Clinical trial NCT03037645: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: Sunesis Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-01-31
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Maximum tolerated dose and/or Recommended dose of SNS-062 (Phase 1b)
timeFrame: Up to approximately 21 months
measure: Objective Response Rate (ORR) (Phase 2)
timeFrame: Up to approximately 36 months
Secondary outcomes:
measure: Safety as assessed through reported AEs, SAEs, DLTs and abnormal lab findings (Phase 1b and Phase 2)
timeFrame: Up to approximately 36 months
measure: Characterization of Pharmacokinetics (AUC) (Phase 1b and Phase 2)
timeFrame: Up to approximately 36 months
measure: Characterization of Pharmacokinetics (Cmin,ss) (Phase 1b and Phase 2)
timeFrame: Up to approximately 36 months
measure: Characterization of Pharmacokinetics (Cmax) (Phase 1b and Phase 2)
timeFrame: Up to approximately 36 months
measure: Characterization of Pharmacokinetics (Tmax) (Phase 1b and Phase 2)
timeFrame: Up to approximately 36 months
measure: Preliminary evidence of anti-tumor activity, in terms of Time to Response (TTR) as assessed by the Investigator. (Phase 2)
timeFrame: Up to approximately 36 months
measure: Preliminary evidence of anti-tumor activity, in terms of Duration of Response (DOR) as assessed by the Investigator. (Phase 2)
timeFrame: Up to approximately 36 months
measure: Preliminary evidence of anti-tumor activity, in terms of Response Rate (RR) as assessed by the Investigator. (Phase 2)
timeFrame: Up to approximately 36 months
measure: Preliminary evidence of anti-tumor activity, in terms of Disease Control Rate (DCR) as assessed by the Investigator. (Phase 2)
timeFrame: Up to approximately 36 months
measure: Preliminary evidence of anti-tumor activity, in terms of Progression-Free Survival (PFS) as assessed by the Investigator. (Phase 2)
timeFrame: Up to approximately 36 months
measure: Preliminary evidence of anti-tumor activity, in terms of Overall Survival (OS) as assessed by the Investigator. (Phase 2)
timeFrame: Up to approximately 36 months
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: San Diego
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center and Research Institute
state: Florida
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Sunesis Pharmaceuticals
name: Gary Acton, MD
role: STUDY_DIRECTOR
References:
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.