CompletedNCT02049957Updated Feb 8, 2023Results posted

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

A Phase 2 interventional study of Sapanisertib and Fulvestrant in Breast Cancer, sponsored by Calithera Biosciences, Inc. Completed at 40 sites in 3 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-02-08.

Sponsored by Calithera Biosciences, Inc · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 118
Allocation: Non-randomized
Ages: 18 Years and older
Sex: Female

Study 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.

Read the detailed description

The drug being tested in this study is called sapanisertib (MLN0128). Sapanisertib is being tested 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. This study will look at the safety and efficacy of sapanisertib when given in combination with exemestane or fulvestrant.

The study enrolled 118 patients. This study has two phases: phase 1 and phase 2. Phase 1 has 2 parts. In part 1 of phase 1, unmilled active pharmaceutical ingredient (API) capsules were administered, while in part 2, capsules based on milled API were administered.

Phase 1 (Part 1): sapanisertib 5 mg (unmilled) + exemestane
Phase 1 (Part 1): sapanisertib 5 mg (unmilled) + fulvestrant
Phase 1 (Part 2): sapanisertib 3 mg (milled) + exemestane
Phase 1 (Part 2): sapanisertib 3 mg (milled) + fulvestrant
Phase 1 (Part 2): sapanisertib 4 mg (milled) + exemestane

In phase 2, participants were enrolled into one of 2 parallel cohorts, depending on the quality and/or duration of their prior response to everolimus in combination with either exemestane (any country) or fulvestrant (US only).

Everolimus-Resistant Cohort: patients who had progressed on treatment with everolimus in combination with either exemestane (any country) or fulvestrant (US only) without achieving an objective response (CR or PR) or after achieving stable disease for \<6 months as their best response.

Everolimus-Sensitive Cohort: participants who had progressed on treatment after achieving a CR or PR of any duration, or stable disease for ≥6 months with prior everolimus treatment in combination with either exemestane (any country) or fulvestrant (US only). Participants were to receive MLN0128 in combination with the same dose of the previously administered treatment (exemestane [any country] or fulvestrant [US only]).

This multi-center trial will be conducted worldwide. The overall time to participate in this study was 52 months. Participants made multiple visits to the clinic and were contacted by telephone every 3 months for a follow-up assessment.

Conditions studied

Breast Cancer

Browse trials for

Breast Neoplasms 12,544

Keywords

Sapanisertib
MLN0128

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 118 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

Calithera Biosciences, Inc is the lead sponsor of 29 studies on the registry; none are open to participants now.

Of its 17 completed or terminated interventional studies of FDA-regulated products, 10 (59%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: Female
Accepts healthy volunteers: No

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 \< 55 years and 1 year or more of amenorrhea, with an estradiol assay \< 20 pg/mL
Note: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression.
Have a history of brain metastasis are eligible for the study provided that all the following criteria are met:
Brain metastases which have been treated
- No evidence of disease progression for ≥ 3 months or hemorrhage after treatment
- Off-treatment with dexamethasone for 4 weeks before administration of the first dose of MLN0128
- No ongoing requirement for dexamethasone or anti-epileptic drugs
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
Clinical laboratory values as specified below within 4 weeks before the first dose of MLN0128:
- Bone marrow reserve consistent with absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L; platelet count ≥ 100 x 10\^9/L; hemoglobin ≥ 9 g/dL
- Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present)
- Creatinine clearance ≥ 50 mL/min based either on Cockcroft-Gault estimate or based on a 12- or 24-hour urine collection
- Fasting serum glucose ≤ 130 mg/dL and fasting triglycerides ≤ 300 mg/dL
Left ventricular ejection fraction (LVEF) within 5 absolute percentage points of institutional standard of normal as measured by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) within 4 weeks before the first dose of MLN0128 (ie, if the institutional standard of normal is 50%, LVEF may be as low as 45% to be eligible for the study).
Able to provide paraffin blocks or a minimum of 10 unstained slides of available archival tumor tissues (paraffin blocks are preferred). If archival tumor tissue is not available, a tumor biopsy may be performed before the patient begins treatment with MLN0128. If fewer than 10 slides are available or the tumor content/area requirements are not met, study eligibility will be determined upon discussion with the sponsor.
Ability to swallow oral medications, willingness to perform mucositis prophylaxis, and suitable venous access for the study-required blood sampling.
Voluntary written consent must be given before the performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
Phase 1b Only: In addition to the previously mentioned inclusion criteria, each patient must meet the following inclusion criterion to be enrolled in the phase 1b portion of the study:
Patients may have SD or disease progression during their most recent treatment with exemestane or fulvestrant, or everolimus in combination with either exemestane (any country) or fulvestrant (US only). Exemestane or fulvestrant in combination with MLN0128 can also be initiated as a new line of therapy.
Phase 2 Only: In addition to the previously mentioned inclusion criteria, each patient must meet all of the following inclusion criteria to be enrolled in the phase 2 portion of the study:
Measurable disease defined as follows:
- At least 1 extra-osseous lesion that can be accurately measured in at least 1 dimension. The lesion must measure ≥ 20 mm with conventional imaging techniques or ≥ 10 mm with spiral computed tomography (CT) or magnetic resonance imaging (MRI), or
- Bone lesions (lytic or mixed [lytic plus sclerotic]) in the absence of measurable disease as defined above
Patients must have had disease progression during treatment with everolimus in combination with either exemestane (any country) or fulvestrant (US only) (duration of treatment ≥ 4 weeks) and must have tolerated everolimus treatment in combination with exemestane (any country) or fulvestrant (US only) adequately according to the treating physician's judgment. Everolimus in combination with exemestane or fulvestrant is not required to be the most recent treatment before enrollment, but progression on the most recent anticancer therapy is required for enrollment.

Exclusion criteria

Exclusion Criteria

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

Phase 1b and Phase 2

Prior anticancer therapy or other investigational therapy within 2 weeks before administration of the first dose of MLN0128 (except for exemestane or fulvestrant, which should be continued). Treatment with everolimus must be discontinued 2 weeks before administration of the first dose of MLN0128.
Chronic concomitant therapy with bisphosphonates or denosumab for the prevention of bone metastases. Concomitant treatment with bisphosphonates or denosumab is permitted for treatment of osteoporosis or management of existing bone metastases if initiated at least 4 weeks before administration of the first dose of MLN0128.
Initiation of treatment with hematopoietic growth factors, transfusions of blood and blood products, or systemic corticosteroids (either IV or oral steroids, excluding inhalers) within 1 week before administration of the first dose of MLN0128 (patients already receiving erythropoietin on a chronic basis for ≥ 4 weeks are eligible).
Previous treatment with dual PI3K/mTOR inhibitors or TORC1/2 inhibitors.
Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of MLN0128.
Poorly controlled diabetes mellitus defined as glycosylated hemoglobin (HbA1c) > 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 \< 90% by arterial blood gas analysis or pulse oximetry on room air
- Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention; or history of valve replacement
- Medically significant (symptomatic) bradycardia
- History of arrhythmia requiring an implantable cardiac defibrillator
- Baseline prolongation of the rate-corrected QT interval (QTc; eg, repeated demonstration of QTc interval > 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.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 118 participants (actual)

Study arms

Experimental
Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane
Sapanisertib 5 mg, unmilled active pharmaceutical ingredient (API) capsule, once daily in a 28-day cycle plus exemestane 25 mg, tablets, once daily in a 28-day cycle (Up to 12 cycles).
Drug: Sapanisertib · Drug: Exemestane
Experimental
Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant
Sapanisertib 5 mg, unmilled API capsule, once daily in a 28-day cycle plus fulvestrant 500 mg, injection, intramuscularly (IM), once on Day 1 of each cycle (Up to 57 cycles).
Drug: Sapanisertib · Drug: Fulvestrant
Experimental
Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane
Sapanisertib 3 mg, milled API capsule, once daily in a 28-day cycle plus exemestane 25 mg, tablets, once daily in a 28-day cycle (Up to 8 cycles).
Drug: Sapanisertib · Drug: Exemestane
Experimental
Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant
Sapanisertib 3 mg, milled API capsule, once daily in a 28-day cycle up to 14 cycles plus fulvestrant 500 mg, injection, IM, once on Day 1 of each cycle (Up to 14 cycles).
Drug: Sapanisertib · Drug: Fulvestrant
Experimental
Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane
Sapanisertib 4 mg, milled API capsule, once daily, in a 28-day cycle plus exemestane 25 mg, tablets, once daily in a 28-day cycle (Up to 18 cycles).
Drug: Sapanisertib · Drug: Exemestane
Experimental
Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)
Sapanisertib 4 mg, milled API capsule once daily in a 28-day cycle plus exemestane 25 mg, tablets, once daily in a 28-day cycle (Up to 14 cycles) in everolimus sensitive participants.
Drug: Sapanisertib · Drug: Exemestane
Experimental
Phase 2:Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)
Sapanisertib 4 mg, milled API capsule once daily in a 28-day cycle plus fulvestrant 500 mg, injection IM, once on Day 1 of each cycle (Up to 17 cycles) in everolimus sensitive participants.
Drug: Sapanisertib · Drug: Fulvestrant
Experimental
Phase 2: Sapanisertib 4 mg+Exemestane (Everolimus Resistant)
Sapanisertib 4 mg, milled API capsule, once daily, in a 28-day cycle plus once daily in a 28-day cycle (Up to 12 cycles) in everolimus resistant participants.
Drug: Sapanisertib · Drug: Exemestane
Experimental
Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)
Sapanisertib 4 mg, milled API capsule, once daily in a 28-day cycle plus fulvestrant 500 mg, injection IM, once on Day 1 of each cycle (Up to 9 cycles) in everolimus resistant participants.
Drug: Sapanisertib · Drug: Fulvestrant

Interventions

DrugSapanisertib
Sapnisertib capsules
Also known as: MLN0128
DrugFulvestrant
Fulvestrant IM injection.
DrugExemestane
Exemestane tablets.

What researchers measure

Primary outcomes

Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug. A SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug will be determined by the Investigator.
Time frame: First dose of study drug through 30 days after the last dose (Up to 52 months)
Phase 2: Clinical Benefit Rate at 16 Weeks (CBR-16)
CBR-16 was defined as the percentage of participants who achieved confirmed complete response (CR) or partial response (PR) of any duration or had confirmed stable disease (SD) as best response and the first 2 or more post baseline scans had PR/SD and the duration of SD was \>112 days. Disease response was assessed for target lesions by computed tomography (CT) or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. CR is disappearance of all target lesions. PR is \>=30% decrease in the sum of the longest diameter of target lesions. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression (PD).
Time frame: Week 16

Secondary outcomes

Phase 2: Clinical Benefit Rate at 24 Weeks (CBR-24)
CBR-24 was defined as the percentage of participants who achieved confirmed CR or PR at any time or had confirmed SD as best response and the first 2 or more post baseline scans had PR/SD and the duration of stable disease was \>168 days. Disease response was assessed for target lesions by CT or MRI according to RECIST version 1.1 guidelines. CR is disappearance of all target lesions. PR is \>=30% decrease in the sum of the longest diameter of target lesions. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: Week 24
Phase 2: Overall Response Rate (ORR)
ORR is defined as the percentage of participants with confirmed CR or PR as per RECIST version1.1 guidelines. CR is disappearance of all target lesions. PR is \>=30% decrease in the sum of the longest diameter of target lesions.
Time frame: Baseline then every 2 cycles from Cycles 2 through 6, and every 3 cycles thereafter in a 28-day cycle up to End of Treatment (EOT) (Up to 24 months)
Phase 2: Progression-Free Survival (PFS)
PFS is defined as the time in months from the date of first dose of study treatment to the date of the first documented disease progression or death. Disease progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; or the appearance of one or more new lesions.
Time frame: Baseline then every 2 cycles from Cycles 2 through 6, and every 3 cycles thereafter in a 28-day cycle, then every 3 months after EOT until disease progression or death (Up to 24 months)
Phase 2: Overall Survival (OS)
OS is the time in months from start of study treatment to date of death due to any cause. Data for the analysis of OS included the censored data at the timepoint that the participant was last known to be alive.
Time frame: Up to 24 months
Phase 2: Best Percent Change From Baseline in Tumor Size
Time frame: Baseline to Month 24
Phase1: Cmax: Maximum Observed Plasma Concentration for Sapanisertib
Time frame: Cycle 1 Day 15 and Cycle 2 Day 1 pre-dose and multiple timepoints (Up to 8 hours) post-dose
Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Sapanisertib
Time frame: Cycle 1 Day 15 and Cycle 2 Day 1 pre-dose and multiple timepoints (Up to 8 hours) post-dose
Phase 1: AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for Sapanisertib
AUC(0-24) is the area under the plasma concentration-time curve of the samples collected up to 8 hours and extrapolated up to 24 hours.
Time frame: Cycle 1 Day 15 pre-dose and multiple timepoints (Up to 8 hours) post-dose, extrapolated to 24 hours post-dose
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
AUC(0-last) is the area under the plasma concentration-time curve of the samples collected up to 8 hours and extrapolated up to last time point.
Time frame: Cycle 1 Day 15 pre-dose and multiple timepoints (Up to 8 hours) post-dose, extrapolated to last timepoint
Phase 1: Terminal Elimination Half-life (T1/2) for Sapanisertib
Time frame: Cycle 1 Day 15 pre-dose and multiple timepoints (Up to 8 hours) post-dose

Results

Posted Jan 27, 2020

Participant flow

Participants took part in the study at 40 investigative sites in Belgium, France and the United States from 13 February 2014 to 03 July 2018.

Participant flow — Overall Study
Milestone	Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)
Started	6	6	3	3	6	43	8	35	8
Completed	0	0	0	0	0	0	0	0	0
Not completed	6	6	3	3	6	43	8	35	8
Withdrew: Progressive disease	5	4	2	2	6	35	7	26	6
Withdrew: Adverse event	1	1	1	0	0	5	0	6	1
Withdrew: Study terminated by sponsor	0	1	0	0	0	0	1	0	0
Withdrew: Withdrawal by subject	0	0	0	1	0	2	0	3	1
Withdrew: Physician decision	0	0	0	0	0	1	0	0	0

Outcome measures

PrimaryPhase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug. A SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug will be determined by the Investigator.

Time frame:: First dose of study drug through 30 days after the last dose (Up to 52 months)
Reported as:: Count of participants · Participants

Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants	Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane
Any AE	6	6	3	3	6
SAEs	1	2	0	0	2

PrimaryPhase 2: Clinical Benefit Rate at 16 Weeks (CBR-16)

CBR-16 was defined as the percentage of participants who achieved confirmed complete response (CR) or partial response (PR) of any duration or had confirmed stable disease (SD) as best response and the first 2 or more post baseline scans had PR/SD and the duration of SD was \>112 days. Disease response was assessed for target lesions by computed tomography (CT) or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. CR is disappearance of all target lesions. PR is \>=30% decrease in the sum of the longest diameter of target lesions. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression (PD).

Time frame:: Week 16
Reported as:: Number · percentage of participants

Phase 2: Clinical Benefit Rate at 16 Weeks (CBR-16)
percentage of participants	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)
Phase 2: Clinical Benefit Rate at 16 Weeks (CBR-16)	44 (29.1 to 60.1)	50 (15.7 to 84.3)	23 (10.4 to 40.1)	25 (3.2 to 65.1)

SecondaryPhase 2: Clinical Benefit Rate at 24 Weeks (CBR-24)

CBR-24 was defined as the percentage of participants who achieved confirmed CR or PR at any time or had confirmed SD as best response and the first 2 or more post baseline scans had PR/SD and the duration of stable disease was \>168 days. Disease response was assessed for target lesions by CT or MRI according to RECIST version 1.1 guidelines. CR is disappearance of all target lesions. PR is \>=30% decrease in the sum of the longest diameter of target lesions. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Time frame:: Week 24
Reported as:: Number · percentage of participants

Phase 2: Clinical Benefit Rate at 24 Weeks (CBR-24)
percentage of participants	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)
Phase 2: Clinical Benefit Rate at 24 Weeks (CBR-24)	28 (15.3 to 43.7)	38 (8.5 to 75.5)	23 (10.4 to 40.1)	25 (3.2 to 65.1)

SecondaryPhase 2: Overall Response Rate (ORR)

ORR is defined as the percentage of participants with confirmed CR or PR as per RECIST version1.1 guidelines. CR is disappearance of all target lesions. PR is \>=30% decrease in the sum of the longest diameter of target lesions.

Time frame:: Baseline then every 2 cycles from Cycles 2 through 6, and every 3 cycles thereafter in a 28-day cycle up to End of Treatment (EOT) (Up to 24 months)
Reported as:: Number · percentage of participants

Phase 2: Overall Response Rate (ORR)
percentage of participants	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)
Phase 2: Overall Response Rate (ORR)	7 (1.5 to 19.1)	13 (1 to 52.7)	0 (0 to 0)	13 (1 to 52.7)

SecondaryPhase 2: Progression-Free Survival (PFS)

PFS is defined as the time in months from the date of first dose of study treatment to the date of the first documented disease progression or death. Disease progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; or the appearance of one or more new lesions.

Time frame:: Baseline then every 2 cycles from Cycles 2 through 6, and every 3 cycles thereafter in a 28-day cycle, then every 3 months after EOT until disease progression or death (Up to 24 months)
Reported as:: Median · months

Phase 2: Progression-Free Survival (PFS)
months	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)
Phase 2: Progression-Free Survival (PFS)	4.1 (1.9 to 5.5)	5.5 (1.8 to NA)	3.3 (1.9 to 3.7)	5.4 (1.7 to 8.3)

SecondaryPhase 2: Overall Survival (OS)

OS is the time in months from start of study treatment to date of death due to any cause. Data for the analysis of OS included the censored data at the timepoint that the participant was last known to be alive.

Time frame:: Up to 24 months
Reported as:: Median · months

Phase 2: Overall Survival (OS)
months	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)
Phase 2: Overall Survival (OS)	15.9 (14.1 to 19.5)	20.7 (8.6 to 20.7)	14.0 (10.6 to 16.0)	13.0 (4.1 to 21.3)

SecondaryPhase 2: Best Percent Change From Baseline in Tumor Size

Time frame:: Baseline to Month 24
Reported as:: Mean · percentage change in tumor size

Phase 2: Best Percent Change From Baseline in Tumor Size
percentage change in tumor size	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)
Phase 2: Best Percent Change From Baseline in Tumor Size	-0.46 ± 34.89	0.96 ± 38.98	1.76 ± 31.14	-18.91 ± 19.71

SecondaryPhase1: Cmax: Maximum Observed Plasma Concentration for Sapanisertib

Time frame:: Cycle 1 Day 15 and Cycle 2 Day 1 pre-dose and multiple timepoints (Up to 8 hours) post-dose
Reported as:: Mean · ng/mL

Phase1: Cmax: Maximum Observed Plasma Concentration for Sapanisertib
ng/mL	Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane
Cycle 1 Day 15	57.72 ± 9.927	—	47.40 ± 6.583	50.90 ± 23.476	45.37 ± 9.644
Cycle 2 Day 1	38.68 ± 20.551	44.96 ± 34.459	43.47 ± 0.874	45.30 ± 16.235	44.68 ± 8.636

SecondaryPhase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Sapanisertib

Time frame:: Cycle 1 Day 15 and Cycle 2 Day 1 pre-dose and multiple timepoints (Up to 8 hours) post-dose
Reported as:: Median · hour

Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Sapanisertib
hour	Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane
Cycle 1 Day 15	3.005 (0.58 to 7.30)	—	0.600 (0.45 to 1.00)	1.035 (1.00 to 1.07)	2.000 (0.50 to 3.55)
Cycle 2 Day 1	2.280 (0.85 to 3.58)	3.500 (0.92 to 4.03)	0.980 (0.68 to 1.00)	1.000 (0.48 to 1.12)	2.000 (0.50 to 3.77)

SecondaryPhase 1: AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for Sapanisertib

AUC(0-24) is the area under the plasma concentration-time curve of the samples collected up to 8 hours and extrapolated up to 24 hours.

Time frame:: Cycle 1 Day 15 pre-dose and multiple timepoints (Up to 8 hours) post-dose, extrapolated to 24 hours post-dose
Reported as:: Mean · h*ng/mL

Phase 1: AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for Sapanisertib
h*ng/mL	Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane
Phase 1: AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours for Sapanisertib	577.081 ± 331.9813	—	178.063 ± 46.1416	332.618 ± 228.5641	277.626 ± 64.0661

SecondaryPhase 1: AUC(0-last): Area Under the Plasma Concentration-time Curve From Time 0 to Last Extrapolated Concentration Over the Dosing Interval for Sapanisertib

AUC(0-last) is the area under the plasma concentration-time curve of the samples collected up to 8 hours and extrapolated up to last time point.

Time frame:: Cycle 1 Day 15 pre-dose and multiple timepoints (Up to 8 hours) post-dose, extrapolated to last timepoint
Reported as:: Mean · h*ng/mL

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
h*ng/mL	Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane
Cycle 1 Day 15	577.081 ± 331.9813	—	164.123 ± 52.6287	332.618 ± 228.5641	251.165 ± 83.7121
Cycle 1 Day 2	101.599 ± 51.0248	109.496 ± 82.3968	89.576 ± 15.0117	109.548 ± 52.8500	116.557 ± 8.6059

SecondaryPhase 1: Terminal Elimination Half-life (T1/2) for Sapanisertib

Time frame:: Cycle 1 Day 15 pre-dose and multiple timepoints (Up to 8 hours) post-dose
Reported as:: Mean · hour

Phase 1: Terminal Elimination Half-life (T1/2) for Sapanisertib
hour	Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane
Phase 1: Terminal Elimination Half-life (T1/2) for Sapanisertib	6.639 ± 1.2176	—	3.161 ± 1.6585	7.777 ± 2.9177	5.370 ± 1.4638

Adverse events

Collected over From first dose of study drug through 30 days after the last dose (Up to 52 months). Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	0/6 (0%)	1/6 (16.7%)	6/6 (100%)
Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	0/6 (0%)	2/6 (33.3%)	6/6 (100%)
Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	0/3 (0%)	0/3 (0%)	3/3 (100%)
Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	0/3 (0%)	0/3 (0%)	3/3 (100%)
Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane	1/6 (16.7%)	2/6 (33.3%)	6/6 (100%)
Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	0/43 (0%)	11/43 (25.6%)	43/43 (100%)
Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	0/35 (0%)	5/35 (14.3%)	35/35 (100%)
Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	0/8 (0%)	3/8 (37.5%)	8/8 (100%)
Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)	0/8 (0%)	2/8 (25%)	8/8 (100%)

Most frequent serious events

Showing 10 of 37

Most frequent serious events
Event	Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)
PneumoniaInfections and infestations	1/6	0/6	0/3	0/3	0/6	0/43	0/35	0/8	0/8
SepsisInfections and infestations	1/6	0/6	0/3	0/3	0/6	0/43	0/35	0/8	0/8
Upper respiratory tract infectionInfections and infestations	0/6	1/6	0/3	0/3	0/6	0/43	0/35	0/8	0/8
Viral infectionInfections and infestations	0/6	1/6	0/3	0/3	0/6	0/43	0/35	0/8	0/8
DyspnoeaRespiratory, thoracic and mediastinal disorders	0/6	0/6	0/3	0/3	1/6	0/43	0/35	0/8	0/8
PneumonitisRespiratory, thoracic and mediastinal disorders	0/6	1/6	0/3	0/3	0/6	0/43	0/35	0/8	0/8
Abdominal painGastrointestinal disorders	0/6	0/6	0/3	0/3	1/6	1/43	0/35	0/8	0/8
Hepatic failureHepatobiliary disorders	0/6	0/6	0/3	0/3	1/6	0/43	0/35	0/8	0/8
AtaxiaNervous system disorders	1/6	0/6	0/3	0/3	0/6	0/43	0/35	0/8	0/8
Mental status changesPsychiatric disorders	1/6	0/6	0/3	0/3	0/6	1/43	0/35	0/8	0/8

Most frequent other events

Showing 10 of 285

Most frequent other events
Event	Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)
NauseaGastrointestinal disorders	6/6	4/6	1/3	2/3	3/6	23/43	15/35	7/8	4/8
DyspepsiaGastrointestinal disorders	2/6	1/6	3/3	0/3	0/6	4/43	1/35	0/8	0/8
FatigueGeneral disorders	4/6	6/6	1/3	3/3	4/6	19/43	16/35	6/8	2/8
PruritusSkin and subcutaneous tissue disorders	3/6	3/6	1/3	3/3	3/6	11/43	6/35	1/8	1/8
DiarrhoeaGastrointestinal disorders	3/6	5/6	2/3	2/3	4/6	17/43	9/35	3/8	6/8
StomatitisGastrointestinal disorders	5/6	3/6	0/3	0/3	2/6	10/43	8/35	3/8	2/8
Abdominal painGastrointestinal disorders	0/6	0/6	2/3	0/3	1/6	5/43	2/35	1/8	0/8
HyperglycaemiaMetabolism and nutrition disorders	3/6	4/6	0/3	0/3	1/6	11/43	16/35	0/8	4/8
ArthralgiaMusculoskeletal and connective tissue disorders	2/6	1/6	2/3	0/3	0/6	3/43	2/35	2/8	1/8
VomitingGastrointestinal disorders	1/6	2/6	1/3	0/3	3/6	10/43	10/35	1/8	5/8

Baseline characteristics

Safety Population was defined as all participants who received at least 1 dose of any study drug.

Age, Continuous
Age, Continuous(years)	Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)	Total
Mean	61.3 (52 to 74)	56.2 (42 to 67)	54.0 (39 to 62)	52.3 (48 to 56)	59.5 (33 to 75)	58.9 (37 to 83)	52.1 (32 to 73)	58.8 (33 to 74)	58.5 (47 to 70)	57.31 (32 to 83)

Sex: Female, Male
Sex: Female, Male(Participants)	Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)	Total
Female	6	6	3	3	6	43	8	35	8	118
Male	0	0	0	0	0	0	0	0	0	0

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)	Total
Hispanic or Latino	0	0	0	0	1	3	0	0	0	4
Not Hispanic or Latino	6	6	3	3	5	36	8	29	7	103
Unknown or Not Reported	0	0	0	0	0	4	0	6	1	11

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)	Total
White	6	5	2	2	6	36	8	25	8	98
Not Reported	0	0	0	0	0	1	0	5	0	6
Black or African American	0	0	1	1	0	4	0	1	0	7
Asian	0	1	0	0	0	0	0	3	0	4
Other	0	0	0	0	0	2	0	1	0	3

Region of Enrollment
Region of Enrollment(Participants)	Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)	Total
United States	6	6	3	3	6	30	8	25	8	95
Belgium	0	0	0	0	0	9	0	7	0	16
France	0	0	0	0	0	4	0	3	0	7

Height
Height(cm)	Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)	Total
Mean	167.1 (160 to 177)	165.7 (159 to 175)	167.0 (160 to 175)	170.8 (166.4 to 176)	161.1 (155 to 165)	163.5 (152 to 179)	165.7 (158 to 175)	164.5 (150 to 183)	163.7 (154 to 177)	165.02 (150 to 183)

Weight
Weight(kg)	Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane	Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane	Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant	Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)	Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Resistant)	Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)	Total
Mean	69.18 (52.0 to 93.0)	69.45 (52.6 to 120.2)	70.57 (57.2 to 77.7)	64.34 (59.5 to 69.4)	63.63 (54.9 to 77.1)	72.10 (47.2 to 123.7)	67.45 (46.5 to 90.5)	71.60 (50.0 to 114.0)	82.10 (49.8 to 139.0)	70.37 (46.5 to 139)

Study locations

40 sites

Los Angeles Hematology
Los Angeles, California 90017, United States
University of California at San Francisco (PARENT)
San Francisco, California 94143, United States
Santa Barbara Hematology Oncology Medical Group, Inc.
Santa Barbara, California 93105, United States
University of Colorado Cancer Center
Aurora, Colorado 80045, United States
Rocky Mountain Cancer Centers, LLP
Lakewood, Colorado 80228, United States
Mount Sinai Medical Center
Miami Beach, Florida 33140, United States
Florida Cancer Research Institute
Plantation, Florida 33324, United States
University of Kansas Medical Center Research Institute, Inc.
Westwood, Kansas 66205, United States
Holy Cross Hospital
Silver Spring, Maryland 20910, United States
Henry Ford Medical Center
Novi, Michigan 48322, United States
University of Minnesota
Minneapolis, Minnesota 55455, United States
Mayo Clinic
Rochester, Minnesota 55905, United States
Eastchester Center for Cancer Care / BRANY
Bronx, New York 10469, United States
Roswell Park Cancer Institute
Buffalo, New York 14263-0001, United States
Herbert Irving Comprehensive Cancer Center
New York, New York 10032, United States
Weill Cornell Medical College New York Presbyterian Hospital
New York, New York 10065, United States
University of Cincinnati Physicians Company, LLC
Cincinnati, Ohio 45267-0502, United States
University Hospitals of Cleveland
Cleveland, Ohio 44106, United States
Erlanger Medical Center
Chattanooga, Tennessee 37403, United States
Texas Oncology, P.A. - Beaumont
Beaumont, Texas 77702-1449, United States
Texas Oncology, P.A.
Dallas, Texas 75246, United States
UT Southwestern Medical Center
Dallas, Texas 75390-9085, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas 77030, United States
Millennium Oncology
Houston, Texas 77090, United States
Texas Health Physicians Group
Plano, Texas 75093, United States
Cancer Care Network of South Texas - SAT&BC
San Antonio, Texas 78217, United States
Texas Oncology, P.A. - Tyler
Tyler, Texas 75702, United States
Virginia Oncology Associates - Hampton
Chesapeake, Virginia 23320, United States
Oncology and Hematology Assoc. of SW VA, Inc.
Salem, Virginia 24153, United States
West Virginia University
Morgantown, West Virginia 26506, United States
UZ Antwerpen
Antwerpen, 2650, Belgium
Institut Jules Bordet
Bruxelles, 1000, Belgium
Universitair Ziekenhuis Brussel
Bruxelles, 1090, Belgium
GHdC Notre Dame
Charleroi, 6000, Belgium
Centre Hospitalier de l'Ardenne
Libramont, 6800, Belgium
GZA Ziekenhuizen - Campus Sint-Augustinus
Wilrijk, 2610, Belgium
Centre Francois Baclesse
Caen Cedex 05, Calvados 14076, France
Centre Catherine de Sienne
Nantes, Loire Atlantique 44202, France
Clinique Victor Hugo - Centre Jean Bernard
Le Mans Cedex 02, Sarthe 72015, France
Institut Sainte Catherine
Avignon, Vaculuse 84000, France

References and documents

Publications

Lim B, Potter DA, Salkeni MA, Silverman P, Haddad TC, Forget F, Awada A, Canon JL, Danso M, Lortholary A, Bourgeois H, Tan-Chiu E, Vincent S, Bahamon B, Galinsky KJ, Patel C, Neuwirth R, Leonard EJ, Diamond JR. Sapanisertib Plus Exemestane or Fulvestrant in Women with Hormone Receptor-Positive/HER2-Negative Advanced or Metastatic Breast Cancer. Clin Cancer Res. 2021 Jun 15;27(12):3329-3338. doi: 10.1158/1078-0432.CCR-20-4131. Epub 2021 Apr 5. PubMed 33820779 ↗

Study documents

Study protocol · Oct 26, 2017
Statistical analysis plan · Jul 23, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting information: Study protocol, Sap, Icf, Csr

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Feb 8, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02049957
Lead sponsor: Calithera Biosciences, Inc
Responsible party: Sponsor
First posted: Jan 30, 2014
Start date: Feb 13, 2014
Primary completion: Jun 29, 2018
Completion: Jun 29, 2018
Results posted: Jan 27, 2020
Last update: Feb 8, 2023

Study contacts

Medical Monitor

study director · Millennium Pharmaceuticals, Inc.

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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