SHERBOC: Phase 2 Trial of Seribantumab Plus Fulvestrant in Postmenopausal Women With Metastatic Breast Cancer

Sponsor
Elevation Oncology (Industry)
Overall Status
Terminated
CT.gov ID
NCT03241810
Collaborator
(none)
22
60
2
15.5
0.4
0

Study Details

Study Description

Brief Summary

This study is a multi-center, randomized, double-blind, placebo-controlled, Phase 2 study in postmenopausal women with heregulin positive, hormone receptor positive, HER2 negative metastatic, unresectable breast cancer.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This study is a randomized, double-blind, placebo-controlled international phase 2 trial in patients with HRG+, HR+, HER2- metastatic breast cancer that has progressed following treatment with no more than 2 prior therapies, one of which must have been a CDK inhibitor. All patients will be screened for heregulin using central testing, and eligible patients will be randomized to receive either seribantumab + fulvestrant or placebo + fulvestrant. Disease status will be assessed according to RECIST v 1.1 to support the primary endpoint.

Study Design

Study Type:
Interventional
Actual Enrollment :
22 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Patients will be randomized in a 1:1 ratio (experimental arm versus active comparator arm) using an Interactive Web Response System (IWRS). Randomization will be stratified based on bone-only disease (yes, no) and geographic region (US, non-US).Patients will be randomized in a 1:1 ratio (experimental arm versus active comparator arm) using an Interactive Web Response System (IWRS). Randomization will be stratified based on bone-only disease (yes, no) and geographic region (US, non-US).
Masking:
Triple (Participant, Care Provider, Investigator)
Masking Description:
This is a multi-center, randomized, double-blind, placebo-controlled Phase 2 Study.
Primary Purpose:
Treatment
Official Title:
Randomized Phase 2 Trial of Seribantumab Plus Fulvestrant in Postmenopausal Women With Hormone Receptor-positive, Heregulin Positive (HRG+), HER2 Negative Metastatic Breast Cancer (Merrimack Pharmaceuticals Inc.)
Actual Study Start Date :
Aug 15, 2017
Actual Primary Completion Date :
Nov 30, 2018
Actual Study Completion Date :
Nov 30, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A

Seribantumab Fulvestrant

Drug: Seribantumab
Seribantumab is a human monoclonal antibody that inhibits ErbB3 signalling
Other Names:
  • MM-121
  • Drug: Fulvestrant
    Fulvestrant is an estrogen receptor antagonist with no agonist effects
    Other Names:
  • Faslodex
  • Active Comparator: Arm B

    Placebo Fulvestrant

    Drug: Fulvestrant
    Fulvestrant is an estrogen receptor antagonist with no agonist effects
    Other Names:
  • Faslodex
  • Drug: Placebo
    Placebo
    Other Names:
  • Solution containing 20 mM histidine, 150 mM sodium chloride, at a pH of 6.5
  • Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival [Randomization until progression of disease or death due to any cause up to 13 months (The study terminated prematurely) . The primary analysis was planned to be initiated when 58 PFS events have occurred]

      Progression Free Survival is defined as the time from randomization to the first documented radiographical progression of disease using RECIST v1.1 or death from any cause, whichever comes first as assessed by the investigator. The tumor assessment (i.e., scan dates) was used for progression/censor date not the date corresponding to the determination of overall response. Progression-free survival time distribution and median survival for each treatment group were analyzed using the Kaplan-Meier method.

    Secondary Outcome Measures

    1. Overall Survival [Randomization until death due to any cause up to 13 months (The study terminated prematurely)]

      Overall Survival (OS) is defined as the time from the date of randomization to the date of death from any cause. The study was terminated on 30 Nov 2018 . Data represents outcomes up to 150 days of treatment.

    2. Objective Response Rate [Randomization through end of study up to 13 months (The study terminated prematurely)]

      Objective Response Rate (ORR) is defined as the proportion of patients with a RECIST v1.1 response recorded from randomization until disease progression characterized as either a Complete Response (CR) or Partial Response (PR) relative to the total number of evaluable patients.

    3. Time to Progression [Randomization to date of objective tumor progression up to 13 months (The study terminated prematurely)]

      Time to Progression (TTP) is defined as the time from the date of randomization to the date of objective tumor progression.

    4. Number of Participants With Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone [TEAEs were collected through the study completion (30 Nov 2018), up to 13 months. Frequency and percent summaries were presented for TEAE defined as adverse events that occur or worsen in severity following the first dose of seribantumab, or fulvestrant]

      Treatment-emergent adverse events (TEAEs) are defined as any event that occurred after the first dose of study drug and was not present prior to study drug administration or worsened in severity after study drug administration.

    5. Percentage of Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone [TEAEs were collected through the study completion (30 Nov 2018), up to 13 months. Frequency and percent summaries were presented for TEAE defined as adverse events that occur or worsen in severity following the first dose of seribantumab, or fulvestrant]

      Treatment-emergent adverse events (TEAEs) are defined as any event that occurred after the first dose of study drug and was not present prior to study drug administration or worsened in severity after study drug administration.

    6. Pharmacokinetic (PK) Profile of Seribantumab When Given in Combination With Fulvestrant and of Fulvestrant When Given in Combination With Serbantumab. [The study terminated prematurely after 13 months. Were to be analyzed post-dose on Cycle 1,Week 1 & pre-dose for all subsequent seribantumab infusions until the completion of Cycle 2. Fulvestrant PK samples were to be collected prior to seribantumab dose]

      Pharmacokinetic (PK) evaluation are performed on samples obtained pre-dose on day 1 and 15 of each 28-day cycle to assess pre-treatment trough concentrations of MM-121. The maximum observed concentration (Cmax) is presented and calculated usig Non-compartmental analysis (NCA). Serum levels of MM-121 are measured at a central lab using an enzyme-linked immunosorbent assay (ELISA).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    To be eligible for participation in the study, patients must meet the following criteria. Patients who are HRG negative do not need to complete screening procedures beyond HRG assessment.

    1. Patients must have histologically or cytologically confirmed ER+ and/or PR+ (with staining of >1% cells) breast cancer.

    2. Patients with confirmed postmenopausal status due to either surgical/natural menopause or ovarian suppression.

    3. Patients must be HER2 negative.

    4. Patient must have at least one lesion amenable to either core needle biopsy or fine needle aspiration.

    5. Patient must have a positive in-situ hybridization (ISH) test for heregulin, as determined by centralized testing of unstained tumor tissue.

    6. Patients that have progressed following at least one but no more than two prior systemic therapies in the locally advanced or metastatic disease setting.

    7. Patients with documented progression of locally advanced or metastatic disease as defined by RECISTv1.1 (Exception: patients with bone-only metastatic disease are eligible if they have at least 2 lytic lesions visible on a CT or MRI and have documented disease progression on prior therapy based on the appearance of new lesions).

    8. Patients with bone-only lesions who have received radiation to those lesions must have documented progression following radiation therapy.

    9. ECOG Performance Score (PS) of 0 or 1.

    10. Patients with adequate bone marrow reserves.

    11. Adequate hepatic function.

    12. Adequate renal function.

    13. Patient has recovered from clinically significant effects of any prior, surgery, radiosurgery, or other antineoplastic therapy.

    14. Patients who have experienced a venous thromboembolic event within 60 days of signing the main consent form should have been treated with anti-coagulants for at least 7 days prior to beginning treatment and for the duration of treatment on this study.

    Exclusion Criteria:

    Patients must meet all the inclusion criteria listed above and none of the following exclusion criteria.

    1. Prior treatment with an anti-ErbB3 antibody.

    2. Prior treatment with a chemotherapy in the locally advanced or metastatic disease setting.

    3. Patients cannot have received prior treatment with fulvestrant or other SERDs in the locally advanced or metastatic setting.

    4. Uncontrolled CNS disease or presence of leptomeningeal disease.

    5. Inflammatory breast cancer.

    6. History of another active malignancy that required systemic therapy in the last 2 years. Patients with prior history of in-situ cancer, basal, or squamous cell skin cancer are eligible.

    7. Patients with an active infection, or unexplained fever > 38.5 C during screening visits or on the first scheduled day of dosing, which in the investigator's opinion might compromise the patients participation in the trial or affect the study outcome. At the discretion of the investigator, patients with tumor fever may be enrolled.

    8. Known hypersensitivity to any of the components of seribantumab, fulvestrant, or who have had hypersensitivity reactions to fully human monoclonal antibodies.

    9. NYHA Class III or IV congestive heart failure.

    10. Patients with a significant history of cardiac disease (i.e. uncontrolled blood pressure, unstable angina, myocardial infarction within 1 year or ventricular arrhythmias requiring medication) are also excluded.

    11. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; or active human immunodeficiency virus (HIV) infection, active hepatitis B infection or active hepatitis C infection.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ironwood Cancer and Research Centers- Chandler Chandler Arizona United States 85224
    2 Highland Oncology Group Fayetteville Arkansas United States 72703
    3 Beverly Hills Cancer Center Beverly Hills California United States 90404-2131
    4 Stanford University Palo Alto California United States 94304
    5 Saint Helena Hospital Saint Helena California United States 94574
    6 Stamford Hospital Stamford Connecticut United States 06902-3628
    7 Sylvester Comprehensive Cancer Center Miami Florida United States 33136
    8 UF Health Cancer Center at Orlando Health Orlando Florida United States 32806
    9 Moffitt Cancer Center Tampa Florida United States 33612
    10 Columbus Regional Research Institute Columbus Georgia United States 31904
    11 Cancer Care Specialists of Central Illinois Decatur Illinois United States 62526
    12 James M Stockman Cancer Institute Frederick Maryland United States 21701
    13 Holy Cross Hospital Health Center Silver Spring Maryland United States 20902
    14 Lahey Clinical Medical Center Burlington Massachusetts United States 01805
    15 University of Mississippi Jackson Mississippi United States 39216
    16 Mercy Hospital Springfield Springfield Missouri United States 65804
    17 Saint Francis Cancer Treatment Center Grand Island Nebraska United States 68803
    18 Dartmouth Hitchcock Medical Center Lebanon New Hampshire United States 03756
    19 Lineberger Comprehensive Cancer Center Chapel Hill North Carolina United States 27599
    20 Oncology Specialists of Charlotte Charlotte North Carolina United States 28207
    21 UPMC Cancer Center Pittsburgh Pennsylvania United States 15232
    22 University of Utah Health Care - Huntsman Cancer Institute Salt Lake City Utah United States 84112
    23 LKH - Universitätsklinikum Graz Graz Austria 8036
    24 Universitaetsklinik fuer Gynaekologie und Geburtshilfe Innsbruck Austria 6020
    25 Krankenhaus der Barmherzigen Schwestern Linz Linz Austria 4010
    26 Medizinische Universität Wien Vienna Austria 1090
    27 Medizinische Universität Wien Wien Austria 1090
    28 Clinique Saint-Pierre Ottignies Brabant Wallon Belgium 1340
    29 Centre Hospitalier de l'Ardenne - Clinique du Sein Libramont Luxembourg Belgium 6800
    30 Universitaire Ziekenhuis Leuven Leuven Vlaams Brabant Belgium 3000
    31 Universitair Ziekenhuis Antwerpen Antwerp Belgium 2650
    32 Cliniques Universitaires Saint-Luc Brussels Belgium 1200
    33 CHU UCL NAMUR - Sainte Elisabeth Namur Belgium 5000
    34 University of Calgary Calgary Alberta Canada T2S 3C3
    35 British Columbia Cancer Agency Kelowna British Columbia Canada V1Y 5L3
    36 McGill University - Jewish General Hospital Montreal Canada H3T 1E2
    37 Centre Hospitalier Affilie Universitaire de Quebec Quebec Canada G1S 4L8
    38 Universitätsklinikum Erlangen Erlangen Bayern Germany 91054
    39 Medizinisches Zentrum Bonn Friedensplatz Bonn Germany 53111
    40 Centrum fuer Haematologie und Onkologie Bethanien Frankfurt Germany
    41 Gynäkologisch-Onkologische Praxis Hannover Hannover Germany 30177
    42 Rotkreuzklinikum München-Frauenklinik Munich Germany 80637
    43 Klinikum Rechts der Isar der Technischen Universität München München Germany 81675
    44 Onkologie Rheinsieg Troisdorf Germany 53840
    45 Universitätsklinikum Ulm Ulm Germany 89075
    46 Hospital Universitari General de Catalunya Sant Cugat Del Vallès Barcelona Spain 08190
    47 Hospital Teresa Herrera A Coruña Spain 15006
    48 Hospital Universitari de Girona Doctor Josep Trueta Gerona Spain 17007
    49 Complejo Hospitalario de Jaén Jaén Spain 23007
    50 Complejo Hospitalario Universitario La Coruña La Coruña Spain 15006
    51 Hospital Universitari Arnau de Vilanova Lleida Spain 25198
    52 Hospital General Universitario Gregorio Marañón Madrid Spain 28007
    53 Hospital Universitario Ramón Y Cajal Madrid Spain 28034
    54 Hospital Clínico San Carlos Madrid Spain 28040
    55 Hospital Universitario La Paz Madrid Spain 28046
    56 Hospital Universitario Virgen de la Victoria Málaga Spain 29010
    57 Hospital Son Llatzer Palma de Mallorca Spain 07198
    58 De La Cruz Merino, Luis Sevilla Spain 41009
    59 Hospital Clínico Universitario de Valencia Valencia Spain 46010
    60 Hospital Universitario Miguel Servet Zaragoza Spain 59009

    Sponsors and Collaborators

    • Elevation Oncology

    Investigators

    • Study Director: Marc Pipas, MD, Merrimack Pharmaceuticals Inc.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Elevation Oncology
    ClinicalTrials.gov Identifier:
    NCT03241810
    Other Study ID Numbers:
    • MM-121-02-02-10
    • 2017-000565-76
    First Posted:
    Aug 8, 2017
    Last Update Posted:
    Sep 2, 2020
    Last Verified:
    Nov 1, 2019
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Elevation Oncology
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details At the time of the study termination by the prior Sponsor (Merrimack Pharmaceuticals), 62 sites participated in the study (27 in North America and 35 in Europe).
    Pre-assignment Detail
    Arm/Group Title Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Arm/Group Description Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
    Period Title: Overall Study
    STARTED 11 11
    COMPLETED 11 11
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant Total
    Arm/Group Description Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle Total of all reporting groups
    Overall Participants 11 11 22
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    8
    72.7%
    7
    63.6%
    15
    68.2%
    >=65 years
    3
    27.3%
    4
    36.4%
    7
    31.8%
    Sex: Female, Male (Count of Participants)
    Female
    11
    100%
    11
    100%
    22
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    11
    100%
    11
    100%
    22
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    9.1%
    0
    0%
    1
    4.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    1
    9.1%
    1
    4.5%
    White
    10
    90.9%
    9
    81.8%
    19
    86.4%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    1
    9.1%
    1
    4.5%
    Region of Enrollment (Number) [Number]
    Canada
    0
    0%
    1
    9.1%
    1
    4.5%
    Belgium
    2
    18.2%
    1
    9.1%
    3
    13.6%
    United States
    5
    45.5%
    6
    54.5%
    11
    50%
    Spain
    4
    36.4%
    3
    27.3%
    7
    31.8%
    Metastatic burden (TNM Stage at Initial Diagnosis) (Number) [Number]
    TNM Stage I
    0
    0%
    1
    9.1%
    1
    4.5%
    TNM Stage II
    0
    0%
    2
    18.2%
    2
    9.1%
    TNM Stage IIa
    4
    36.4%
    0
    0%
    4
    18.2%
    TNM Stage IIb
    1
    9.1%
    0
    0%
    1
    4.5%
    TNM Stage III
    0
    0%
    2
    18.2%
    2
    9.1%
    TNM Stage IIIa
    1
    9.1%
    0
    0%
    1
    4.5%
    TNM Stage IIIc
    1
    9.1%
    0
    0%
    1
    4.5%
    TNM Stage IV
    4
    36.4%
    6
    54.5%
    10
    45.5%
    Heregulin positive status and staining in archival tissue (Count of Participants)
    Count of Participants [Participants]
    11
    100%
    11
    100%
    22
    100%

    Outcome Measures

    1. Primary Outcome
    Title Progression Free Survival
    Description Progression Free Survival is defined as the time from randomization to the first documented radiographical progression of disease using RECIST v1.1 or death from any cause, whichever comes first as assessed by the investigator. The tumor assessment (i.e., scan dates) was used for progression/censor date not the date corresponding to the determination of overall response. Progression-free survival time distribution and median survival for each treatment group were analyzed using the Kaplan-Meier method.
    Time Frame Randomization until progression of disease or death due to any cause up to 13 months (The study terminated prematurely) . The primary analysis was planned to be initiated when 58 PFS events have occurred

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat (ITT) population treated up to 150 days
    Arm/Group Title Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Arm/Group Description Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
    Measure Participants 11 11
    Number [Participants]
    1
    9.1%
    1
    9.1%
    2. Secondary Outcome
    Title Overall Survival
    Description Overall Survival (OS) is defined as the time from the date of randomization to the date of death from any cause. The study was terminated on 30 Nov 2018 . Data represents outcomes up to 150 days of treatment.
    Time Frame Randomization until death due to any cause up to 13 months (The study terminated prematurely)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat (ITT) population treated up to 150 days
    Arm/Group Title Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Arm/Group Description Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
    Measure Participants 11 11
    Number [participants]
    1
    9.1%
    1
    9.1%
    3. Secondary Outcome
    Title Objective Response Rate
    Description Objective Response Rate (ORR) is defined as the proportion of patients with a RECIST v1.1 response recorded from randomization until disease progression characterized as either a Complete Response (CR) or Partial Response (PR) relative to the total number of evaluable patients.
    Time Frame Randomization through end of study up to 13 months (The study terminated prematurely)

    Outcome Measure Data

    Analysis Population Description
    Incomplete data for all subjects due to length of time on study treatment and frequency of scanning. All patients analysed had progressive disease. Therefore, they did not meet the criteria for ORR and hence could not be evaluated for CR or PR
    Arm/Group Title Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Arm/Group Description Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
    Measure Participants 0 0
    4. Secondary Outcome
    Title Time to Progression
    Description Time to Progression (TTP) is defined as the time from the date of randomization to the date of objective tumor progression.
    Time Frame Randomization to date of objective tumor progression up to 13 months (The study terminated prematurely)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-Treat (ITT) population consisted of all participants randomized to the study.
    Arm/Group Title Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Arm/Group Description Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
    Measure Participants 11 11
    Median (Inter-Quartile Range) [days]
    52
    48
    5. Secondary Outcome
    Title Number of Participants With Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone
    Description Treatment-emergent adverse events (TEAEs) are defined as any event that occurred after the first dose of study drug and was not present prior to study drug administration or worsened in severity after study drug administration.
    Time Frame TEAEs were collected through the study completion (30 Nov 2018), up to 13 months. Frequency and percent summaries were presented for TEAE defined as adverse events that occur or worsen in severity following the first dose of seribantumab, or fulvestrant

    Outcome Measure Data

    Analysis Population Description
    Safety Population: The safety population includes patients receiving at least one dose of study medication. All safety analyses were to be performed on this population.
    Arm/Group Title Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Arm/Group Description Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
    Measure Participants 11 11
    Patients with any TEAE-Related
    7
    63.6%
    4
    36.4%
    Patients with any TEAE-Serious Adverse event
    1
    9.1%
    0
    0%
    NCI-CTCAE Grade 3 or Higher
    2
    18.2%
    1
    9.1%
    6. Secondary Outcome
    Title Percentage of Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone
    Description Treatment-emergent adverse events (TEAEs) are defined as any event that occurred after the first dose of study drug and was not present prior to study drug administration or worsened in severity after study drug administration.
    Time Frame TEAEs were collected through the study completion (30 Nov 2018), up to 13 months. Frequency and percent summaries were presented for TEAE defined as adverse events that occur or worsen in severity following the first dose of seribantumab, or fulvestrant

    Outcome Measure Data

    Analysis Population Description
    Safety Population: The safety population includes patients receiving at least one dose of study medication. All safety analyses were be performed on this population.
    Arm/Group Title Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Arm/Group Description Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
    Measure Participants 11 11
    TEAE-Related
    63.6
    36.4
    TEAE-Serious Adverse event
    9.1
    0
    NCI-CTCAE Grade 3 or Higher
    18.2
    9.1
    7. Secondary Outcome
    Title Pharmacokinetic (PK) Profile of Seribantumab When Given in Combination With Fulvestrant and of Fulvestrant When Given in Combination With Serbantumab.
    Description Pharmacokinetic (PK) evaluation are performed on samples obtained pre-dose on day 1 and 15 of each 28-day cycle to assess pre-treatment trough concentrations of MM-121. The maximum observed concentration (Cmax) is presented and calculated usig Non-compartmental analysis (NCA). Serum levels of MM-121 are measured at a central lab using an enzyme-linked immunosorbent assay (ELISA).
    Time Frame The study terminated prematurely after 13 months. Were to be analyzed post-dose on Cycle 1,Week 1 & pre-dose for all subsequent seribantumab infusions until the completion of Cycle 2. Fulvestrant PK samples were to be collected prior to seribantumab dose

    Outcome Measure Data

    Analysis Population Description
    Due to the premature study termination, the PK data were not collected. There was no pharmacokinetic data feasible for the analysis, and as such, no related analyses were performed. Hence, data could not be reported in the data table.
    Arm/Group Title Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Arm/Group Description Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
    Measure Participants 0 0

    Adverse Events

    Time Frame From Baseline through to premature study completion up to 13 months (30 Nov 2018)
    Adverse Event Reporting Description The safety population includes patients receiving at least one dose of study medication. All safety analyses were be performed on this population. Safety analyses (adverse events and laboratory analyses) were performed using the safety population. Adverse events were coded using the latest MedDRA dictionary (MedDRA 21.0). Severity of adverse events was graded according to the NCI CTCAE version 4.03.
    Arm/Group Title Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Arm/Group Description Seribantumab (a human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, seribantumab is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner): fixed dose of 3000 mg intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle Placebo: intravenously (IV) on day 1 and 15 of each 28-day cycle Fulvestrant: (a drug treatment of hormone receptor-positive metastatic breast cancer in post-menopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and by degrading the estrogen receptor): 500 mg intramuscularly (IM) on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
    All Cause Mortality
    Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 10/11 (90.9%) 10/11 (90.9%)
    Serious Adverse Events
    Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/11 (9.1%) 0/11 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/11 (9.1%) 1 0/11 (0%) 0
    Other (Not Including Serious) Adverse Events
    Arm A (Experimental): Seribantumab and Fulvestrant Arm B (Control): Placebo and Fulvestrant
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 10/11 (90.9%) 8/11 (72.7%)
    Blood and lymphatic system disorders
    Anaemia 2/11 (18.2%) 1/11 (9.1%)
    Cardiac disorders
    Palpitations 1/11 (9.1%) 0/11 (0%)
    Ear and labyrinth disorders
    Ear Pain 1/11 (9.1%) 0/11 (0%)
    Eye disorders
    Dry eye 1/11 (9.1%) 0/11 (0%)
    Eye allergy 1/11 (9.1%) 0/11 (0%)
    Lacrimation increased 1/11 (9.1%) 0/11 (0%)
    Vision blurred 1/11 (9.1%) 0/11 (0%)
    Gastrointestinal disorders
    Diarrhoea 7/11 (63.6%) 3/11 (27.3%)
    Nausea 2/11 (18.2%) 3/11 (27.3%)
    Dyspepsia 3/11 (27.3%) 0/11 (0%)
    Oral pain 2/11 (18.2%) 1/11 (9.1%)
    Abdominal pain 0/11 (0%) 2/11 (18.2%)
    Stomatitis 2/11 (18.2%) 0/11 (0%)
    Constipation 0/11 (0%) 1/11 (9.1%)
    Dry mouth 1/11 (9.1%) 0/11 (0%)
    Dysphagia 1/11 (9.1%) 0/11 (0%)
    Faeces soft 0/11 (0%) 1/11 (9.1%)
    Odynophagia 1/11 (9.1%) 0/11 (0%)
    Salivary hypersecretion 1/11 (9.1%) 0/11 (0%)
    General disorders
    Asthenia 3/11 (27.3%) 1/11 (9.1%)
    Fatigue 2/11 (18.2%) 1/11 (9.1%)
    Chest discomfort 0/11 (0%) 1/11 (9.1%)
    Influenza like illness 1/11 (9.1%) 0/11 (0%)
    Injection site pain 0/11 (0%) 1/11 (9.1%)
    Injection site reaction 0/11 (0%) 1/11 (9.1%)
    Malaise 0/11 (0%) 1/11 (9.1%)
    Pain 0/11 (0%) 1/11 (9.1%)
    Pyrexia 0/11 (0%) 1/11 (9.1%)
    Hepatobiliary disorders
    Hepatomegaly 1/11 (9.1%) 0/11 (0%)
    Infections and infestations
    Urinary tract infection 2/11 (18.2%) 1/11 (9.1%)
    Upper respiratory tract infection 1/11 (9.1%) 1/11 (9.1%)
    Fungal infection 1/11 (9.1%) 0/11 (0%)
    Nasopharyngitis 1/11 (9.1%) 0/11 (0%)
    Injury, poisoning and procedural complications
    Contusion 1/11 (9.1%) 1/11 (9.1%)
    Infusion related reaction 0/11 (0%) 1/11 (9.1%)
    Investigations
    Aspartate aminotransferase increased 0/11 (0%) 1/11 (9.1%)
    Blood alkaline phosphatase increased 0/11 (0%) 1/11 (9.1%)
    Blood bilirubin increased 1/11 (9.1%) 0/11 (0%)
    Blood lactate dehydrogenase increased 0/11 (0%) 1/11 (9.1%)
    White blood cell count decreased 1/11 (9.1%) 0/11 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 3/11 (27.3%) 5/11 (45.5%)
    Hypokalaemia 1/11 (9.1%) 1/11 (9.1%)
    Hypercalcaemia 1/11 (9.1%) 0/11 (0%)
    Hyperchloraemia 1/11 (9.1%) 0/11 (0%)
    Hyperuricaemia 0/11 (0%) 1/11 (9.1%)
    Hypocalcaemia 0/11 (0%) 1/11 (9.1%)
    Hypomagnesaemia 1/11 (9.1%) 0/11 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/11 (18.2%) 1/11 (9.1%)
    Back pain 1/11 (9.1%) 1/11 (9.1%)
    Bone pain 1/11 (9.1%) 1/11 (9.1%)
    Musculoskeletal pain 2/11 (18.2%) 0/11 (0%)
    Flank pain 1/11 (9.1%) 0/11 (0%)
    Groin pain 1/11 (9.1%) 0/11 (0%)
    Joint swelling 0/11 (0%) 1/11 (9.1%)
    Muscle spasms 1/11 (9.1%) 0/11 (0%)
    Myalgia 0/11 (0%) 1/11 (9.1%)
    Neck pain 0/11 (0%) 1/11 (9.1%)
    Pain in extremity 1/11 (9.1%) 0/11 (0%)
    Pain in jaw 0/11 (0%) 1/11 (9.1%)
    Nervous system disorders
    Dysgeusia 2/11 (18.2%) 1/11 (9.1%)
    Headache 2/11 (18.2%) 0/11 (0%)
    Hypoaesthesia 1/11 (9.1%) 1/11 (9.1%)
    Paraesthesia 1/11 (9.1%) 0/11 (0%)
    Psychiatric disorders
    Depression 0/11 (0%) 1/11 (9.1%)
    Irritability 1/11 (9.1%) 0/11 (0%)
    Renal and urinary disorders
    Dysuria 1/11 (9.1%) 1/11 (9.1%)
    Urine odour abnormal 0/11 (0%) 1/11 (9.1%)
    Reproductive system and breast disorders
    Vulvovaginal pruritus 1/11 (9.1%) 0/11 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 2/11 (18.2%) 1/11 (9.1%)
    Cough 1/11 (9.1%) 1/11 (9.1%)
    Epistaxis 1/11 (9.1%) 0/11 (0%)
    Nasal dryness 1/11 (9.1%) 0/11 (0%)
    Oropharyngeal pain 0/11 (0%) 1/11 (9.1%)
    Pleural effusion 0/11 (0%) 1/11 (9.1%)
    Skin and subcutaneous tissue disorders
    Pruritus 2/11 (18.2%) 0/11 (0%)
    Alopecia 1/11 (9.1%) 0/11 (0%)
    Dry skin 1/11 (9.1%) 0/11 (0%)
    Pain of skin 1/11 (9.1%) 0/11 (0%)
    Rash 0/11 (0%) 1/11 (9.1%)
    Rash maculo-papular 1/11 (9.1%) 0/11 (0%)
    Vascular disorders
    Hot flush 2/11 (18.2%) 0/11 (0%)
    Jugular vein thrombosis 0/11 (0%) 1/11 (9.1%)

    Limitations/Caveats

    Sponsor (Merrimack Pharmaceuticals, INC.) terminated the trial early due to business decision

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title VP, Clinical Operations
    Organization Elevation oncology
    Phone +1-716 371 1125
    Email clinical@elevationoncology.com
    Responsible Party:
    Elevation Oncology
    ClinicalTrials.gov Identifier:
    NCT03241810
    Other Study ID Numbers:
    • MM-121-02-02-10
    • 2017-000565-76
    First Posted:
    Aug 8, 2017
    Last Update Posted:
    Sep 2, 2020
    Last Verified:
    Nov 1, 2019