xentuzumab (BI-836845) / Boehringer Ingelheim, Novartis - LARVOL DELTA

WINGMEN: IGF Inhibition With Xentuzumab Prior to Radical Prostatectomy (clinicaltrials.gov) - P1 | N=27 | Completed | Sponsor: University of Oxford | Active, not recruiting ➔ Completed

Trial completion • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

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 | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Trial completion • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ER • HER-2 • PGR

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 | Sponsor: Boehringer Ingelheim | Trial completion date: Dec 2023 ➔ Apr 2024

Combination therapy • Metastases • Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ER • HER-2 • PGR

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 | Sponsor: Boehringer Ingelheim | Trial completion date: Aug 2023 ➔ Dec 2023

Combination therapy • Metastases • Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ER • HER-2 • PGR

A Phase Ib/II study of IGF-neutralising antibody xentuzumab with enzalutamide in metastatic castration-resistant prostate cancer. (PubMed, Br J Cancer) - P1 | "Xentuzumab plus enzalutamide was tolerable but lacked antitumour activity in unselected patients with mCRPC."

Journal • Metastases • P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • IGF1 • PTEN

A Phase Ib/II study of IGF-neutralising antibody xentuzumab with enzalutamide in metastatic castration-resistant prostate cancer (Nature, Br J Cancer) - P1b/2 | N=120 | NCT02204072 | Sponsor: Boehringer Ingelheim | "In the Phase Ib escalation (n = 10), no dose-limiting toxicities were reported, and xentuzumab 1000 mg weekly plus enzalutamide 160 mg daily (Xe1000 + En160) was defined as the MTD and recommended Phase 2 dose. In the Phase Ib expansion (n = 24), median PFS was 8.2 months, and one patient had a confirmed, long-term response. In Phase II (n = 86), median PFS for the Xe1000 + En160 and En160 arms was 7.4 and 6.2 months, respectively. Subgroup analysis suggested trends towards benefit with Xe1000 + En160 in patients whose tumours had high levels of IGF1 mRNA or PTEN protein. Overall, the combination was well tolerated."

P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Phase Ib/II study of IGF-neutralising antibody xentuzumab with enzalutamide in metastatic castration-resistant prostate cancer (Nature, Br J Cancer) - P1b/2 | N=120 | NCT02204072 | Sponsor: Boehringer Ingelheim | "In the Phase Ib escalation (n = 10), no dose-limiting toxicities were reported, and xentuzumab 1000 mg weekly plus enzalutamide 160 mg daily (Xe1000 + En160) was defined as the MTD and recommended Phase 2 dose. In the Phase Ib expansion (n = 24), median PFS was 8.2 months, and one patient had a confirmed, long-term response. In Phase II (n = 86), median PFS for the Xe1000 + En160 and En160 arms was 7.4 and 6.2 months, respectively. Subgroup analysis suggested trends towards benefit with Xe1000 + En160 in patients whose tumours had high levels of IGF1 mRNA or PTEN protein. Overall, the combination was well tolerated."

P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Weekly Intravenous Administrations of BI 836845 in Japanese Patients With Advanced Solid Tumours (clinicaltrials.gov) - P1 | N=21 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Metastases • Trial completion • Oncology • Solid Tumor

BI836845 Plus Enzalutamide in Castrate Resistant Prostate Cancer (CRPC) (clinicaltrials.gov) - P1 | N=120 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

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) - P2 | "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."

Combination therapy • Journal • Metastases • P2 data • Breast Cancer • Diabetes • Fatigue • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Pain • Solid Tumor • HER-2 • IGF1 • IGF2

WINGMEN: Windows Trial of INsulin-like Growth Factor Neutralising Antibody Xentuzumab in MEN Scheduled for Radical Prostatectomy (clinicaltrials.gov) - P1 | N=27 | Active, not recruiting | Sponsor: University of Oxford | Recruiting ➔ Active, not recruiting

Enrollment closed • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

[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) - P2 | "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 • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • IGF1 • IGF1R • IGF2 • IR

[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) - P2 | "Funding: Boehringer Ingelheim. Clinical trial identification: 2017-003131-11/NCT03659136."

Clinical • Combination therapy • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Pain • Solid Tumor • HER-2 • IGF1

[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) - P2 | "Funding: Boehringer Ingelheim. Clinical trial identification: 2017-003131-11/NCT03659136."

Clinical • Combination therapy • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Pain • Solid Tumor • HER-2 • IGF1

Integrated analysis and clinical correlation analysis of hub genes, immune infiltration, and potential therapeutic agents related to lupus nephritis. (PubMed, Lupus) - "We analyzed the transcriptomic signature of LN along with the landscape of the immune cell. FOS and IGF1 are promising biomarkers for diagnosing and evaluating the progression of LN. The drug-gene interaction analyses provide a list of candidate drugs for the precise treatment of LN."

Journal • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Systemic Lupus Erythematosus • IGF1

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 • Gastrointestinal Cancer • Hepatoblastoma • Hepatology • Liver Cancer • Oncology • Pediatrics • Solid Tumor • IGF1 • IGF2 • MIR483

Weekly Intravenous Administrations of BI 836845 in Japanese Patients With Advanced Solid Tumours (clinicaltrials.gov) - P1 | N=21 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Sep 2022 ➔ Jul 2023

Trial completion date • Oncology • Solid Tumor

BI836845 Plus Enzalutamide in Castrate Resistant Prostate Cancer (CRPC) (clinicaltrials.gov) - P1 | N=120 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Aug 2022 ➔ Jul 2023

Combination therapy • Trial completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

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 | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PGR

Identification of IGF2 as genomic driver and actionable therapeutic target in hepatoblastoma (AACR 2022) - "IGF2 is an actionable driver in HB and its overexpression was associated with fetal promoter hypomethylation, LOH or miR483 overexpression. The combination of a mAb against IGF1/2 (xentuzumab) with cisplatin led to remarkable anti-tumoral effects in pre-clinical models, providing the rationale for exploring this regimen in IGF2high HB patients."

Gastrointestinal Cancer • Hepatoblastoma • Liver Cancer • Oncology • Solid Tumor • CTNNB1 • IGF1 • IGF2 • MIR483 • TGFB1

WINGMEN: Windows Trial of INsulin-like Growth Factor Neutralising Antibody Xentuzumab in MEN Scheduled for Radical Prostatectomy (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: University of Oxford | Not yet recruiting ➔ Recruiting

Enrollment open • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Weekly Intravenous Administrations of BI 836845 in Japanese Patients With Advanced Solid Tumours (clinicaltrials.gov) - P1 | N=21 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Mar 2022 ➔ Sep 2022

Trial completion date • Oncology • Solid Tumor

BI 836845 in Estrogen Receptor Positive Metastatic Breast Cancer (clinicaltrials.gov) - P1; N=164; Completed; Sponsor: Boehringer Ingelheim; Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

A phase 1 trial of xentuzumab, an IGF-neutralizing antibody, in Japanese patients with advanced solid tumors. (PubMed, Cancer Sci) - P1 | "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 • Journal • P1 data • Fatigue • Fibrosis • Hematological Disorders • Neutropenia • Oncology • Sarcoma • Solid Tumor • IGF1 • IGF2

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 • Breast Cancer • Oncology • Solid Tumor • RRM2