Delving into the Latest Updates on Xentuzumab with Synapse

Overview

Basic Info

Drug Type

Bispecific antibody

Synonyms

BI-836845

Target

IGF-1 x IGF-2

Action

inhibitors

Mechanism

IGF-1 inhibitors(Insulin-like growth factor I inhibitors), IGF-2 inhibitors(Insulin-like growth factor II inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication

Hormone receptor positive HER2 positive breast cancer

Inactive Indication

Adenocarcinoma of prostateAdvanced Malignant Solid NeoplasmEGFR-mutated non-small Cell Lung Cancer+ [6]

Originator Organization

C.H. Boehringer Sohn AG & Co. KG

Active Organization

Boehringer Ingelheim GmbH

Inactive Organization-

License Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 164717H

Source: *****

Sequence Code 164724L

Source: *****

The WINGMEN trial aims to understand how a hormone-like protein called insulin-like growth factor (IGF) helps prostate cancers grow and become aggressive. IGF is required for normal development, and also helps cancers grow and spread. Men with high blood IGF are at increased risk of developing prostate cancer, and tall men are more likely to get aggressive prostate cancer. The WINGMEN trial will recruit 30 men with prostate cancer who have been offered an operation to remove the prostate. Most men have to wait 4-5 weeks between a decision to have prostate removal surgery, and actually having the operation. In this 4-5 week window we will offer treatment with a new IGF-blocker drug called xentuzumab. The drug is provided by Boehringer Ingelheim and the trial is funded by Prostate Cancer UK.
Xentuzumab will be given as an outpatient by once weekly intravenous infusion (drip) in the Early Phase Clinical Trials Unit, Oxford Cancer Centre, Churchill Hospital. In other trials, xentuzumab is being tested in patients with advanced cancer, and is proving to be well-tolerated. After the 4-week treatment, WINGMEN trial patients will have routine prostate removal surgery. Samples of blood and prostate cancer that are surplus to diagnostic need will be taken from the diagnostic prostate biopsy (pre-xentuzumab) and the cancer removed at surgery (after xentuzumab) for research tests. These samples will be compared to measure how effectively xentuzumab reduces signs of tumour growth, and identify which genes and proteins are switched on or off by xentuzumab, and which may therefore be important in helping IGF promote prostate cancer growth. The information we get from the WINGMEN trial may help us to improve treatment of men with prostate cancer, with the long-term aim of reducing the risk of aggressive prostate cancer

Start Date17 Dec 2021

Sponsor / Collaborator

University of Oxford

[+2]

NCT03659136

/ CompletedPhase 2

XENERA™1: A Multi-centre, Double-blind, Placebo-controlled, Randomised Phase II Trial to Compare Efficacy of Xentuzumab in Combination With Everolimus and Exemestane Versus Everolimus and Exemestane in Women With HR+ / HER2- Metastatic Breast Cancer and Non-visceral Disease

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.

Start Date28 Nov 2018

Sponsor / Collaborator

Boehringer Ingelheim GmbH

NCT03099174

/ CompletedPhase 1

An Open Label, Phase Ib, Dose-escalation Study Evaluating the Safety and Tolerability of Xentuzumab and Abemaciclib in Patients With Locally Advanced or Metastatic Solid Tumours and in Combination With Endocrine Therapy in Patients With Locally Advanced or Metastatic Hormone Receptor-positive, HER2-, Breast Cancer, Followed by Expansion Cohorts.

This is a study in adult patients with different types of cancer. The purpose of this study is to find a safe dose of:
* Xentuzumab in combination with abemaciclib
* Xentuzumab in combination with abemaciclib and hormonal therapies The study also tests whether these medicines make tumours shrink in participants with lung and breast cancer.
Participants can stay in the study as long as they benefit from and can tolerate treatment. All participants get xentuzumab infusions and abemaciclib tablets. Participants who have breast cancer get different types of hormonal therapies in addition to xentuzumab and abemaciclib.
For all participants, the size of the tumour is measured regularly. Doctors also regularly check the general health of the participants."

Start Date04 May 2017

Sponsor / Collaborator

Boehringer Ingelheim GmbH

100 Clinical Results associated with Xentuzumab

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100 Translational Medicine associated with Xentuzumab

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100 Patents (Medical) associated with Xentuzumab

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18

Literatures (Medical) associated with Xentuzumab

05 Oct 2023·British journal of cancer

A Phase Ib/II study of IGF-neutralising antibody xentuzumab with enzalutamide in metastatic castration-resistant prostate cancer

Article

Author: Schlieker, Laura ; Lin, Chia-Chi ; Bianchini, Diletta ; de Bono, Johann ; Lord, Simon ; Hussain, Syed ; Maroto, José Pablo ; Climent, Miguel Ángel ; Wang, Shian-Shiang ; Cook, Natalie ; Macaulay, Valentine M ; Bogenrieder, Thomas ; Bailey, Mark ; Jones, Robert Hugh

Abstract:

Background:

This multicentre, open-label, Phase Ib/II trial evaluated the insulin-like growth factor (IGF) 1/2 neutralising antibody xentuzumab plus enzalutamide in metastatic castrate-resistant prostate cancer (mCRPC).

Methods:

The trial included Phase Ib escalation and expansion parts and a randomised Phase II part versus enzalutamide alone. Primary endpoints in the Phase Ib escalation, Phase Ib expansion and Phase II parts were maximum tolerated dose (MTD), prostate-specific antigen response and investigator-assessed progression-free survival (PFS), respectively. Patients in the Phase Ib escalation and Phase II parts had progressed on/after docetaxel/abiraterone.

Results:

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.

Conclusions:

Xentuzumab plus enzalutamide was tolerable but lacked antitumour activity in unselected patients with mCRPC.

Clinical trial registration:

EudraCT number 2013-004011-41.

12 Jun 2023·Breast cancer research : BCR

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.

Article

Author: Massey, Dan ; Jañez, Noelia Martínez ; Blau, Sibel ; Morales, Serafín ; Burris, Howard A ; Baktash, Navid ; Lemieux, Julie ; Joaquim, Ana ; Hart, Lowell ; Díaz-Redondo, Tamara ; Rugo, Hope S ; García-Sáenz, José Ángel ; Schmid, Peter ; Cortes, Javier ; Biyukov, Tsvetan ; Neven, Patrick

BACKGROUND:

Xentuzumab is a humanised monoclonal antibody that binds to IGF-1 and IGF-2, neutralising their proliferative activity and restoring inhibition of AKT by everolimus. This study evaluated the addition of xentuzumab to everolimus and exemestane in patients with advanced breast cancer with non-visceral disease.

METHODS:

This double-blind, randomised, Phase II study was undertaken in female patients with hormone-receptor (HR)-positive/human epidermal growth factor 2 (HER2)-negative advanced breast cancer with non-visceral disease who had received prior endocrine therapy with or without CDK4/6 inhibitors. Patients received a weekly intravenous infusion of xentuzumab (1000 mg) or placebo in combination with everolimus (10 mg/day orally) and exemestane (25 mg/day orally). The primary endpoint was progression-free survival (PFS) per independent review.

RESULTS:

A total of 103 patients were randomised and 101 were treated (n = 50 in the xentuzumab arm and n = 51 in the placebo arm). The trial was unblinded early due to high rates of discordance between independent and investigator assessment of PFS. Per independent assessment, median PFS was 12.7 (95% CI 6.8-29.3) months with xentuzumab and 11.0 (7.7-19.5) months with placebo (hazard ratio 1.19; 95% CI 0.55-2.59; p = 0.6534). Per investigator assessment, median PFS was 7.4 (6.8-9.7) months with xentuzumab and 9.2 (5.6-14.4) months with placebo (hazard ratio 1.23; 95% CI 0.69-2.20; p = 0.4800). Tolerability was similar between the arms, with diarrhoea (33.3-56.0%), fatigue (33.3-44.0%) and headache (21.6-40.0%) being the most common treatment-emergent adverse events. The incidence of grade ≥ 3 hyperglycaemia was similar between the xentuzumab (2.0%) and placebo (5.9%) arms.

CONCLUSIONS:

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.

03 Apr 2023·Molecular cancer therapeutics

Identification ofIGF2as Genomic Driver and Actionable Therapeutic Target in Hepatoblastoma

Article

Author: Armengol, Carolina ; Cairo, Stefano ; Pinyol, Roser ; Morland, Bruce ; Sia, Daniela ; Torres-Martin, Miguel ; Childs, Margaret ; Andreu-Oller, Carmen ; Puigvehi, Marc ; Maibach, Rudolf ; Domingo-Sàbat, Montserrat ; Losic, Bojan ; Royo, Laura ; Haber, Philipp K. ; Guccione, Ernesto ; Czauderna, Piotr ; Akers, Nicholas K. ; Torrens, Laura ; Llovet, Josep M. ; Rialdi, Alex ; Montironi, Carla ; Peix, Judit ; Willoughby, Catherine E. ; Balaseviciute, Ugne ; Alaggio, Rita ; Carrillo-Reixach, Juan ; Del Río-Álvarez, Álvaro ; Mazzaferro, Vincenzo ; Abril-Fornaguera, Jordi

Abstract:

Management of hepatoblastoma (HB), the most frequent pediatric liver cancer, is based on surgical resection and perioperative chemotherapy regimens. In this study, we aimed to identify actionable targets in HB and assess the efficacy of molecular therapies in preclinical models of HB. Paired tumor and adjacent tissues from 31 HBs and a validation set of 50 HBs were analyzed using RNA-seq, SNP, and methylation arrays. IGF2 overexpression was identified as the top targetable HB driver, present in 71% of HBs (22/31). IGF2high tumors displayed progenitor cell features and shorter recurrence-free survival. IGF2 overexpression was associated in 91% of cases with fetal promoter hypomethylation, ICR1 deregulation, 11p15.5 loss of heterozygosity or miR483-5p overexpression. 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. The combination of xentuzumab with cisplatin showed strong synergistic antitumor effects in organoids and in IGF2high cell lines. In mice (n = 55), the combination induced a significant decrease in tumor volume and improved survival compared with cisplatin alone. 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.

100 Deals associated with Xentuzumab

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hormone receptor positive HER2 negative breast cancer	Phase 2	United States	Boehringer Ingelheim GmbH	28 Nov 2018
Hormone receptor positive HER2 negative breast cancer	Phase 2	Australia	Boehringer Ingelheim GmbH	28 Nov 2018
Hormone receptor positive HER2 negative breast cancer	Phase 2	Belgium	Boehringer Ingelheim GmbH	28 Nov 2018
Hormone receptor positive HER2 negative breast cancer	Phase 2	Canada	Boehringer Ingelheim GmbH	28 Nov 2018
Hormone receptor positive HER2 negative breast cancer	Phase 2	France	Boehringer Ingelheim GmbH	28 Nov 2018
Hormone receptor positive HER2 negative breast cancer	Phase 2	Germany	Boehringer Ingelheim GmbH	28 Nov 2018
Hormone receptor positive HER2 negative breast cancer	Phase 2	Greece	Boehringer Ingelheim GmbH	28 Nov 2018
Hormone receptor positive HER2 negative breast cancer	Phase 2	Italy	Boehringer Ingelheim GmbH	28 Nov 2018
Hormone receptor positive HER2 negative breast cancer	Phase 2	Portugal	Boehringer Ingelheim GmbH	28 Nov 2018
Hormone receptor positive HER2 negative breast cancer	Phase 2	Spain	Boehringer Ingelheim GmbH	28 Nov 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02204072 (CTgov)	Phase 1	Metastatic castration-resistant prostate cancer	120	Enzalutamide+Xentuzumab (Phase Ib Escalation: 750 mg Xentuzumab + 160 mg Enzalutamide)	ygviizmxhw = oqaewbspnu xwotkzanfu (gnouuljpwv, iudopnpvpl - yrcacklexm) View more	-	15 Jul 2025
				Enzalutamide+Xentuzumab (Phase Ib Escalation: 1000 mg Xentuzumab + 160 mg Enzalutamide)	ygviizmxhw = ljhalqiwoi xwotkzanfu (gnouuljpwv, mijzjjyrnh - mgfujfibrz) View more
NCT02123823 (Study 1280.4, CTgov)	Phase 1	Locally advanced breast cancer \| Estrogen receptor positive breast cancer	164	Exemestane+Everolimus+BI 836845 (Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II)	zcicfzmfru(nrywduruto) = avowuwyjxd qjjfbjitgw (tapkjdvkve, htsilgtteo - lgupaawrxy) View more	-	15 Jul 2025
				Exemestane+Everolimus (Everolimus 10 mg + Exemestane 25 mg - Phase II)	zcicfzmfru(nrywduruto) = phttvgzjap qjjfbjitgw (tapkjdvkve, pmdozuhuch - jycacmubal) View more
NCT02191891 (CTgov)	Phase 1	EGFR-mutated non-small Cell Lung Cancer	32	Afatinib+Xentuzumab (Xentuzumab + Afatinib 30 Milligram (mg) - Part A)	mrwvszwaaz = kjvglgguwy zwacpoespn (hzjjxnxczi, dmedzvqdqq - ognthglhlg)	-	25 Jun 2025
				Afatinib+Xentuzumab (Xentuzumab + Afatinib 40 mg - Part A)	mrwvszwaaz = yfjmakfgeo zwacpoespn (hzjjxnxczi, clpwmtdzwr - jvcatdnznk)
NCT03099174 (P3-11-05, CTgov)	Phase 1	Hormone receptor positive HER2 positive breast cancer	133	abemaciclib+Xentuzumab (Cohort A: Xentuzumab 1000 mg & 150 mg Abemaciclib)	tahcispfoo = zxsyuavwru qqrejaxcou (bgwybwbuen, cvdjoabxdw - miydvyembm) View more	-	24 Jun 2025
				Letrozole+abemaciclib+Xentuzumab (Cohort B: Xentuzumab 1000 mg & 150 mg Abemaciclib & 2.5 mg Letrozole)	tahcispfoo = dfrohtqvfo qqrejaxcou (bgwybwbuen, gztqpglmxz - wbisxetycq) View more
NCT02145741 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm	21	Xentuzumab (BI 836845 (Xentuzumab (BI 836845))	qiopptrjqo = cqhwnfavvc wrjltlccld (ivdttmzxhh, jrvxntrofv - sgorernbiq)	-	19 Jun 2025
				Xentuzumab (BI 836845 (750 Milligram Xentuzumab (BI 836845))	cycmyizkry(mckfxedhbf) = wflpguqanc quxnhdqmzt (eeevcnfjdw, fzgjzlvtew - rgqbixqxdv) View more
NCT05110495 (WINGMEN, CTgov)	Early Phase 1	Prostatic Cancer \| Prostate Cancer, Hereditary, 7 \| Adenocarcinoma of prostate	27	Xentuzumab	pihqmoupki(knjckaklzn) = kyshrjkcya uftciznvfy (jbektbguqd, shmkxfjtap - ubjgrrsrqp) View more	-	17 Feb 2025
NCT03659136 (XENERA-1, Pubmed)	Phase 2	Hormone receptor positive HER2 negative breast cancer	103	Xentuzumab	skbahdcqne(ggptiylfwe) = ozlgpqumss prwlazzpqw (loikgfxgfj, 6.8 - 29.3) View more	Negative	12 Jun 2023
				Placebo	skbahdcqne(ggptiylfwe) = krkqlerysf prwlazzpqw (loikgfxgfj, 7.7 - 19.5) View more
NCT03659136 (XENERA-1, CTgov)	Phase 2	Metastatic breast cancer \| Hormone receptor positive HER2 negative breast cancer	103	Exemestane+Everolimus+Xentuzumab (1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane)	sjqdnmdgzr(spltddfxek) = slzabuxzfx wzxsjudrpp (ejjpczpkvp, fnacuwojus - uobzvjvhab) View more	-	29 Sep 2022
				Placebo+Exemestane+Everolimus (Placebo + 10 mg Everolimus + 25 mg Exemestane)	sjqdnmdgzr(spltddfxek) = eyzfaxllvj wzxsjudrpp (ejjpczpkvp, cenkyaxdnh - jvcqeqnzja) View more
NCT02145741 (Pubmed \| Cancer Sci) Manual	Phase 1	Solid tumor	21	xentuzumab	rngvmpvvtf(cgtlllrgny) = There were no dose-limiting toxicities at any dose. gmakgnoben (ncadycpuji ) View more	Positive	06 Dec 2021
NCT02191891 (Pubmed) Manual	Phase 1	EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma EGFR Positive \| EGFR T790M Negative	32	Afatinib+Xentuzumab (part A)	zadixwjslu(ajuwgderob) = Maximum tolerated dose was xentuzumab 1000 mg/wk plus afatinib 40 mg/d. dfbdxhhbig (olshizyzde ) View more	Negative	10 Jul 2021
				Afatinib+Xentuzumab (part B)

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Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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Xentuzumab

Overview

Basic Info

Structure/Sequence

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Biosimilar

Regulation