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

NCT02049957 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: C310012014-001921-34U1111-1195-3894
• Study Type: interventional
• Target: 118
• Locations: 3 countries
• Sites: 40

Brief 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.

Conditions

Breast Cancer

Keywords

Sapanisertib; MLN0128

Outcome Measures

Primary Outcomes (2)

• 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.

  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).

  Week 16

Secondary Outcomes (10)

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

  Week 24

• Phase 2: Overall Response Rate (ORR)

  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)

  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)

  Up to 24 months

• Phase 2: Best Percent Change From Baseline in Tumor Size

  Baseline to Month 24

Study Arms (9)

Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane

EXPERIMENTAL

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

Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant

EXPERIMENTAL

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

Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane

EXPERIMENTAL

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

Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant

EXPERIMENTAL

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

Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane

EXPERIMENTAL

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

Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive)

EXPERIMENTAL

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

Phase 2:Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)

EXPERIMENTAL

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

Phase 2: Sapanisertib 4 mg+Exemestane (Everolimus Resistant)

EXPERIMENTAL

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

Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant)

EXPERIMENTAL

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

Sapanisertib DRUG

Sapnisertib capsules

Also known as: MLN0128

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 Resistant); Phase 2:Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)

Fulvestrant DRUG

Fulvestrant IM injection.

Phase 1 (Part 1): Sapanisertib 5 mg + Fulvestrant; Phase 1 (Part 2): Sapanisertib 3 mg + Fulvestrant; Phase 2: Sapanisertib 4 mg+Fulvestrant (Everolimus Resistant); Phase 2:Sapanisertib 4 mg+Fulvestrant (Everolimus Sensitive)

Exemestane DRUG

Exemestane tablets.

Phase 1 (Part 1): Sapanisertib 5 mg + Exemestane; Phase 1 (Part 2): Sapanisertib 3 mg + Exemestane; Phase 1 (Part 2): Sapanisertib 4 mg + Exemestane; Phase 2: Sapanisertib 4 mg + Exemestane (Everolimus Sensitive); Phase 2: Sapanisertib 4 mg+Exemestane (Everolimus Resistant)

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Postmenopausal Women With ER/PR+ Metastatic Breast Cancer.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Calithera Biosciences, Inc: lead

Study Sites (40)

Los Angeles Hematology

Los Angeles, California, 90017, United States

Location

University of California at San Francisco (PARENT)

San Francisco, California, 94143, United States

Location

Santa Barbara Hematology Oncology Medical Group, Inc.

Santa Barbara, California, 93105, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Cancer Centers, LLP

Lakewood, Colorado, 80228, United States

Location

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Florida Cancer Research Institute

Plantation, Florida, 33324, United States

Location

University of Kansas Medical Center Research Institute, Inc.

Westwood, Kansas, 66205, United States

Location

Holy Cross Hospital

Silver Spring, Maryland, 20910, United States

Location

Henry Ford Medical Center

Novi, Michigan, 48322, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Weill Cornell Medical College New York Presbyterian Hospital

New York, New York, 10065, United States

Location

Eastchester Center for Cancer Care / BRANY

The Bronx, New York, 10469, United States

Location

University of Cincinnati Physicians Company, LLC

Cincinnati, Ohio, 45267-0502, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Erlanger Medical Center

Chattanooga, Tennessee, 37403, United States

Location

Texas Oncology, P.A. - Beaumont

Beaumont, Texas, 77702-1449, United States

Location

Texas Oncology, P.A.

Dallas, Texas, 75246, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390-9085, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Millennium Oncology

Houston, Texas, 77090, United States

Location

Texas Health Physicians Group

Plano, Texas, 75093, United States

Location

Cancer Care Network of South Texas - SAT&BC

San Antonio, Texas, 78217, United States

Location

Texas Oncology, P.A. - Tyler

Tyler, Texas, 75702, United States

Location

Virginia Oncology Associates - Hampton

Chesapeake, Virginia, 23320, United States

Location

Oncology and Hematology Assoc. of SW VA, Inc.

Salem, Virginia, 24153, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

UZ Antwerpen

Antwerp, 2650, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Universitair Ziekenhuis Brussel

Brussels, 1090, Belgium

Location

GHdC Notre Dame

Charleroi, 6000, Belgium

Location

Centre Hospitalier de l'Ardenne

Libramont, 6800, Belgium

Location

GZA Ziekenhuizen - Campus Sint-Augustinus

Wilrijk, 2610, Belgium

Location

Centre Francois Baclesse

Caen, Calvados, 14076, France

Location

Centre Catherine de Sienne

Nantes, Loire Atlantique, 44202, France

Location

Clinique Victor Hugo - Centre Jean Bernard

Le Mans, Sarthe, 72015, France

Location

Institut Sainte Catherine

Avignon, Vaculuse, 84000, France

Location

Related Publications (1)

• 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.

  PMID: 33820779 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

sapanisertib; Fulvestrant; exemestane

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Monitor

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2013
• First Posted: January 30, 2014
• Study Start: February 13, 2014
• Primary Completion: June 29, 2018
• Study Completion: June 29, 2018
• Last Updated: February 8, 2023
• Results First Posted: January 27, 2020

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

BE (6); FR (4); US (30)