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

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ClinicalTrials.gov Identifier: NCT03037645
Recruitment Status : Recruiting
First Posted : January 31, 2017
Last Update Posted : February 19, 2018
Sponsor:
Information provided by (Responsible Party):
Sunesis Pharmaceuticals

Brief Summary:
Phase 1b (Dose Escalation) in primarily CLL/SLL patients will evaluate safety and pharmacology of self-administered twice a day oral doses beginning at 25 mg/dose for 4 weeks with succeeding cohorts at escalating doses until establishing dose limiting toxicity or, recommended Phase 2 dose. Patient data will be assessed before authorizing dose escalation cohorts. Phase 2 (Cohort Expansion) will follow in cohorts using the recommended dose to explore clinical activity, safety, pharmacology of SNS-062 (vecabrutinib) as monotherapy.

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 Drug: SNS-062 Phase 1 Phase 2

Detailed Description:

Phase 1b (Dose Escalation) This portion of the study will evaluate the safety and pharmacology of a range of SNS-062 (vecabrutinib) dose levels administered to subjects with previously treated B-lymphoid malignancies, including: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lymphoplasmacytoid lymphoma/Waldenström's macroglobulinemia (LPL/WM), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma of the activated B-cell subtype (DLBCL-ABC), and follicular lymphoma (FL).

All subjects will self-administer SNS-062 orally BID. The dose-limiting toxicity (DLT) window will be 4 weeks (1 cycle in length). Assessments on study will be performed in 4-week cycles. Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher dose levels of SNS-062 using a standard 3+3 dose-escalation design.

Based on the pattern of dose-limiting toxicities (DLTs) observed in the first cycle (4 weeks), escalation will proceed to define a maximum tolerated dose (MTD) and/or a recommended dose (RD) that may be the MTD or a lower dose. An additional 6 subjects may be accrued at the MTD or the RD to confirm SNS-062 safety and pharmacology as a prelude to further clinical evaluation. Assessments regarding DLTs and dose escalation will be performed by a Safety Review Committee (SRC) comprising, but not limited to, the principal investigators, the medical monitor and the study sponsor drug safety representative.

Phase 2 (Cohort Expansion) This portion of the study provides cohort expansion to further explore the clinical activity, safety, and pharmacology of SNS-062 monotherapy. Accrual will occur independently for each of the 4 disease and mutation-specific cohorts. Subjects will self-administer SNS-062 orally at the RD of SNS-062 identified in the Phase 1b portion of the study. The SRC will meet regularly to assess the efficacy and safety for each cohort.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 124 participants
Intervention Model: Sequential Assignment
Intervention Model Description: Phase 1b will evaluate the safety and pharmacology of a range of SNS-062 dose levels administered to the subjects. Based on the pattern of dose limiting toxicities observed in the first cycle (4 weeks), escalation will proceed to define a maximum tolerated dose (MTD) and/or a recommended dose (RD). The Phase 2 portion of the study provides cohort expansion to further explore the clinical activity, safety and pharmacology of SNS-062 monotherapy.
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 : April 28, 2017
Estimated Primary Completion Date : September 30, 2018
Estimated Study Completion Date : June 30, 2021


Arm Intervention/treatment
Experimental: Dose escalating cohorts of SNS-062
Sequential groups, 25, 50, 100, 200, 300, 400 and 500 mg twice daily on 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.



Primary Outcome Measures :
  1. 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.

  2. Objective Response Rate (ORR) (Phase 2) [ Time Frame: Approximately 24 months ]

    Phase 2 portion of study measuring ORR and corresponding 95% 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.

    MCL: a CR or PR. LPL/WM: a CR, VGPR, PR, or MR.



Secondary Outcome Measures :
  1. Safety as assessed through reported AEs, SAEs, DLTs and abnormal lab findings [ Time Frame: Up to approximately 24 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.

  2. Characterization of Pharmacokinetics (AUC) [ Time Frame: Up to approximately 24 months ]
    Area Under the Curve (AUC)

  3. Characterization of Pharmacokinetics (Cmax) [ Time Frame: Up to approximately 24 months ]
    Maximum Plasma Concentration (Cmax)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 or MCL and for DLBCL-ABC and FL, after ≥2 lines of standard systemic therapy.
  • Presence of measurable disease through various assessments depending on specific cancer type.
  • Current medical need for therapy of the B-lymphoid malignancy due to disease-related symptoms, lymphadenopathy, organomegaly, extranodal organ involvement, or PD.

Exclusion Criteria (Key factors listed):

  • Known central nervous system malignancy.
  • History of other malignancies except for some which have been adequately treated (e.g., local cancers of the skin, cervix or breast cancers, non-invasive bladder cancer, prostate or other cancers of stages 1 or 2 in complete remission).
  • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03037645


Contacts
Contact: Malathi Robaina 650-266-3766 clinicaltrials@sunesis.com

Locations
United States, California
University of California Irvine Medical Center Recruiting
Orange, California, United States, 92868-3201
Contact: General Contact    877-827-8839    ucstudy@uci.edu   
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Mike Rocchio    617-632-5221    MichaelJ_Rocchio@dfci.harvard.edu   
United States, New York
Weill Cornell Medicine Recruiting
New York, New York, United States, 10065
Contact: Amelyn Rodriguez       amr2017@med.cornell.edu   
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Carol Bivens    713-794-4460    cbibens@mdanderson.org   
United States, Washington
Swedish Cancer Institute Recruiting
Seattle, Washington, United States, 98104
Contact: Ngan Trinh    206-215-2363    Ngan.Trinh@Swedish.org   
Sponsors and Collaborators
Sunesis Pharmaceuticals
Investigators
Study Director: Renee Ward, MD, PhD Sunesis Pharmaceuticals

Responsible Party: Sunesis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03037645     History of Changes
Other Study ID Numbers: 062-HEM-102
First Posted: January 31, 2017    Key Record Dates
Last Update Posted: February 19, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sunesis Pharmaceuticals:
SNS-062
CLL
hematological diseases
relapsed
cancer
malignancy
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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia
Leukemia, B-Cell
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders