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
Condition: Solid Tumors and Lymphomas
MeSH terms: Lymphoma
Intervention: Alobresib; Exemestane; Fulvestrant
Intervention description: Tablet administered orally once daily on Study Day 1 through Cycle 1 Day 28 of 28 days cycle; Tablets administered orally once daily on Cycle 1 Day 1 of 28 days cycle; Administered intramuscularly on Cycle 1 Day 1 of 28 days cycle and every 28 days
Intervention MeSH terms: Fulvestrant; Exemestane
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Estrogen Receptor Positive Breast Cancer

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.