The XENERA™ 1 Study Tests Xentuzumab in Combination With Everolimus and Exemestane in Women With Hormone Receptor Positive and HER2-negative Breast Cancer That Has Spread

NCT03659136 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 1280-00222017-003131-11
• Study Type: interventional
• Target: 103
• Locations: 11 countries
• Sites: 54

Brief Summary

The main objective of the trial is to assess the efficacy of xentuzumab in combination with everolimus and exemestane over everolimus and exemestane in patients with HR+/ HER2- advanced or metastatic breast cancer and non-visceral disease.

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Progression-free survival (PFS) defined as the time from randomisation until progressive disease (PD) according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) in combination with modified MD Anderson Criteria (for bone lesion assessment), based on blinded independent assessment or death from any cause, whichever occurred earlier. As per RECIST, PD is defined as at least a 20% increase in the sum of diameters of target lesions, unequivocal progression of non-target lesions or the appearance of new lesions.

  From randomisation until the earliest of disease progression, death or the time point of primary PFS analysis, up to 892 days.

Secondary Outcomes (5)

• Overall Survival (OS)

  From randomisation until death from any cause, up to 995 days.

• Number of Patients With Disease Control (DC)

  From randomisation until the earliest of progressive disease or death from any cause, up to 892 days.

• Duration of Disease Control (DC)

  From randomisation until the earliest of progressive disease or death from any cause, up to 892 days.

• Number of Participants With Objective Response (OR)

  From randomisation until end of treatment, up to 892 days.

• Time to Pain Progression or Intensification of Pain Palliation

  From randomisation until the earliest of pain progression, intensification of pain palliation, death or the time point of progression free survival analysis, up to 843 days.

Study Arms (2)

Xentuzumab/everolimus/exemestane

EXPERIMENTAL

Drug: Xentuzumab; Drug: Everolimus; Drug: Exemestane

Placebo/everolimus/exemestane

PLACEBO COMPARATOR

Drug: Placebo; Drug: Everolimus; Drug: Exemestane

Interventions

Xentuzumab DRUG

Intravenous infusion

Xentuzumab/everolimus/exemestane

Placebo DRUG

Intravenous infusion

Placebo/everolimus/exemestane

Everolimus DRUG

Tablet

Placebo/everolimus/exemestane; Xentuzumab/everolimus/exemestane

Exemestane DRUG

Tablet

Placebo/everolimus/exemestane; Xentuzumab/everolimus/exemestane

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented histologically confirmed breast cancer with ERand/ or PgR-positive and HER2-negative status
• Locally advanced or metastatic breast cancer not deemed amenable to curative surgery or curative radiation therapy
• Archival tumour sample available at the time of informed consent and provided to the central laboratory around the time of randomisation. Patients must provide a formalin-fixed paraffin embedded (FFPE) tissue biopsy sample preferably taken at the time of presentation with recurrent or metastatic disease (provision of a biopsy sample taken from the bone is not acceptable).
• Patients must satisfy the following criteria for prior therapy:
• Disease progression during treatment or within 12 months of completion of endocrine adjuvant therapy or
• Disease progression while on or within 1 month after the end of prior endocrine therapy for advanced/metastatic breast cancer (Note: the endocrine therapy does not have to be the treatment immediately prior to trial entry).
• Patients must have
• At least one measurable non-visceral lesion according to RECIST version 1.1 in either lymph nodes, soft tissue, skin and/or
• At least one measurable non-visceral lesion according to RECIST version 1.1 as lytic or mixed (lytic + blastic) in bone and/or
• At least one non-measurable (lytic, mixed lytic + blastic, or blastic) bone lesion according to RECIST version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
• Fasting glucose \<8.9 mmol/L (\<160 mg/dL) and HbA1c \<8.0%
• Adequate organ function

You may not qualify if:

• Previous treatment with agents targeting the IGF pathway, AKT, or mTOR pathways
• Prior treatment with exemestane (except adjuvant exemestane stopped \>12 months prior to start of study treatment as long as the patient did not recur during or within 12 months after the end of adjuvant exemestane)
• Evidence of visceral metastasis/es (i.e. liver, lung, peritoneal, pleural metastases, malignant pleural effusions, malignant peritoneal effusions) at screening. NOTE: Patients with a past history of visceral metastases are eligible if visceral metastases have completely resolved at least 3 months
• History or evidence of metastatic disease to the brain
• Leptomeningeal carcinomatosis
• More than 1 prior line of chemotherapy for HR+ HER2- metastatic breast cancer
• Radiotherapy within 4 weeks prior to the start of study treatment
• Use of concomitant systemic sex hormone therapy
• History or presence of cardiovascular abnormalities
• Known pre-existing interstitial lung disease

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (54)

Ironwood Cancer and Research Centers

Chandler, Arizona, 85224, United States

Location

Cancer Treatment Centers of America at Western Regional Medical Center

Goodyear, Arizona, 85338, United States

Location

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

Location

University of California San Francisco

San Francisco, California, 94158, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

University Cancer and Blood Center

Athens, Georgia, 30607, United States

Location

Hematology Oncology of Indiana

Indianapolis, Indiana, 46260, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

HCA MidAmerica Division, Inc.

Kansas City, Missouri, 64132, United States

Location

Hematology Oncology Associates of Rockland

Nyack, New York, 10960, United States

Location

Southwestern Regional Medical Center

Tulsa, Oklahoma, 74133, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

The Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

Utah Cancer Specialists Cancer Center

Salt Lake City, Utah, 84106, United States

Location

Northwest Medical Specialties, PLLC

Tacoma, Washington, 98405, United States

Location

The Tweed Hospital

Tweed Heads, New South Wales, 2485, Australia

Location

Peninsula Haematology & Oncology

Frankston, Victoria, 3199, Australia

Location

Brussels - UNIV Saint-Luc

Brussels, 1200, Belgium

Location

Brussels - UNIV UZ Brussel

Jette, 1090, Belgium

Location

Kortrijk - HOSP AZ Groeninge Kennedylaan

Kortrijk, 8500, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

CHU de Quebec-Universite Laval Research Centre

Québec, G1S 4L8, Canada

Location

INS Sainte Catherine

Avignon, 84000, France

Location

HOP Victor Hugo

Le Mans, 72000, France

Location

INS Paoli-Calmettes

Marseille, 13009, France

Location

INS Curie

Paris, 75248, France

Location

HOP Européen G. Pompidou

Paris, 75908, France

Location

HOP Lyon Sud

Pierre-Bénite, 69495, France

Location

INS Claudius Regaud IUCT-Oncopole

Toulouse, 31059, France

Location

Universitätsklinikum Erlangen

Erlangen, 91054, Germany

Location

Vincentius-Diakonissen-Kliniken gAG

Karlsruhe, 76135, Germany

Location

General Hospital of Athens "Alexandra"

Athens, 11528, Greece

Location

University General Hospital of Heraklion

Heraklion, 71110, Greece

Location

University Hospital of Larisa, Oncology Clinic

Larissa, 41334, Greece

Location

Metropolitan Hospital, Oncology Clinic

Neo Faliro, Athens, 18547, Greece

Location

Euromedica Kyanous Stavros General Hospital

Thessaloniki, 54645, Greece

Location

Istituto Nazionale IRCCS Tumori Fondazione Pascale

Napoli, 80131, Italy

Location

Iov, Irccs

Padua, 35128, Italy

Location

Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza

Roma, 00189, Italy

Location

Fundação Champalimaud,

Lisbon, 1400-038, Portugal

Location

Hospital Beatriz Ângelo

Loures, 2674-514, Portugal

Location

Centro Hospitalar de Vila Nova de Gaia

Vila Nova de Gaia, 4434-502, Portugal

Location

Hospital Teresa Herrera

A Coruña, 15006, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Arnau de Vilanova

Lleida, 25198, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, 29010, Spain

Location

Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Clínica Quirón de Valencia

Valencia, 46010, Spain

Location

Hospital Clínico de Valencia

Valencia, 46010, Spain

Location

St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

Related Publications (2)

• Schmid P, Cortes J, Joaquim A, Janez NM, Morales S, Diaz-Redondo T, Blau S, Neven P, Lemieux J, Garcia-Saenz JA, Hart L, Biyukov T, Baktash N, Massey D, Burris HA 3rd, Rugo HS. XENERA-1: a randomised double-blind Phase II trial of xentuzumab in combination with everolimus and exemestane versus everolimus and exemestane in patients with hormone receptor-positive/HER2-negative metastatic breast cancer and non-visceral disease. Breast Cancer Res. 2023 Jun 12;25(1):67. doi: 10.1186/s13058-023-01649-w.

  PMID: 37308971 DERIVED

• Schmid P, Sablin MP, Bergh J, Im SA, Lu YS, Martinez N, Neven P, Lee KS, Morales S, Perez-Fidalgo JA, Adamson D, Goncalves A, Prat A, Jerusalem G, Schlieker L, Espadero RM, Bogenrieder T, Huang DC, Crown J, Cortes J. A phase Ib/II study of xentuzumab, an IGF-neutralising antibody, combined with exemestane and everolimus in hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer. Breast Cancer Res. 2021 Jan 15;23(1):8. doi: 10.1186/s13058-020-01382-8.

  PMID: 33451345 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Breast Neoplasms

Interventions

xentuzumab; Everolimus; exemestane

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Boehringer Ingelheim
• Organization: Boehringer Ingelheim, Call Centre

clintriage.rdg@boehringer-ingelheim.com

018002430127

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2018
• First Posted: September 6, 2018
• Study Start: November 28, 2018
• Primary Completion: August 30, 2021
• Study Completion: May 11, 2022
• Last Updated: February 24, 2025
• Results First Posted: September 29, 2022

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (16); GB (1); IT (3); GR (5); FR (7); AU (2); DE (2); BE (4); PT (3); ES (10); CA (1)