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

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.)

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Placebo; Drug: Seribantumab; Drug: Fulvestrant

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 Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • LKH - Universitätsklinikum Graz
  • Innsbruck, Austria, 6020
    • Universitaetsklinik fuer Gynaekologie und Geburtshilfe
  • Linz, Austria, 4010
    • Krankenhaus der Barmherzigen Schwestern Linz
  • Vienna, Austria, 1090
    • Medizinische Universität Wien
  • Wien, Austria, 1090
    • Medizinische Universität Wien
• Belgium
  • Antwerp, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Namur, Belgium, 5000
    • CHU UCL NAMUR - Sainte Elisabeth
  • Brabant Wallon
    • Ottignies, Brabant Wallon, Belgium, 1340
      • Clinique Saint-Pierre
  • Luxembourg
    • Libramont, Luxembourg, Belgium, 6800
      • Centre Hospitalier de l'Ardenne - Clinique du Sein
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • Universitaire Ziekenhuis Leuven
• Canada
  • Montreal, Canada, H3T 1E2
    • McGill University - Jewish General Hospital
  • Quebec, Canada, G1S 4L8
    • Centre hospitalier affilié universitaire de Québec
  • Alberta
    • Calgary, Alberta, Canada, T2S 3C3
      • University of Calgary
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • British Columbia Cancer Agency
• Germany
  • Bonn, Germany, 53111
    • Medizinisches Zentrum Bonn Friedensplatz
  • Frankfurt, Germany
    • Centrum fuer Haematologie und Onkologie Bethanien
  • Hannover, Germany, 30177
    • Gynakologisch-Onkologische Praxis Hannover
  • Munich, Germany, 80637
    • Rotkreuzklinikum München-Frauenklinik
  • München, Germany, 81675
    • Klinikum rechts der Isar der Technischen Universitat Munchen
  • Troisdorf, Germany, 53840
    • Onkologie Rheinsieg
  • Ulm, Germany, 89075
    • Universitätsklinikum Ulm
  • Bayern
    • Erlangen, Bayern, Germany, 91054
      • Universitätsklinikum Erlangen
• Spain
  • A Coruña, Spain, 15006
    • Hospital Teresa Herrera
  • Gerona, Spain, 17007
    • Hospital Universitari de Girona Doctor Josep Trueta
  • Jaén, Spain, 23007
    • Complejo Hospitalario de Jaén
  • La Coruña, Spain, 15006
    • Complejo Hospitalario Universitario La Coruna
  • Lleida, Spain, 25198
    • Hospital Universitari Arnau de Vilanova
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28040
    • Hospital Clínico San Carlos
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de La Victoria
  • Palma de Mallorca, Spain, 07198
    • Hospital Son Llatzer
  • Sevilla, Spain, 41009
    • De La Cruz Merino, Luis
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
  • Zaragoza, Spain, 59009
    • Hospital Universitario Miguel Servet
  • Barcelona
    • Sant Cugat Del Vallès, Barcelona, Spain, 08190
      • Hospital Universitari General de Catalunya
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer and Research Centers- Chandler
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highland Oncology Group
  • California
    • Beverly Hills, California, United States, 90404-2131
      • Beverly Hills Cancer Center
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Saint Helena, California, United States, 94574
      • Saint Helena Hospital
  • Connecticut
    • Stamford, Connecticut, United States, 06902-3628
      • Stamford Hospital
  • Florida
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center
    • Orlando, Florida, United States, 32806
      • UF Health Cancer Center at Orlando Health
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Columbus Regional Research Institute
  • Illinois
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Central Illinois
  • Maryland
    • Frederick, Maryland, United States, 21701
      • James M Stockman Cancer Institute
    • Silver Spring, Maryland, United States, 20902
      • Holy Cross Hospital Health Center
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinical Medical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi
  • Missouri
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Saint Francis Cancer Treatment Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Lineberger Comprehensive Cancer Center
    • Charlotte, North Carolina, United States, 28207
      • Oncology Specialists of Charlotte
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah Health Care - Huntsman Cancer institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	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.	Randomization until death due to any cause up to 13 months (The study terminated prematurely)
Objective Response Rate	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.	Randomization through end of study up to 13 months (The study terminated prematurely)
Time to Progression	Time to Progression (TTP) is defined as the time from the date of randomization to the date of objective tumor progression.	Randomization to date of objective tumor progression up to 13 months (The study terminated prematurely)
Number of Participants With Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone	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.	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
Percentage of Treatment-emergent Adverse Events Reported With the Combinations of Seribantumab Plus Fulvestrant Versus Fulvestrant Alone	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.	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
Pharmacokinetic (PK) Profile of Seribantumab When Given in Combination With Fulvestrant and of Fulvestrant When Given in Combination With Serbantumab.	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).	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

Collaborators and Investigators

• Sponsor: Elevation Oncology
• Investigators: Study Director: Marc Pipas, MD, Merrimack Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 15, 2017
• Primary Completion (ACTUAL): November 30, 2018
• Study Completion (ACTUAL): November 30, 2018

Study Registration Dates

• First Submitted: August 2, 2017
• First Submitted That Met QC Criteria: August 7, 2017
• First Posted (ACTUAL): August 8, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 2, 2020
• Last Update Submitted That Met QC Criteria: August 20, 2020
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Breast Cancer, HER2 Negative, Hormone receptor positive
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant
• Other Study ID Numbers: MM-121-02-02-10; 2017-000565-76 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No