Chronic Lymphocytic Leukemia, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Lymphoplasmacytoid Lymphoma, Mantle-Cell Lymphoma, Marginal Zone Lymphoma, Small Lymphocytic Lymphoma, Waldenstrom Macroglobulinemia
Conditions
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
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.
Interventions
DRUGSNS-062
SNS-062 will be orally administered twice daily and available in capsules containing either 25 mg or 100 mg of active ingredient.
Sponsors
Sunesis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| Characterization of Pharmacokinetics (AUC) (Phase 1b and Phase 2) | Up to approximately 36 months | Area Under the Curve (AUC) |
Countries
United States
Outcome results
None listed