Male or female adult patients with an advanced B-Lymphoid malignancies that have relapsed/progressed after appropriate prior therapy and have resistance and/or mutations that may respond to subsequent BTK inhibition using SNS-062. MedDRA version: 20.0 Level: HLT Classification code 10026798 Term: Mantle cell lymphomas System Organ Class: 100000004851 MedDRA version: 20.1 Level: HLT Classification code 10047802 Term: Waldenstrom's macroglobulinaemias System Organ Class: 100000004851 MedDRA ver
Conditions
Interventions
Product Name: Vecabrutinib
Product Code: SNS-062
Pharmaceutical Form: Capsule
INN or Proposed INN: vecabrutinib
CAS Number: 194740-349-7
Current Sponsor code: SNS-062
Other descriptive name: VECABRUTI
Sponsors
Sunesis Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Men and women of age =18 years 2)Eastern Cooperative Oncology Group (ECOG) Performance Status of =2 3)Histologically confirmed malignancy with relapsed/refractory disease: a)After =2 lines of standard systemic therapy including prior BTK inhibitor therapy: i)CLL ii)LPL/WM iii)MCL b)After =2 lines of standard systemic therapy: i)DLBCL-ABC ii)FL 4)For subjects in: a)Phase 1b and 2: Availability of a peripheral blood sample or a bone marrow aspirate or a lymph node biopsy obtained during the screening period for evaluation of predictive/prognostic disease parameters and to determine if there is a functional BTK C481 mutation (ie BTK C481S) or a resistance or gain of function mutation(s) (ie, PLC?2 R665W) b)Phase 2 only: i)For CLL: the presence of a functional BTK C481 mutation (ie, =1% BTK C481 mutation), and absence of a resistance or gain of function mutation (ie, PLC?2 R665W) or ii)For CLL: absence of a functional BTK C481mutation alone (45 mL/minute (with eClCR to be calculated by the Cockcroft-Gault formula [Appendix 3]), OR b)Measured creatinine clearance >45 mL/minute (assessed with a 24 hour urine collection) 12)Adequate pancreatic profile: a)Serum amylase =1.5 × ULN (Grade =1) b)Serum lipase =1.5 × ULN (Grade =1) 13)Haematology Requirements: a)Platelet count =50 × 109/L (Grade =2) maintained for =7 days after any prior transfusion b)For subjects without bone marrow involvement: i)Absolute neutrophil count (ANC) =0.750 × 109/L ii)Hemoglobin (Hb) =8.0 g/dL, stable for =7 days c)For subjects with bone marrow involvement: i)Absolute neutrophil count (ANC) =500 cells/µL 14)Adequate coagulation
Exclusion criteria
Exclusion criteria: 1)Transformed disease at time of screening (eg, Richter’s transformation or of blastoid variant MCL) 2)Known central nervous system malignancy Note:Central nervous system imaging is only required in subjects with suspected central nervous system malignancy. 3)History of another malignancy except for the following adequately treated: a)Local basal cell or squamous cell carcinoma of the skin b)Carcinoma in situ of the cervix or breast c)Papillary, noninvasive bladder cancer d)Prostate cancer Stage 1 and 2 for which observation is clinically indicated with stable prostate-specific antigen (PSA) for 6 months e)Other Stage 1 or 2 cancers currently in complete remission f)Any other cancer that has been in complete remission for 2 years or surgically cured 4)Significant cardiovascular disease a)Myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism within 6 months prior to start of study therapy b)Symptomatic angina c)Symptomatic peripheral vascular disease d)New York Heart Association Class =3 congestive heart failure e)Uncontrolled Grade =3 hypertension (diastolic blood pressure =100 mmHg or systolic blood pressure =160 mmHg) despite antihypertensive therapy f)Uncontrolled arrhythmia 5)Significant screening ECG abnormalities: a)Left bundle branch block b)2nd or 3rd-degree Atrioventricular block Type 2 c)Grade =2 bradycardia d)QTc by either Bazett or Fridericia method (QTcB or QTcF) >450 msec (for men) or >470 msec (for women) 6)Gastrointestinal disease (eg, gastric or intestinal bypass surgery, pancreatic enzyme insufficiency, malabsorption syndrome, symptomatic inflammatory bowel disease, chronic diarrheal illness, bowel obstruction) that might interfere with drug absorption or with interpretation of gastrointestinal AEs 7)Ongoing risk for bleeding due to any of the following: a)Bleeding diathesis b)Known platelet function disorder c)Uncontrolled peptic ulcer disease d)Oral anticoagulation (eg, warfarin, apixaban, rivaroxaban, dabigatran etexilate) e)Heparin, low-molecular-weight heparin or heparin fractions (eg, enoxaparin, dalteparin, fondaparinux) Note:Use of heparin or thrombolytic agents for local maintenance or clearance of a central venous catheter is permitted. 8)Evidence of an uncontrolled systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) at the time of start of study therapy Note:Subjects with localized fungal infections of skin or nails are eligible. 9)Demonstrated intolerance to a BTK inhibitor as evidenced by discontinuation of BTK inhibitor due to AE or required dose reduction due to AE 10)Transplant a)Evidence of ongoing graft-versus-host disease after prior stem cell transplant b)Prior solid organ transplant 11)Pregnancy or breastfeeding 12)Major surgery within 4 weeks before the start of study therapy 13)Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids except as noted Note:At screening, subjects may be using systemic corticosteroids (at physiologic doses of =10 mg/day of prednisone or equivalent) or topical or inhaled corticosteroids. 14)Use of a moderate or strong inhibitor or inducer of CYP3A4 within 7 days prior to the start of study therapy or expected requirement for use during study therapy 15)Use of substrates of CYP2C8, CYP3A4, CYP2B6, CYP2C9 and CYP2D6 with narrow therapeutic index within 7 days prior to the start of study therapy or expected requirement for
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1b: To determine the MTD and/or RD of SNS-062 Phase 2: To evaluate the objective response rate (ORR) by cohort in subjects receiving SNS-062 ;Secondary Objective: Phase 1b: - To characterize the safety profile of SNS-062 - To characterize the PK profile of SNS-062 - To characterize the antitumor activity of SNS-062 - To assess the preliminary effect of SNS-062 on the QTc interval Phase 2: - To further characterize additional antitumor activity by cohort in subjects receiving SNS-062 - To characterize the safety profile of SNS-062 - To characterize the plasma PK profile of SNS-062 - To assess the preliminary effect of SNS-062 on the QTc interval ;Primary end point(s): Phase 1b: MTD and/or RD within the tested SNS-062 dose range Phase 2: ORR by cohort as evaluated by standard response and progression criteria for each tumor type ;Timepoint(s) of evaluation of this end point: Throughout the trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 1b: - Type, frequency, severity, and relatedness to study drug of treatment emergent adverse events (TEAEs), laboratory abnormalities, or electrocardiogram (ECG) findings - SNS-062 plasma PK parameters (including area under the plasma concentration-time curve [AUC], maximum concentration [Cmax], time of maximum concentration [Tmax], half-life [t1/2], apparent volume of distribution [Vd/F], terminal elimination rate constant [?z], and apparent clearance [Cl/F]) - ORR, time to response (TTR), duration of response (DOR), progression-free-survival (PFS), as evaluated by standard response and progression criteria for each tumor type - QTc interval parameters, including changes from baseline and absolute increases in QTc interval Phase 2b - TTR, DOR, PFS, and OS by cohort as evaluate and progression criteria for each tumor type - Type, frequency, severity, and relatedness to study drug of TEAEs, laboratory abnormalities, or ECG findings - SNS 062 plasma PK parameters (including AUC, Cmax, Tmax, t1/2,Vd/FF, ?z, and Cl/F) - QTc interval parameters, including changes from baseline and absolute increases in QTc interval ;Timepoint(s) of evaluation of this end point: - Type, frequency, severity, and relatedness to study drug of TEAEs, laboratory abnormalities, or ECG findings: thoughout the trial - SNS 062 plasma PK parameters: Cycle 1 days 1,2,8,15, Cycle 2 Day 1 - ORR, TTR, DOR, PFS, and OS : throughout the trial - QTc : Cycle 1 days 1, 2, 8, 15, Cycle 2 Day 1 to Cycle X day 1, EoT | — |
Countries
France, Germany, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
Medpace
Outcome results
None listed