study to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of alobresib (formerly gs-5829) in adults with advanced solid tumors and lymphomas and in combination with exemestane or fulvestrant in adults with estrogen receptor positive breast cancer

Conditions: Solid Tumors and Lymphomas

Summary: the primary objectives of this study are to characterize the safety and tolerability and determine the maximum tolerated dose (mtd) or recommended dose for phase 2 study (rdp2) of alobresib as a monotherapy in participants with advanced solid tumors and lymphomas, and in combination with exemestane or fulvestrant in participants with advanced estrogen receptor positive breast cancer.


Eligibility criteria:
key inclusion criteria: * group 1: histologically or cytologically confirmed advanced malignant solid tumor or lymphoma (any subtype) that is refractory to or intolerant of standard therapy or for which no standard therapy is available * group 2: post-menopausal women with advanced stage estrogen receptor positive breast cancer who are candidates for exemestane or fulvestrant * group 3: individuals with lymphoma are limited to diffuse large b-cell lymphoma and peripheral t-cell lymphoma that are refractory to or intolerant of standard therapy or for which no standard therapy is available * eastern cooperative oncology group (ecog) performance status of ≤ 1 * adequate organ function defined as follows: * hematologic: platelets ≥ 100 x 10\^9/l; hemoglobin ≥ 9.0 g/ dl; absolute neutrophil count (anc) ≥ 1.5 x 10\^9/l (without platelet transfusion or any growth factors within previous 7 days of the hematologic laboratory values obtained at screening visit). participants in the group 3 lymphoma expansion may be enrolled with an anc of ≥ 1.0 x 10\^9 /l; platelets ≥ 75 x 10\^9 /l. * hepatic: aspartate transaminase (ast) / alanine transaminase (alt) ≤ 2.5 x upper limit of normal (uln) (if liver metastases are present, ≤ 5 x uln); total or conjugated bilirubin ≤ 1.5 x uln * renal: serum creatinine ≤ 1.5 x uln or creatinine clearance (crcl) ≥ 60 ml/min as calculated by the cockcroft-gault method * coagulation: international normalized ratio (inr) ≤ 1.2 key exclusion criteria: * known brain metastasis or leptomeningeal disease * myocardial infarction, symptomatic congestive heart failure (new york heart association classification \> class ii), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of study day 1 * major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (ie, larger than what is required for placement of central venous access, percutaneous feeding tube, or biopsy) within 28 days of first dose of study drug * history of long qt syndrome or whose corrected qt interval (qtc) measured (fridericia method) at screening is prolonged (\> 450 ms for males and \> 470 ms for females). individuals who screen-fail due to this criterion are not eligible to be re-screened * clinically significant bleeding within 28 days of study day 1 * known human immunodeficiency virus (hiv) infection * hepatitis b surface antigen positive * hepatitis c virus (hcv) antibody positive * no active anticoagulation within 7 days of study day 1; including acetylsalicylic acid, low molecular weight heparin, or warfarin. note: other protocol defined inclusion/exclusion criteria may apply.

Keywords: estrogen receptor positive breast cancer