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    DRUG:

    xentuzumab (BI-836845)

    i
    Other names: BI-836845, BI836845, BI 836845
    Company:
    Boehringer Ingelheim, Novartis
    Drug class:
    IGF-2 inhibitor, IGF1 inhibitor
    5ms
    This Study in Patients With Different Types of Cancer (Solid Tumours) Aims to Find a Safe Dose of Xentuzumab in Combination With Abemaciclib With or Without Hormonal Therapies. The Study Also Tests How Effective These Medicines Are in Patients With Lung and Breast Cancer (clinicaltrials.gov)
    P1, N=133, Completed, Boehringer Ingelheim | Active, not recruiting --> Completed
    Trial completion • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor)
    |
    Verzenio (abemaciclib) • fulvestrant • letrozole • anastrozole • xentuzumab (BI-836845)
    11ms
    This Study in Patients With Different Types of Cancer (Solid Tumours) Aims to Find a Safe Dose of Xentuzumab in Combination With Abemaciclib With or Without Hormonal Therapies. The Study Also Tests How Effective These Medicines Are in Patients With Lung and Breast Cancer. (clinicaltrials.gov)
    P1, N=133, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Dec 2023 --> Apr 2024
    Trial completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor)
    |
    EGFR mutation • HER-2 negative • ALK translocation
    |
    Verzenio (abemaciclib) • fulvestrant • letrozole • anastrozole • xentuzumab (BI-836845)
    1year
    A Phase Ib/II study of IGF-neutralising antibody xentuzumab with enzalutamide in metastatic castration-resistant prostate cancer. (PubMed, Br J Cancer)
    Xentuzumab plus enzalutamide was tolerable but lacked antitumour activity in unselected patients with mCRPC.
    P1/2 data • Clinical Trial,Phase II • Journal • Metastases
    |
    PTEN (Phosphatase and tensin homolog) • IGF1 (Insulin-like growth factor 1)
    |
    docetaxel • Xtandi (enzalutamide capsule) • abiraterone acetate • xentuzumab (BI-836845)
    over1year
    This Study in Patients With Different Types of Cancer (Solid Tumours) Aims to Find a Safe Dose of Xentuzumab in Combination With Abemaciclib With or Without Hormonal Therapies. The Study Also Tests How Effective These Medicines Are in Patients With Lung and Breast Cancer. (clinicaltrials.gov)
    P1, N=133, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Aug 2023 --> Dec 2023
    Trial completion date • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor)
    |
    EGFR mutation • HER-2 negative • ALK translocation
    |
    Verzenio (abemaciclib) • fulvestrant • letrozole • anastrozole • xentuzumab (BI-836845)
    over1year
    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. (PubMed, Breast Cancer Res)
    While this study demonstrated that xentuzumab could be safely combined with everolimus and exemestane in patients with HR-positive/HER2-negative advanced breast cancer with non-visceral disease, there was no PFS benefit with the addition of xentuzumab. Trial registration ClinicalTrials.gov, NCT03659136. Prospectively registered, September 6, 2018.
    P2 data • Journal • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • IGF1 (Insulin-like growth factor 1) • IGF2 (Insulin-like growth factor 2)
    |
    HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative
    |
    everolimus • exemestane • xentuzumab (BI-836845)
    over1year
    Identification of IGF2 as Genomic Driver and Actionable Therapeutic Target in Hepatoblastoma. (PubMed, Mol Cancer Ther)
    The antitumor effect of xentuzumab (a monoclonal antibody targeting IGF1/2) alone or in combination with the conventional therapeutic agent cisplatin was assessed in HB cell lines, in PDX-derived HB organoids and in a xenograft HB murine model. These results suggest that IGF2 is an HB actionable driver and that, in preclinical models of HB, the combination of IGF1/2 inhibition with cisplatin induces superior antitumor effects than cisplatin monotherapy. Overall, our study provides a rationale for testing IGF2 inhibitors in combination with cisplatin in HB patients with IGF2 overexpression.
    Journal
    |
    IGF1 (Insulin-like growth factor 1) • IGF2 (Insulin-like growth factor 2) • MIR483 (MicroRNA 483)
    |
    IGF2 overexpression
    |
    cisplatin • xentuzumab (BI-836845)
    over2years
    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 (clinicaltrials.gov)
    P2, N=103, Completed, Boehringer Ingelheim | Active, not recruiting --> Completed
    Trial completion • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor)
    |
    HER-2 negative • PGR positive
    |
    everolimus • exemestane • xentuzumab (BI-836845)
    almost3years
    BI 836845 in Estrogen Receptor Positive Metastatic Breast Cancer (clinicaltrials.gov)
    P1, N=164, Completed, Boehringer Ingelheim | Active, not recruiting --> Completed
    Trial completion • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
    |
    everolimus • exemestane • xentuzumab (BI-836845)
    almost3years
    A phase 1 trial of xentuzumab, an IGF-neutralizing antibody, in Japanese patients with advanced solid tumors. (PubMed, Cancer Sci)
    Xentuzumab monotherapy was well tolerated in Japanese patients and showed evidence of anti-tumor activity. This study was registered with www.clinicaltrials.gov (NCT02145741).
    Clinical • P1 data • Journal
    |
    IGF1 (Insulin-like growth factor 1) • IGF2 (Insulin-like growth factor 2)
    |
    xentuzumab (BI-836845)
    almost3years
    CHK1 inhibition exacerbates replication stress induced by IGF blockade. (PubMed, Oncogene)
    Aiming to exploit this effect in therapy we performed a compound screen in five breast cancer cell lines with IGF neutralising antibody xentuzumab...Exogenous RRM2 expression rescued hallmarks of replication stress induced by co-inhibiting IGF with CHK1 or WEE1, identifying RRM2 as a critical target of the functional IGF:CHK1 and IGF:WEE1 interactions. These data identify novel therapeutic vulnerabilities and may inform future trials of IGF inhibitory drugs.
    Journal
    |
    RRM2 (Ribonucleotide Reductase Regulatory Subunit M2)
    |
    xentuzumab (BI-836845)
    3years
    Xentuzumab plus abemaciclib and fulvestrant in patients (pts) with hormone receptor-positive (HR+), HER2-negative advanced breast cancer (aBC) with visceral or non-visceral disease: First report of progression-free survival (PFS) results from a phase Ib study (SABCS 2021)
    No abstract available
    Clinical • P1 data
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HR positive • HER-2 negative
    |
    Verzenio (abemaciclib) • fulvestrant • xentuzumab (BI-836845)
    3years
    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 (clinicaltrials.gov)
    P2, N=103, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Nov 2022 --> Mar 2022 | Trial primary completion date: Dec 2021 --> Aug 2021
    Clinical • Trial completion date • Trial primary completion date • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor)
    |
    HER-2 negative • PGR positive
    |
    everolimus • exemestane • xentuzumab (BI-836845)
    3years
    This Study in Patients With Different Types of Cancer (Solid Tumours) Aims to Find a Safe Dose of Xentuzumab in Combination With Abemaciclib With or Without Hormonal Therapies. The Study Also Tests How Effective These Medicines Are in Patients With Lung and Breast Cancer. (clinicaltrials.gov)
    P1, N=133, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting
    Clinical • Enrollment closed • Combination therapy
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor)
    |
    EGFR mutation • HER-2 negative • ALK translocation
    |
    Verzenio (abemaciclib) • fulvestrant • letrozole • anastrozole • xentuzumab (BI-836845)
    3years
    Phase 1b Open-Label Trial of Afatinib Plus Xentuzumab (BI 836845) in Patients With EGFR Mutation-Positive NSCLC After Progression on EGFR Tyrosine Kinase Inhibitors. (PubMed, JTO Clin Res Rep)
    The most common drug-related adverse events were diarrhea (75 %), paronychia (69 %), and rash (69 %) in part A and diarrhea (31 %), rash (19 %), paronychia (19 %), and fatigue (19 %) in part B. There were no new safety issues; xentuzumab and afatinib could be safely coadministered. Nevertheless, the combination revealed only modest activity in patients with EGFR mutation-positive, T790M-negative NSCLC after progression on afatinib.
    Clinical • P1 data • Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR T790M • EGFR T790M negative
    |
    Gilotrif (afatinib) • xentuzumab (BI-836845)
    over3years
    BI 836845 in Estrogen Receptor Positive Metastatic Breast Cancer (clinicaltrials.gov)
    P1, N=164, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Jul 2021 --> Jan 2022
    Clinical • Trial completion date • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
    |
    everolimus • exemestane • xentuzumab (BI-836845)
    over3years
    This Study in Patients With Different Types of Cancer (Solid Tumours) Aims to Find a Safe Dose of Xentuzumab in Combination With Abemaciclib With or Without Hormonal Therapies. The Study Also Tests How Effective These Medicines Are in Patients With Lung and Breast Cancer. (clinicaltrials.gov)
    P1, N=148, Recruiting, Boehringer Ingelheim | Trial completion date: Apr 2023 --> Jul 2023 | Trial primary completion date: Nov 2022 --> Feb 2023
    Clinical • Trial completion date • Trial primary completion date • Combination therapy
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor)
    |
    EGFR mutation • HER-2 negative • ALK translocation
    |
    Verzenio (abemaciclib) • fulvestrant • letrozole • anastrozole • xentuzumab (BI-836845)
    over3years
    [VIRTUAL] A phase Ib study of xentuzumab plus abemaciclib and fulvestrant in patients (pts) with advanced hormone receptor-positive (HR+), HER2-negative breast cancer (BC) with visceral or non-visceral disease. (ASCO 2021)
    Combining xentuzumab, an insulin-like growth factor (IGF) ligand-neutralizing antibody, with ET and everolimus, suggested progression-free survival (PFS) benefit in pts with advanced HR+ BC and non-visceral disease . Xentuzumab plus abemaciclib and fulvestrant demonstrated encouraging disease control in pts with advanced HR+ BC with visceral and non-visceral disease . The safety profile was manageable, and consistent with the known profiles of the three agents.
    Clinical • P1 data
    |
    HER-2 (Human epidermal growth factor receptor 2) • CCND1 (Cyclin D1)
    |
    HR positive • HER-2 negative
    |
    everolimus • Verzenio (abemaciclib) • fulvestrant • xentuzumab (BI-836845)
    over3years
    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 (clinicaltrials.gov)
    P2, N=100, Recruiting, Boehringer Ingelheim | Active, not recruiting --> Recruiting
    Clinical • Enrollment open • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor)
    |
    HER-2 negative • PGR positive
    |
    everolimus • exemestane • xentuzumab (BI-836845)
    over3years
    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 (clinicaltrials.gov)
    P2, N=103, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting
    Clinical • Enrollment closed • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor)
    |
    HER-2 negative • PGR positive
    |
    everolimus • exemestane • xentuzumab (BI-836845)
    almost4years
    This Study in Patients With Different Types of Cancer (Solid Tumours) Aims to Find a Safe Dose of Xentuzumab in Combination With Abemaciclib With or Without Hormonal Therapies. The Study Also Tests How Effective These Medicines Are in Patients With Lung and Breast Cancer. (clinicaltrials.gov)
    P1, N=148, Recruiting, Boehringer Ingelheim | Trial completion date: Jan 2023 --> Apr 2023 | Trial primary completion date: Aug 2022 --> Nov 2022
    Clinical • Trial completion date • Trial primary completion date • Combination therapy
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor)
    |
    EGFR mutation • HER-2 negative • ALK translocation
    |
    Verzenio (abemaciclib) • fulvestrant • letrozole • anastrozole • xentuzumab (BI-836845)
    almost4years
    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. (PubMed, Breast Cancer Res)
    Addition of xentuzumab to everolimus/exemestane did not improve PFS in the overall population, leading to early discontinuation of the trial. Evidence of PFS benefit was observed in patients without visceral metastases when treated with xentuzumab/everolimus/exemestane, leading to initiation of the phase II XENERA™-1 trial (NCT03659136).
    P1/2 data • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • IGF1 (Insulin-like growth factor 1) • IGF2 (Insulin-like growth factor 2)
    |
    HER-2 positive • HR positive • HER-2 negative • HR positive + HER-2 negative
    |
    everolimus • exemestane • xentuzumab (BI-836845)
    almost4years
    Two first-in-human studies of xentuzumab, a humanised insulin-like growth factor (IGF)-neutralising antibody, in patients with advanced solid tumours. (PubMed, Br J Cancer)
    Xentuzumab was well tolerated; MTD was not reached. RBD was 1000 mg weekly, confirmed by BLRM. Xentuzumab showed preliminary anti-tumour activity.
    Clinical • P1 data • Journal
    |
    IGF1 (Insulin-like growth factor 1) • IGF2 (Insulin-like growth factor 2)
    |
    xentuzumab (BI-836845)
    almost4years
    BI 836845 in Estrogen Receptor Positive Metastatic Breast Cancer (clinicaltrials.gov)
    P1, N=164, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Nov 2020 --> Jul 2021
    Clinical • Trial completion date • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
    |
    everolimus • exemestane • xentuzumab (BI-836845)
    over4years
    This Study in Patients With Different Types of Cancer (Solid Tumours) Aims to Find a Safe Dose of Xentuzumab in Combination With Abemaciclib With or Without Hormonal Therapies. The Study Also Tests How Effective These Medicines Are in Patients With Lung and Breast Cancer. (clinicaltrials.gov)
    P1, N=148, Recruiting, Boehringer Ingelheim | Trial completion date: Jun 2022 --> Jan 2023 | Trial primary completion date: Jan 2022 --> Aug 2022
    Clinical • Trial completion date • Trial primary completion date • Combination therapy
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor)
    |
    EGFR mutation • HER-2 negative • ALK translocation
    |
    Verzenio (abemaciclib) • fulvestrant • letrozole • anastrozole • xentuzumab (BI-836845)
    over4years
    [VIRTUAL] An open label, multi-cohort, phase Ib study of xentuzumab and abemaciclib: Preliminary results from the advanced non-small cell lung cancer (NSCLC) cohort (AACR-II 2020)
    The combination of xentuzumab and abemaciclib showed preliminary efficacy in pts with NSCLC who had progressed on chemotherapy and an immune checkpoint inhibitor. One PR was reported. The combination had a manageable safety profile.
    Clinical • P1 data
    |
    CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4)
    |
    Verzenio (abemaciclib) • xentuzumab (BI-836845)
    over4years
    [VIRTUAL] Xentuzumab, a humanized IGF-1 and IGF-2 ligand co-neutralizing monoclonal antibody, shows efficacy in a human breast cancer model of bone metastasis (AACR-II 2020)
    In summary, the IGF-1/-2 neutralizing antibody xentuzumab showed efficacy in a breast cancer bone metastasis model (with and without everolimus) but did not affect metastatic tumor growth in lung/visceral organs. A phase II trial evaluating the xentuzumab/ everolimus/ exemestane triple combination in HR+BC patients with non-visceral disease is currently ongoing (NCT03659136).
    Clinical • Preclinical
    |
    IGF1R (Insulin-like growth factor 1 receptor) • IGF1 (Insulin-like growth factor 1) • IGF2 (Insulin-like growth factor 2) • IR (Insulin receptor)
    |
    everolimus • xentuzumab (BI-836845)
    over4years
    This Study in Patients With Different Types of Cancer (Solid Tumours) Aims to Find a Safe Dose of Xentuzumab in Combination With Abemaciclib With or Without Hormonal Therapies. The Study Also Tests How Effective These Medicines Are in Patients With Lung and Breast Cancer. (clinicaltrials.gov)
    P1, N=148, Recruiting, Boehringer Ingelheim | Suspended --> Recruiting
    Clinical • Enrollment open • Combination therapy
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor)
    |
    EGFR mutation • HER-2 negative • ALK translocation
    |
    Verzenio (abemaciclib) • fulvestrant • letrozole • anastrozole • xentuzumab (BI-836845)
    over4years
    [VIRTUAL] Xentuzumab (Xe) in combination with everolimus (Ev) and exemestane (Ex) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) and non-visceral involvement (XENERA™-1) (ESMO-BC-I 2020)
    Funding: Boehringer Ingelheim. Clinical trial identification: 2017-003131-11/NCT03659136.
    Clinical • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • IGF1 (Insulin-like growth factor 1)
    |
    HR positive • HER-2 negative • HR positive + HER-2 negative
    |
    everolimus • exemestane • xentuzumab (BI-836845)
    over4years
    [VIRTUAL] Xentuzumab (Xe) in combination with everolimus (Ev) and exemestane (Ex) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) and non-visceral involvement (XENERA™-1) (ESMO-BC-I 2020)
    Funding: Boehringer Ingelheim. Clinical trial identification: 2017-003131-11/NCT03659136.
    Clinical • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • IGF1 (Insulin-like growth factor 1)
    |
    HR positive • HER-2 negative • HR positive + HER-2 negative
    |
    everolimus • exemestane • xentuzumab (BI-836845)
    over4years
    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 (clinicaltrials.gov)
    P2, N=80, Suspended, Boehringer Ingelheim | Recruiting --> Suspended
    Clinical • Trial suspension • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor)
    |
    HER-2 negative • PGR positive
    |
    everolimus • exemestane • xentuzumab (BI-836845)
    over4years
    Xentuzumab (Xe) in combination with everolimus (Ev) and exemestane (Ex) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) and non-visceral involvement (XENERA™-1) (ESMO-BC 2020)
    No abstract available
    Clinical • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    everolimus • xentuzumab (BI-836845)
    over4years
    Anti-Tumor Activity of the IGF-1/IGF-2-Neutralizing Antibody Xentuzumab (BI 836845) in Combination with Enzalutamide in Prostate Cancer Models. (PubMed, Mol Cancer Ther)
    The data suggest that XENT+ENZA combination therapy may overcome castration resistance and could be effective in patients who are resistant to ENZA alone. PTEN status as a biomarker of responsiveness to combination therapy needs further investigation.
    Preclinical • Journal • Combination therapy
    |
    PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • IGF1R (Insulin-like growth factor 1 receptor) • IGF1 (Insulin-like growth factor 1) • IGF2 (Insulin-like growth factor 2)
    |
    Xtandi (enzalutamide capsule) • xentuzumab (BI-836845)
    almost5years
    BI 836845 in Estrogen Receptor Positive Metastatic Breast Cancer (clinicaltrials.gov)
    P1, N=164, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Jan 2020 --> Sep 2020
    Clinical • Trial completion date • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
    |
    everolimus • exemestane • xentuzumab (BI-836845)
    5years
    A phase Ib multi-cohort study of xentuzumab and abemaciclib in patients (pts) with solid tumors and breast cancer (BC) - initial report of four dose-finding cohorts (SABCS 2019)
    One of 3 ETs was combined with xentuzumab plus abemaciclib (doses determined in Part 1): Cohort B, letrozole; Cohort C, anastrozole; Cohort D, fulvestrant. The MTD and RP2D of xentuzumab was 1000 mg i.v. weekly plus abemaciclib 150 mg p.o. Q12h with or without ET. The safety profile of xentuzumab in combination with abemaciclib, with or without ET, was tolerable and manageable, with no new safety signals. Expansion cohorts for xentuzumab plus abemaciclib and fulvestrant in HR+ HER2- BC are ongoing.
    Clinical • P1 data
    |
    HER-2 (Human epidermal growth factor receptor 2) • CDK4 (Cyclin-dependent kinase 4) • IGF1R (Insulin-like growth factor 1 receptor) • IGF1 (Insulin-like growth factor 1)
    |
    Verzenio (abemaciclib) • fulvestrant • letrozole • anastrozole • xentuzumab (BI-836845)