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

Sponsor

Sunesis Pharmaceuticals (Industry)

Overall Status

Terminated

CT.gov ID

NCT03037645

Collaborator

(none)

Enrollment

Locations

Arm

40.1

Actual Duration (Months)

3.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Lymphoplasmacytoid Lymphoma Mantle-Cell Lymphoma Waldenstrom Macroglobulinemia Diffuse Large B Cell Lymphoma Follicular Lymphoma Marginal Zone Lymphoma	Drug: SNS-062	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

39 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 28, 2017

Actual Primary Completion Date :

Aug 31, 2020

Actual Study Completion Date :

Aug 31, 2020

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose and/or Recommended dose of SNS-062 (Phase 1b) [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.
Objective Response Rate (ORR) (Phase 2) [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.

Secondary Outcome Measures

Safety as assessed through reported AEs, SAEs, DLTs and abnormal lab findings (Phase 1b and Phase 2) [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.
Characterization of Pharmacokinetics (AUC) (Phase 1b and Phase 2) [Up to approximately 36 months]
Area Under the Curve (AUC)
Characterization of Pharmacokinetics (Cmin,ss) (Phase 1b and Phase 2) [Up to approximately 36 months]
Minimum Plasma Concentration During Dosing Interval at Steady-State (Cmin,ss)
Characterization of Pharmacokinetics (Cmax) (Phase 1b and Phase 2) [Up to approximately 36 months]
Maximum Plasma Concentration (Cmax)
Characterization of Pharmacokinetics (Tmax) (Phase 1b and Phase 2) [Up to approximately 36 months]
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) [Up to approximately 36 months]
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) [Up to approximately 36 months]
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) [Up to approximately 36 months]
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) [Up to approximately 36 months]
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) [Up to approximately 36 months]
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) [Up to approximately 36 months]
Measure of Overall Survival (OS) as evaluated by standard response and progression criteria for CLL/SLL.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Irvine Medical Center	Orange	California	United States	92868-3201
2	UC San Diego Moores Cancer Center	San Diego	California	United States	92093
3	Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
4	The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231
5	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
6	Weill Cornell Medicine	New York	New York	United States	10065
7	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon	United States	97401
8	MD Anderson Cancer Center	Houston	Texas	United States	77030
9	Texas Oncology - Tyler	Tyler	Texas	United States	75702
10	Swedish Cancer Institute	Seattle	Washington	United States	98104
11	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109