Phase 2
Completed N=118
Safety and Efficacy Study of Sapanisertib in Combination With Exemestane or Fulvestrant in Postmenopausal Women With Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Metastatic Breast Cancer
Source: ClinicalTrials.gov NCT02049957 ↗Enrolled (actual)
118
Serious AEs
22.0%
Results posted
Jan 2020
Primary outcomePrimary: Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) — 6; 6; 3; 3 Participants
Summary
This is a phase 1b/2 study of the safety and efficacy of sapanisertib (MLN0128) in combination with exemestane or fulvestrant therapy in women with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced or metastatic breast cancer who progressed on treatment with everolimus in combination with exemestane or fulvestrant.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
6; 6; 3; 3; 6; 1 | — |
| PRIMARY Phase 2: Clinical Benefit Rate at 16 Weeks (CBR-16) |
44; 50; 23; 25 | — |
| SECONDARY Phase 2: Clinical Benefit Rate at 24 Weeks (CBR-24) |
28; 38; 23; 25 | — |
| SECONDARY Phase 2: Overall Response Rate (ORR) |
7; 13; 0; 13 | — |
| SECONDARY Phase 2: Progression-Free Survival (PFS) |
4.1; 5.5; 3.3; 5.4 | — |
| SECONDARY Phase 2: Overall Survival (OS) |
15.9; 20.7; 14.0; 13.0 | — |
| SECONDARY Phase 2: Best Percent Change From Baseline in Tumor Size |
-0.46; 0.96; 1.76; -18.91 | — |
| SECONDARY Phase1: Cmax: Maximum Observed Plasma Concentration for Sapanisertib |
57.72; 47.40; 50.90; 45.37; 38.68; 44.96 | — |
| SECONDARY Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Sapanisertib |
3.005; 0.600; 1.035; 2.000; 2.280; 3.500 | — |
| SECONDARY Phase 1: AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for Sapanisertib |
577.081; 178.063; 332.618; 277.626 | — |
| SECONDARY Phase 1: AUC(0-last): Area Under the Plasma Concentration-time Curve From Time 0 to Last Extrapolated Concentration Over the Dosing Interval for Sapanisertib |
577.081; 164.123; 332.618; 251.165; 101.599; 109.496 | — |
| SECONDARY Phase 1: Terminal Elimination Half-life (T1/2) for Sapanisertib |
6.639; 3.161; 7.777; 5.370 | — |
Eligibility Criteria
Inclusion Criteria
Each patient must meet all of the following inclusion criteria to be enrolled in the study:
Phase 1b and Phase 2
- Advanced or metastatic breast cancer.
- Histological or cytological confirmation of ER+ status (defined as > 1% positive tumor cells), and histological or cytological confirmation of HER2-negative (HER2-) status by local laboratory testing using criteria in the American Society of Oncology (ASCO)/College of American Pathologists (CAP) Clinical Practice Guideline update.
- Female patients 18 years of age or older who are postmenopausal for at least 1 year before the Screening visit, where menopause is defined by: Age ≥ 55 years and 1 year or more of amenorrhea. Surgical menopause with bilateral oophorectomy
Age 7%; patients with a history of transient glucose intolerance due to corticosteroid administration may be enrolled in this study if all other inclusion/exclusion criteria are met.
- Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise participation of the patient in the study.
- Known human immunodeficiency virus infection.
- History of any of the following within the last 6 months before administration of the first dose of MLN0128:
- Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures
- Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures
- Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia)
- Placement of a pacemaker for control of rhythm
- New York Heart Association Class III or IV heart failure
- Pulmonary embolism
- Significant active cardiovascular or pulmonary disease before administration of the first dose of MLN0128, including:
- Uncontrolled hypertension (ie, systolic blood pressure > 180 mm Hg; diastolic blood pressure > 95 mm Hg)
- Pulmonary hypertension
- Uncontrolled asthma or oxygen saturation 480 ms, or history of congenital long QT syndrome, or torsades de pointes)
- Diagnosed or treated for another malignancy within 2 years before administration of the first dose of MLN0128 or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
Phase 1b Only: In addition to the previously mentioned exclusion criteria, patients meeting the following exclusion criterion are not to be enrolled in the phase 1b portion of the study:
- More than 3 prior chemotherapy regimens for locally advanced or metastatic disease.
Phase 2 Only: In addition to the previously mentioned exclusion criteria, patients meeting the following exclusion criterion are not to be enrolled in the phase 2 portion of the study:
- More than 1 prior chemotherapy regimen for locally advanced or metastatic disease.
Data sourced from ClinicalTrials.gov (NCT02049957). 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.