SHERBOC: Phase 2 Trial of Seribantumab Plus Fulvestrant in Postmenopausal Women With Metastatic Breast Cancer
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
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:
Drug: Fulvestrant
Fulvestrant is an estrogen receptor antagonist with no agonist effects
Other Names:
|
Active Comparator: Arm B Placebo Fulvestrant |
Drug: Fulvestrant
Fulvestrant is an estrogen receptor antagonist with no agonist effects
Other Names:
Drug: Placebo
Placebo
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
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.
-
Patients must have histologically or cytologically confirmed ER+ and/or PR+ (with staining of >1% cells) breast cancer.
-
Patients with confirmed postmenopausal status due to either surgical/natural menopause or ovarian suppression.
-
Patients must be HER2 negative.
-
Patient must have at least one lesion amenable to either core needle biopsy or fine needle aspiration.
-
Patient must have a positive in-situ hybridization (ISH) test for heregulin, as determined by centralized testing of unstained tumor tissue.
-
Patients that have progressed following at least one but no more than two prior systemic therapies in the locally advanced or metastatic disease setting.
-
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).
-
Patients with bone-only lesions who have received radiation to those lesions must have documented progression following radiation therapy.
-
ECOG Performance Score (PS) of 0 or 1.
-
Patients with adequate bone marrow reserves.
-
Adequate hepatic function.
-
Adequate renal function.
-
Patient has recovered from clinically significant effects of any prior, surgery, radiosurgery, or other antineoplastic therapy.
-
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.
-
Prior treatment with an anti-ErbB3 antibody.
-
Prior treatment with a chemotherapy in the locally advanced or metastatic disease setting.
-
Patients cannot have received prior treatment with fulvestrant or other SERDs in the locally advanced or metastatic setting.
-
Uncontrolled CNS disease or presence of leptomeningeal disease.
-
Inflammatory breast cancer.
-
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.
-
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.
-
Known hypersensitivity to any of the components of seribantumab, fulvestrant, or who have had hypersensitivity reactions to fully human monoclonal antibodies.
-
NYHA Class III or IV congestive heart failure.
-
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.
-
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.- MM-121-02-02-10
- 2017-000565-76
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
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%
|
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%
|
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 |
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
|
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%
|
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
|
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
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 |
clinical@elevationoncology.com |
- MM-121-02-02-10
- 2017-000565-76