Phase 1
Completed N=33
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
Source: ClinicalTrials.gov NCT02392611 ↗Enrolled (actual)
33
Serious AEs
25.8%
Results posted
Dec 2020
Primary outcomePrimary: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) — 0; 0; 0; 1 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Experiencing Dose Limiting Toxicities (DLTs) |
0; 0; 0; 1; 1; 2 | — |
| SECONDARY Pharmacokinetic (PK) Parameter: Cmax of Alobresib |
35.2; 59.1; 141.0; 197.5; 281.7; 376.2 | — |
| SECONDARY PK Parameter: Ctau of Alobresib |
14.7; 60.7; 34.4; 131.0; 168.4; 237.1 | — |
| SECONDARY PK Parameter: AUC0-24 of Alobresib |
699.5; 1896.1; 1413.2; 2336.1; 2692.1; 6347.4 | — |
| SECONDARY PK Parameter: AUCtau of Alobresib |
643.3; 1838.5; 1591.8; 4391.7; 4128.5; 9373.8 | — |
| SECONDARY PK Parameter: Tmax of Alobresib |
2.1; 4.0; 0.5; 2.0; 0.5; 4.1 | — |
| SECONDARY PK Parameter: t1/2 of Alobresib |
16.6; 35.3; 15.8; 20.2; 19.2; 21.1 | — |
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.
Data sourced from ClinicalTrials.gov (NCT02392611). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.