description

Minimum Plasma Concentration During Dosing Interval at Steady-State (Cmin,ss)

Time Frame

Up to approximately 36 months

Title

Characterization of Pharmacokinetics (Cmax) (Phase 1b and Phase 2)

Description

Maximum Plasma Concentration (Cmax)

Time Frame

Up to approximately 36 months

Title

Characterization of Pharmacokinetics (Tmax) (Phase 1b and Phase 2)

Description

Time of Maximum Plasma Concentration (Tmax)

Time Frame

Up to approximately 36 months

Title

Preliminary evidence of anti-tumor activity, in terms of Time to Response (TTR) as assessed by the Investigator. (Phase 2)

Description

Measure of Time to Response (TTR) as evaluated by standard response and progression criteria for CLL/SLL.

Time Frame

Up to approximately 36 months

Title

Preliminary evidence of anti-tumor activity, in terms of Duration of Response (DOR) as assessed by the Investigator. (Phase 2)

Description

Measure of Duration of Response (DOR) as evaluated by standard response and progression criteria for CLL/SLL.

Time Frame

Up to approximately 36 months

Title

Preliminary evidence of anti-tumor activity, in terms of Response Rate (RR) as assessed by the Investigator. (Phase 2)

Description

Measure of Response Rate (RR) as evaluated by standard response and progression criteria for CLL/SLL.

Time Frame

Up to approximately 36 months

Title

Preliminary evidence of anti-tumor activity, in terms of Disease Control Rate (DCR) as assessed by the Investigator. (Phase 2)

Description

Measure of Disease Control Rate (DCR) as evaluated by standard response and progression criteria for CLL/SLL.

Time Frame

Up to approximately 36 months

Title

Preliminary evidence of anti-tumor activity, in terms of Progression-Free Survival (PFS) as assessed by the Investigator. (Phase 2)

Description

Measure of Progression-Free Survival (PFS) as evaluated by standard response and progression criteria for CLL/SLL.

Time Frame

Up to approximately 36 months

Title

Preliminary evidence of anti-tumor activity, in terms of Overall Survival (OS) as assessed by the Investigator. (Phase 2)

Description

Measure of Overall Survival (OS) as evaluated by standard response and progression criteria for CLL/SLL.

Time Frame

Up to approximately 36 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gary Acton, MD

Organizational Affiliation

Sunesis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

University of California Irvine Medical Center

City

Orange

State/Province

California

ZIP/Postal Code

92868-3201

Country

United States

Facility Name

UC San Diego Moores Cancer Center

City

San Diego

State/Province

California

ZIP/Postal Code

92093

Country

United States

Facility Name

Moffitt Cancer Center and Research Institute

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

Facility Name

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21231

Country

United States

Facility Name

Dana-Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

Weill Cornell Medicine

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Willamette Valley Cancer Institute and Research Center

City

Eugene

State/Province

Oregon

ZIP/Postal Code

97401

Country

United States

Facility Name

MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Texas Oncology - Tyler

City

Tyler

State/Province

Texas

ZIP/Postal Code

75702

Country

United States

Facility Name

Swedish Cancer Institute

City

Seattle

State/Province

Washington

ZIP/Postal Code

98104

Country

United States

Facility Name

Fred Hutchinson Cancer Research Center

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34398557

Citation

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.

Results Reference

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

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