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

Chronic Lymphocytic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03037645
• Other study ID #: 062-HEM-102
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: April 28, 2017
• Est. completion date: August 31, 2020

Study information

• Verified date: October 2020
• Source: Sunesis Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 39
• Est. completion date: August 31, 2020
• Est. primary completion date: August 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

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

Intervention

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.

Locations

Country	Name	City	State
United States	The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	MD Anderson Cancer Center	Houston	Texas
United States	Weill Cornell Medicine	New York	New York
United States	University of California Irvine Medical Center	Orange	California
United States	UC San Diego Moores Cancer Center	San Diego	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Swedish Cancer Institute	Seattle	Washington
United States	Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Texas Oncology - Tyler	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Sunesis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to approximately 21 months
Primary	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.	Up to approximately 36 months
Secondary	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.	Up to approximately 36 months
Secondary	Characterization of Pharmacokinetics (AUC) (Phase 1b and Phase 2)	Area Under the Curve (AUC)	Up to approximately 36 months
Secondary	Characterization of Pharmacokinetics (Cmin,ss) (Phase 1b and Phase 2)	Minimum Plasma Concentration During Dosing Interval at Steady-State (Cmin,ss)	Up to approximately 36 months
Secondary	Characterization of Pharmacokinetics (Cmax) (Phase 1b and Phase 2)	Maximum Plasma Concentration (Cmax)	Up to approximately 36 months
Secondary	Characterization of Pharmacokinetics (Tmax) (Phase 1b and Phase 2)	Time of Maximum Plasma Concentration (Tmax)	Up to approximately 36 months
Secondary	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.	Up to approximately 36 months
Secondary	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.	Up to approximately 36 months
Secondary	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.	Up to approximately 36 months
Secondary	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.	Up to approximately 36 months
Secondary	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.	Up to approximately 36 months
Secondary	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.	Up to approximately 36 months