Delving into the Latest Updates on BI-905711 with Synapse

Overview

Basic Info

Drug Type

Bispecific antibody

Synonyms

Target

Mechanism

CDH17 antagonists(Cadherin-17 antagonists), DR5 agonists(Tumor necrosis factor receptor superfamily member 10B agonists)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication

Gastrointestinal NeoplasmsGastrointestinal cancer metastaticBile Duct Neoplasms+ [3]

Inactive Indication

Diffuse Large B-Cell Lymphoma

Originator Organization

Boehringer Ingelheim GmbH

Active Organization

Boehringer Ingelheim GmbH

Memorial Sloan Kettering Cancer Center

The University of Texas MD Anderson Cancer Center

+ [1]

Inactive Organization

Boehringer Ingelheim (China) Investment Co., Ltd.Boehringer Ingelheim International GmbHBoehringer Ingelheim Pharma GmbH & Co., KG

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Ia 期：基于最大耐受剂量（MTD）评估期间患者出现剂量限制性毒性（DLT）的频率，确定BI 905711 联合FOLFIRI 方案 + 贝伐珠单抗治疗在CRC 患者中的MTD 和推荐的扩展期给药剂量（RDE）。探索BI 905711 联合FOLFIRI + 贝伐珠单抗治疗的药代动力学/药效学和有效性特征，以指导确定MTD 或在无MTD 情况下的潜在有效剂量。 Ib 期：评价BI 905711 联合FOLFIRI + 贝伐珠单抗在CRC 队列中的有效性和安全性，并确定RP2D。评价BI 905711 联合FOLFIRI 治疗在PDAC 队列中的有效性和安全性，并确定RP2D。

[Translation]

Phase Ia: Based on the frequency of dose-limiting toxicity (DLT) in patients during the maximum tolerated dose (MTD) evaluation, determine the MTD and recommended dose extension (RDE) of BI 905711 combined with FOLFIRI + bevacizumab in CRC patients. Explore the pharmacokinetic/pharmacodynamic and efficacy characteristics of BI 905711 combined with FOLFIRI + bevacizumab treatment to guide the determination of MTD or potential effective dose in the absence of MTD. Phase Ib: Evaluate the efficacy and safety of BI 905711 combined with FOLFIRI + bevacizumab in the CRC cohort and determine the RP2D. Evaluate the efficacy and safety of BI 905711 combined with FOLFIRI treatment in the PDAC cohort and determine the RP2D.

Start Date04 Jan 2022

Sponsor / Collaborator

Boehringer Ingelheim (China) Investment Co., Ltd.

[+2]

NCT05087992 / CompletedPhase 1

A Phase Ia/Ib, Open Label, Multicentre, Dose Escalation Study of BI 905711 in Combination With Chemotherapy Followed by Expansion Cohorts in Patients With Advanced Gastrointestinal Cancers

This study is open to adults with advanced colorectal cancer or with advanced pancreatic cancer. The study has 2 parts. In the first part, participants with colorectal cancer get a medicine called BI 905711 combined with chemotherapy and bevacizumab. The purpose of the first part is to find the highest BI 905711 dose participants can tolerate. In the second part, participants with colorectal cancer or pancreatic cancer get BI 905711 combined with chemotherapy. Some participants also get bevacizumab. The second part tests whether BI 905711 makes tumours shrink. Participants get BI 905711, chemotherapy and bevacizumab about every 2 weeks as an infusion into a vein. Participants can stay in the study as long as they benefit from treatment and can tolerate it. The doctors regularly check the health of the participants and note any health problems that could have been caused by the study treatment. The doctors also monitor the size of the tumour.

Start Date24 Nov 2021

Sponsor / Collaborator

Boehringer Ingelheim GmbH

CTR20210107 / TerminatedPhase 1

BI 905711治疗晚期胃肠道癌症患者的首次用于人体的Ia/b期、开放、多中心、剂量递增研究

[Translation] A first-in-human Phase Ia/b, open-label, multicenter, dose-escalation study of BI 905711 in patients with advanced gastrointestinal cancer

Ia期：探索BI 905711的安全性，并确定最大耐受剂量（MTD）;探索药代动力学/药效动力学和有效性，在未确定MTD的情况下为确定Ib期的潜在有效剂量范围提供指导 Ib期：评价BI 905711在潜在有效剂量范围内的有效性和安全性，并确定RP2D（推荐的II期剂量）

[Translation]

Phase Ia: Explore the safety of BI 905711 and determine the maximum tolerated dose (MTD); explore pharmacokinetics/pharmacodynamics and efficacy, and provide guidance for determining the potential effective dose range for Phase Ib if the MTD is not determined Phase Ib: Evaluate the efficacy and safety of BI 905711 within the potential effective dose range and determine RP2D (recommended Phase II dose)

Start Date02 Jun 2021

Sponsor / Collaborator

Boehringer Ingelheim (China) Investment Co., Ltd.

[+2]

100 Clinical Results associated with BI-905711

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100 Translational Medicine associated with BI-905711

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100 Patents (Medical) associated with BI-905711

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1

Literatures (Medical) associated with BI-905711

01 Jan 2021·Molecular Cancer TherapeuticsQ2 · MEDICINE

Selective Tumor Cell Apoptosis and Tumor Regression in CDH17-Positive Colorectal Cancer Models using BI 905711, a Novel Liver-Sparing TRAILR2 Agonist

Q2 · MEDICINE

Article

Author: Hilberg, Frank ; Weishaeupl, Cordula ; Kroe-Barrett, Rachel ; Dutcher, Darrin ; Kuenkele, Klaus Peter ; Giragossian, Craig ; Rinnenthal, Joerg ; Gorman, Philip N. ; Wernitznig, Andreas ; Ho, Jason ; García-Martínez, Juan Manuel ; Chetta, Paolo ; Pinto, Catarina ; Pearson, Mark ; Wang, Shirley ; Tirapu, Iñigo ; Impagnatiello, Maria Antonietta ; Kraut, Norbert

AbstractActivation of TRAILR2 has emerged as an important therapeutic concept in cancer treatment. TRAILR2 agonistic molecules have only had limited clinical success, to date, due either to lack of efficacy or hepatotoxicity. BI 905711 is a novel tetravalent bispecific antibody targeting both TRAILR2 and CDH17 and represents a novel liver-sparing TRAILR2 agonist specifically designed to overcome the disadvantages of previous strategies. Here, we show that BI 905711 effectively triggered apoptosis in a broad panel of CDH17-positive colorectal cancer tumor cells in vitro. Efficient induction of apoptosis was dependent on the presence of CDH17, as exemplified by the greater than 1,000-fold drop in potency in CDH17-negative cells. BI 905711 demonstrated single-agent tumor regressions in CDH17-positive colorectal cancer xenografts, an effect that was further enhanced upon combination with irinotecan. Antitumor efficacy correlated with induction of caspase activation, as measured in both the tumor and plasma. Effective tumor growth inhibition was further demonstrated across a series of different colorectal cancer PDX models. BI 905711 induced apoptosis in both a cis (same cell) as well as trans (adjacent cell) fashion, translating into significant antitumor activity even in xenograft models with heterogeneous CDH17 expression. In summary, we demonstrate that BI 905711 has potent and selective antitumor activity in CDH17-positive colorectal cancer models both in vitro and in vivo. The high prevalence of over 95% CDH17-positive tumors in patients with colorectal cancer, the molecule preclinical efficacy together with its potential for a favorable safety profile, support the ongoing BI 905711 phase I trial in colorectal cancer and additional CDH17-positive cancer types (NCT04137289).

100 Deals associated with BI-905711

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Bile Duct Neoplasms	Phase 1	KR	Boehringer Ingelheim GmbH	11 Mar 2020
Bile Duct Neoplasms	Phase 1	JP	Boehringer Ingelheim GmbH	11 Mar 2020
Pancreatic Cancer	Phase 1	BE	Boehringer Ingelheim GmbH	11 Mar 2020
Pancreatic Cancer	Phase 1	US	Boehringer Ingelheim GmbH	11 Mar 2020
Pancreatic Cancer	Phase 1	DE	Boehringer Ingelheim GmbH	11 Mar 2020
Pancreatic Cancer	Phase 1	KR	Boehringer Ingelheim GmbH	11 Mar 2020
Pancreatic Cancer	Phase 1	ES	Boehringer Ingelheim GmbH	11 Mar 2020
Pancreatic Cancer	Phase 1	JP	Boehringer Ingelheim GmbH	11 Mar 2020
Pancreatic Cancer	Phase 1	FR	Boehringer Ingelheim GmbH	11 Mar 2020
Pancreatic Cancer	Phase 1	CN	Boehringer Ingelheim GmbH	11 Mar 2020

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04137289 (ASCO_GI2023) Manual	Phase 1	Gastrointestinal Neoplasms	48	BI 905711	(ttdupiiaax) = sazvlkodjp giazhsbggi (skwvpmotqm ) View more	Positive	24 Jan 2023
NCT04137289 (ASCO_GI2023) Manual	Phase 1	Gastrointestinal Neoplasms	48	BI 905711 (CRC)	(wxvpnubchy) = wfnovzxsvk kcsrvuzcbf (xjwdczjdsf ) View more	Positive	24 Jan 2023
NCT04137289 (ESMO2022) Manual	Phase 1	Gastrointestinal Neoplasms	45	BI 905711	(hpolmtdgkx) = 2–3 days (0.6–3.6 mg/kg dose) jjgqjnjgnj (gmmousoqaw ) View more	Positive	10 Sep 2022