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NCT03659136

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

Completed Phase 2 Results posted Last updated 24 February 2025
What this trial tests

Phase 2 trial testing Xentuzumab in Breast Neoplasms in 103 participants. Completed in 11 May 2022.

Timeline
28 November 2018
Primary endpoint
30 August 2021
11 May 2022

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment103
Start date28 November 2018
Primary completion30 August 2021
Estimated completion11 May 2022
Sites54 locations across France, Italy, Greece, Belgium, United Kingdom, Germany, Canada, Australia

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

18 and older, female only, with Breast Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival (PFS) Primary · From randomisation until the earliest of disease progression, death or the time point of primary PFS analysis, up to 892 days.

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.

GroupValue95% CI
1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane12.76.8 – 29.3
Placebo + 10 mg Everolimus + 25 mg Exemestane11.07.7 – 19.5
Overall Survival (OS) Secondary · From randomisation until death from any cause, up to 995 days.

Overall survival (OS) defined as the time from randomisation until death from any cause. For patients with 'event' as an outcome for OS: OS\[days\] = date of outcome - date of randomisation + 1. For patients with 'censored' as an outcome for OS: OS (censored)\[days\] = date of outcome - date of randomisation + 1.

GroupValue95% CI
1000 mg Xentuzumab + 10 mg Everolimus + 25 mg ExemestaneNA22.3 – NA
Placebo + 10 mg Everolimus + 25 mg ExemestaneNA22.3 – NA
Number of Patients With Disease Control (DC) Secondary · From randomisation until the earliest of progressive disease or death from any cause, up to 892 days.

Disease control (DC) was defined as a best overall response (BOR) of either complete response (CR), partial response (PR), stable disease (SD) or Non-CR/No-PD. SD and Non-CR/Non-PR must have been observed up until at least week 24 tumor assessment. BOR was defined according to RECIST v1.1 in combination with modified MD Anderson Criteria (for bone lesion assessment) based on all evaluable tumor assessments from randomisation until the earliest of PD, start of subsequent anti-cancer therapy, loss to follow-up, withdrawal of consent or death. To be aligned with the primary endpoint derivation, t

GroupValue95% CI
1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane29
Placebo + 10 mg Everolimus + 25 mg Exemestane25
Duration of Disease Control (DC) Secondary · From randomisation until the earliest of progressive disease or death from any cause, up to 892 days.

Duration of disease control (DC), defined as the time from randomisation until the earliest of disease progression (according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) in combination with modified MD Anderson Criteria (for bone lesion assessment) or death from any cause, among patients with DC. Duration of DC was assessed by independent reviewers. The duration of DC was calculated as followed: For patients with disease progression or death: Duration of DC \[days\] = date of outcome - date of randomisation + 1 For patients without disease progression or death: D

GroupValue95% CI
1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane14.69.2 – 29.3
Placebo + 10 mg Everolimus + 25 mg Exemestane18.49.2 – NA
Number of Participants With Objective Response (OR) Secondary · From randomisation until end of treatment, up to 892 days.

Number of participants with objective response (OR) by independent assessment. OR is defined as a best overall response of complete response (CR) or partial response (PR). Best overall response is defined according to RECIST v1.1 in combination with modified MD Anderson Criteria (for bone lesion assessment) and will consider all tumor assessments from randomisation until the earliest of PD, start of subsequent anti-cancer therapy, loss to follow-up, withdrawal of consent or death. To be aligned with the primary endpoint derivation, tumor assessments after two or more consecutively misses asses

GroupValue95% CI
1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane6
Placebo + 10 mg Everolimus + 25 mg Exemestane5
Time to Pain Progression or Intensification of Pain Palliation Secondary · 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.

Time to pain progression or intensification of pain palliation was defined as the time from randomisation until the earliest of: * 2 point increase from baseline in the Brief Pain Inventory - Short Form (BPI-SF), Item 3 (worst pain), without a decrease (of ≥1 point) from baseline analgesics use (via the 8-point Analgesic Quantification Algorithm \[AQA\]), or * 2 point increase from baseline in the AQA, or Death.

GroupValue95% CI
1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane5.63.2 – 9.3
Placebo + 10 mg Everolimus + 25 mg Exemestane3.01.9 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: [All-cause mortality]: From signing informed consent until end of study, up to 1106 days. [Serious and other adverse events]: From first drug administration until end of treatment + 42 days of residual effect period, up to 939 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane
Serious: 13/50 (26%)
Deaths: 6/52
Placebo + 10 mg Everolimus + 25 mg Exemestane
Serious: 18/51 (35%)
Deaths: 10/51

Serious adverse events (50 terms)

ReactionSystem1000 mg Xentuzumab + 10 mg…Placebo + 10 mg Everolimus…
PneumonitisRespiratory, thoracic and mediastinal disorders
AngioedemaSkin and subcutaneous tissue disorders
COVID-19 pneumoniaInfections and infestations
HyperglycaemiaMetabolism and nutrition disorders
AnaemiaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
Cardiac failureCardiac disorders
Adrenal insufficiencyEndocrine disorders
GoitreEndocrine disorders
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
NauseaGastrointestinal disorders
ProctitisGastrointestinal disorders
Salivary gland calculusGastrointestinal disorders
VomitingGastrointestinal disorders
Chest painGeneral disorders
Generalised oedemaGeneral disorders
Mucosal inflammationGeneral disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
AppendicitisInfections and infestations
COVID-19Infections and infestations
CellulitisInfections and infestations
Other adverse events (104 terms — click to expand)

ReactionSystem1000 mg Xentuzumab + 10 mg…Placebo + 10 mg Everolimus…
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
HeadacheNervous system disorders
NauseaGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
Mucosal inflammationGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
StomatitisGastrointestinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
AstheniaGeneral disorders
HyperglycaemiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
ThrombocytopeniaBlood and lymphatic system disorders
DysgeusiaNervous system disorders
PruritusSkin and subcutaneous tissue disorders
NeutropeniaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
VomitingGastrointestinal disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
Urinary tract infectionInfections and infestations
Platelet count decreasedInvestigations
Back painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
Dry mouthGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
Abdominal pain upperGastrointestinal disorders
ContusionInjury, poisoning and procedural complications
Blood creatine phosphokinase increasedInvestigations
Blood lactate dehydrogenase increasedInvestigations
Weight decreasedInvestigations
Bone painMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Pneumonitis, Angioedema, COVID-19 pneumonia, Hyperglycaemia, Anaemia, Febrile neutropenia, Atrial fibrillation, Cardiac failure.

Data from ClinicalTrials.gov NCT03659136 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy.
    Hua H, Kong Q, Yin J, Zhang J, et al · · 2020 · cited 172× · PMID 32493414 · DOI 10.1186/s13045-020-00904-3
  2. Therapeutic Targeting of the IGF Axis.
    Osher E, Macaulay VM. · · 2019 · cited 123× · PMID 31416218 · DOI 10.3390/cells8080895
  3. An Overview of Antibody Conjugated Polymeric Nanoparticles for Breast Cancer Therapy.
    Juan A, Cimas FJ, Bravo I, Pandiella A, et al · · 2020 · cited 68× · PMID 32854255 · DOI 10.3390/pharmaceutics12090802
  4. Metastasis-associated fibroblasts: an emerging target for metastatic cancer.
    Wang Z, Liu J, Huang H, Ye M, et al · · 2021 · cited 50× · PMID 34112258 · DOI 10.1186/s40364-021-00305-9
  5. The Insulin-like Growth Factor Signaling Pathway in Breast Cancer: An Elusive Therapeutic Target.
    Lee JS, Tocheny CE, Shaw LM. · · 2022 · cited 47× · PMID 36556357 · DOI 10.3390/life12121992
  6. Disrupting Insulin and IGF Receptor Function in Cancer.
    Cao J, Yee D. · · 2021 · cited 38× · PMID 33429867 · DOI 10.3390/ijms22020555
  7. Role of the IGF-1 Axis in Overcoming Resistance in Breast Cancer.
    Ianza A, Sirico M, Bernocchi O, Generali D. · · 2021 · cited 32× · PMID 33829018 · DOI 10.3389/fcell.2021.641449
  8. Growth Hormone/Insulin Growth Factor Axis in Sex Steroid Associated Disorders and Related Cancers.
    Bleach R, Sherlock M, O'Reilly MW, McIlroy M. · · 2021 · cited 27× · PMID 33816477 · DOI 10.3389/fcell.2021.630503

Verify or expand the search:

Other trials of Xentuzumab

Trials testing the same drug.

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Other Boehringer Ingelheim trials

Trials by the same sponsor.

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