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

Gilead Sciences

Status and phase: Completed; Phase 1

Conditions: Solid Tumors and Lymphomas

Treatments: Drug: Alobresib; Drug: Exemestane; Drug: Fulvestrant

Study type: Interventional

Funder types: Industry

Identifiers

NCT02392611

2016-001912-39 (EudraCT Number)

GS-US-350-1599

Details and patient eligibility

About

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.

Enrollment: 33 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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33 participants in 9 patient groups

Monotherapy: Alobresib 0.6 mg

Experimental group

Description:

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 0.6 mg to determine the MTD.

Treatment:

Drug: Alobresib

Monotherapy: Alobresib 1.4 mg

Experimental group

Description:

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 1.4 mg to determine the MTD.

Treatment:

Drug: Alobresib

Monotherapy: Alobresib 2 mg

Experimental group

Description:

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 2 mg to determine the MTD.

Treatment:

Drug: Alobresib

Monotherapy: Alobresib 3 mg

Experimental group

Description:

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 3 mg to determine the MTD.

Treatment:

Drug: Alobresib

Monotherapy: Alobresib 4 mg

Experimental group

Description:

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 4 mg to determine the MTD.

Treatment:

Drug: Alobresib

Monotherapy: Alobresib 6 mg

Experimental group

Description:

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 6 mg to determine the MTD.

Treatment:

Drug: Alobresib

Combination Therapy: Alobresib 2 mg + Exemestane

Experimental group

Description:

Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy exists, will receive alobresib at a dose of 2 mg in combination with exemestane 25 mg.

Treatment:

Drug: Exemestane

Drug: Alobresib

Combination Therapy: Alobresib 2 mg + Fulvestrant

Experimental group

Description:

Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy exists, will receive alobresib at a dose of 2 mg in combination with fulvestrant 500 mg.

Treatment:

Drug: Fulvestrant

Drug: Alobresib

Combination Therapy: Alobresib 3 mg + Fulvestrant

Experimental group

Description:

Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy exists, will receive alobresib at a dose of 3 mg in combination with fulvestrant 500 mg.

Treatment:

Drug: Fulvestrant

Drug: Alobresib