safety, pk, pd, and antitumor activity of vecabrutinib (sns-062) in b lymphoid cancers

Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Lymphoplasmacytoid Lymphoma; Mantle-Cell Lymphoma; Waldenstrom Macroglobulinemia; Diffuse Large B Cell Lymphoma; Follicular Lymphoma; Marginal Zone Lymphoma

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.

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).

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