BI 905711 / Boehringer Ingelheim - LARVOL DELTA

A Study to Find the Best Dose of BI 905711 in Combination With Chemotherapy and to Test Whether This Dose Helps People With Advanced Gastrointestinal Cancers (clinicaltrials.gov) - P1 | N=13 | Completed | Sponsor: Boehringer Ingelheim | Terminated ➔ Completed

Combination therapy • Metastases • Trial completion • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Study to Find a Safe and Effective Dose of BI 905711 in Patients With Advanced Gastrointestinal Cancer (clinicaltrials.gov) - P1 | N=110 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Metastases • Trial completion • Biliary Cancer • Cholangiocarcinoma • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gallbladder Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A Study to Find the Best Dose of BI 905711 in Combination With Chemotherapy and to Test Whether This Dose Helps People With Advanced Gastrointestinal Cancers (clinicaltrials.gov) - P1 | N=13 | Terminated | Sponsor: Boehringer Ingelheim | Phase classification: P1a/1b ➔ P1 | Trial completion date: Mar 2024 ➔ Oct 2023 | Active, not recruiting ➔ Terminated; Company decision

Combination therapy • Metastases • Phase classification • Trial completion date • Trial termination • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Study to Find a Safe and Effective Dose of BI 905711 in Patients With Advanced Gastrointestinal Cancer (clinicaltrials.gov) - P1 | N=110 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial primary completion date: Jan 2024 ➔ Jul 2023

Trial primary completion date • Biliary Cancer • Cholangiocarcinoma • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gallbladder Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A Study to Find the Best Dose of BI 905711 in Combination With Chemotherapy and to Test Whether This Dose Helps People With Advanced Gastrointestinal Cancers (clinicaltrials.gov) - P1a/1b | N=13 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial primary completion date: Mar 2024 ➔ Oct 2023

Combination therapy • Metastases • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Study to Find the Best Dose of BI 905711 in Combination With Chemotherapy and to Test Whether This Dose Helps People With Advanced Gastrointestinal Cancers (clinicaltrials.gov) - P1a/1b | N=13 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Sep 2023 ➔ Sep 2024 | Trial primary completion date: Sep 2023 ➔ Mar 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Study to Find the Best Dose of BI 905711 in Combination With Chemotherapy and to Test Whether This Dose Helps People With Advanced Gastrointestinal Cancers (clinicaltrials.gov) - P1a/1b | N=13 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Sep 2024 ➔ Mar 2024

Combination therapy • Metastases • Trial completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A phase Ia/Ib, open-label, dose escalation study of the TRAILR2 agonist BI 905711 in combination with chemotherapy (CT) in patients (pts) with advanced GI cancers. (ASCO-GI 2023) - P1a/1b | " This Phase Ia/Ib, open-label, multicenter study (NCT05087992) aims to determine the maximum tolerated dose (MTD), recommended dose for expansion (RDE), pharmacokinetics (PK), and efficacy of BI 905711 with CT (FOLFIRI; irinotecan, leucovorin, and fluorouracil) ± bevacizumab (BEV) in pts with advanced GI cancers...In the CRC cohort, pts with prior progression on oxaliplatin-based therapy will be randomized 2:1 to receive FOLFIRI and BEV ± BI 905711. In the PDAC cohort, pts with CDH17+ PDAC with prior progression on gemcitabine-based first-line therapy will receive FOLFIRI + BI 905711...The study is ongoing. Clinical trial information: NCT05087992."

Clinical • Combination therapy • Metastases • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CDH2 • TNFRSF10B

A Study to Find the Best Dose of BI 905711 in Combination With Chemotherapy and to Test Whether This Dose Helps People With Advanced Gastrointestinal Cancers (clinicaltrials.gov) - P1a/1b | N=13 | Active, not recruiting | Sponsor: Boehringer Ingelheim | N=10 ➔ 13

Combination therapy • Enrollment change • Metastases • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Study to Find the Best Dose of BI 905711 in Combination With Chemotherapy and to Test Whether This Dose Helps People With Advanced Gastrointestinal Cancers (clinicaltrials.gov) - P1a/1b | N=10 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting | N=100 ➔ 10 | Trial completion date: Nov 2024 ➔ Sep 2023 | Trial primary completion date: Jun 2024 ➔ Sep 2023

Combination therapy • Enrollment change • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Study to Find a Safe and Effective Dose of BI 905711 in Patients With Advanced Gastrointestinal Cancer (clinicaltrials.gov) - P1 | N=110 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2024 ➔ Sep 2023

Enrollment closed • Metastases • Trial completion date • Biliary Cancer • Cholangiocarcinoma • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gallbladder Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

[VIRTUAL] BI 905711 selectively induces apoptosis and anti-tumor response in TRAILR2/CDH17- expressing pancreatic cancer models (AACR 2021) - P1 | "Responders to BI 905711 were identified primarily within the classical and quasi-basal/hybrid subtypes when TRAILR2 was adequately co-expressed. This correlates with an enrichment pattern of CDH17 gene expression that is mostly within the classical gene cluster and strongly anti-correlated with basal-like cluster enrichment.Robust preclinical anti-tumor activity of BI 905711 in TRAILR2 and CDH17-expressing PDAC PDX models, along with this antibody’s potential for a favorable safety profile, has justified the enrollment of pancreatic cancer patients in the ongoing BI 905711 FIH Phase I clinical trial (NCT04137289)."

Preclinical • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CASP7 • TNFA • TNFRSF10B

A phase Ia/b first-in-human, open-label, multicenter study of BI 905711, a bispecific TRAILR2 agonist, in patients with advanced gastrointestinal cancers. (ASCO-GI 2023) - P1 | "In heavily pretreated pts, BI 905711 was associated with a tolerable safety profile and early signs of disease control. BI 905711 will be further assessed in Phase Ib in 4 dose groups: 0.6/1.2/2.4 mg/kg every 14 days, and 0.6 mg/kg weekly. Clinical trial information: NCT04137289."

Clinical • Metastases • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CASP3 • CASP7 • TNFRSF10B

A Study to Find a Safe and Effective Dose of BI 905711 in Patients With Advanced Gastrointestinal Cancer (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Jun 2023 ➔ Jun 2024

Trial completion date • Biliary Cancer • Cholangiocarcinoma • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gallbladder Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A phase Ia/Ib, open-label, dose-escalation study of the TRAILR2 agonist BI 905711 in combination with chemotherapy in patients with advanced gastrointestinal cancers (ESMO-GI 2022) - P1a/1b | "In preclinical models of GI cancer, including colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC), BI 905711 showed activity both as a single agent and in combination with chemotherapeutic agents (Garcia-Martinez et al., Mol Cancer Ther 2021; 20:96–108). Preclinical studies also showed synergism of BI 905711 and SoC chemotherapy, particularly irinotecan."

Clinical • Combination therapy • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • TNFRSF10B

A phase Ia/b, open-label, multicentre study of the TRAILR2 agonist BI 905711 in patients (pts) with advanced gastrointestinal (GI) cancers (ESMO 2022) - P1 | "Conclusions BI 905711 showed a tolerable safety profile with favourable PK properties. Early signs of disease control in these heavily pretreated pts was observed and will be further assessed in phase Ib in 4 dose groups: 0.6/1.2/2.4 mg/kg every 14 days, and 0.6 mg/kg weekly."

Clinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • CASP3 • CASP7 • TNFRSF10B

A first-in-human phase Ia/b, open-label, multicenter study of the TRAILR2 agonist BI 905711 in patients (pts) with advanced gastrointestinal (GI) cancers. (ASCO-GI 2022) - P1 | "In preclinical assays, BI 905711 demonstrated a potency shift of ̃1000 fold versus the 1st-generation TRAILR2 agonist lexatumumab. Secondary endpoints include PK parameters and OR in pts with measurable disease (phase Ia), and disease control, tumor shrinkage, duration of response, and progression-free survival (phase Ib). Trial enrollment is ongoing, with 33 pts enrolled to date."

Clinical • P1 data • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Gallbladder Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Small Intestinal Carcinoma • TNFRSF10B

A Study to Find a Safe and Effective Dose of BI 905711 in Patients With Advanced Gastrointestinal Cancer (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Mar 2023 ➔ Jun 2023

Trial completion date • Biliary Cancer • Cholangiocarcinoma • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gallbladder Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A Study to Find the Best Dose of BI 905711 in Combination With Chemotherapy and to Test Whether This Dose Helps People With Advanced Gastrointestinal Cancers (clinicaltrials.gov) - P1a/1b; N=100; Recruiting; Sponsor: Boehringer Ingelheim; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

A Study to Find the Best Dose of BI 905711 in Combination With Chemotherapy and to Test Whether This Dose Helps People With Advanced Gastrointestinal Cancers (clinicaltrials.gov) - P1a/1b; N=100; Not yet recruiting; Sponsor: Boehringer Ingelheim

Clinical • Combination therapy • New P1 trial • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

[VIRTUAL] A first-in-human phase Ia/b, open-label, multicentre, dose-escalation study of BI 905711 in patients with advanced gastrointestinal cancers (ESMO-GI 2020) - P1 | "Legal entity responsible for the study The authors. Funding Boehringer Ingelheim."

Clinical • P1 data • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

"Yes, an actual novel target: Uni of Penn licenses anti-CDH17 Car to Chimeric Therapeutics https://t.co/ZYlRbSnJlF Boehringer has BI 905711, TRAILR2 x CDH17 bispecific MAb, in ph1" (@JacobPlieth)

TNFRSF10B

"BI 905711, a bispecific antibody targeting TRAILR2 and CDH17, has potent and selective #AntitumorActivity in CDH17-positive #ColorectalCancer models both in vitro and in vivo. Paper by Garcia-Martinez. @Boehringer @JM_GaMar @norbertkraut1 https://t.co/TsUeOOASi8" (@MCT_AACR)

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Selective tumor cell apoptosis and tumor regression in CDH17-positive colorectal cancer models using BI 905711, a novel liver-sparing TRAILR2 agonist. (PubMed, Mol Cancer Ther) - P1 | "BI 905711 demonstrated single-agent tumor regressions in CDH17-positive CRC xenografts, an effect that was further enhanced upon combination with irinotecan. 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 percent CDH17-positive tumors in CRC patients, the molecule preclinical efficacy together with its potential for a favorable safety profile, support the ongoing BI 905711 phase I trial in CRC and additional CDH17-positive cancer types (NCT04137289)."

Journal • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor

Boehringer Ingelheim Advances Novel Bi-specific TRAILR2/CDH17 Antibody to Phase 1 Clinical Trial for Patients Living with Gastrointestinal Cancers (Businesswire) - "Boehringer Ingelheim today announced the advancement of the bi-specific and tetravalent therapeutic antibody, BI 905711, to its first-in-human clinical trial for patients with advanced gastrointestinal (GI) cancers. The first-in-class BI 905711 antibody is designed to recognize both the pro-apoptotic tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor 2 (TRAILR2) and the tumor cell anchor cadherin 17 (CDH17) to activate the self-destruction (apoptosis) pathway in co-expressing tumor cells found mostly in the GI tract. For patients suffering from these types of cancers, the advancement of the Phase 1 trial marks an important milestone in the continuing development of more tolerable innovative therapies to address diseases with high unmet need."

Trial status • Gastrointestinal Cancer • Oncology