BI 891065 / Boehringer Ingelheim - LARVOL DELTA

Combining BET inhibition with SMAC mimetics restricts tumor growth and triggers immune surveillance in preclinical cancer models. (PubMed, Cell Rep Med) - "We show that the combination of BI 891065, a monovalent oral SMACm antagonist of inhibitor of apoptosis protein 1 (cellular inhibitor of apoptosis protein 1 [cIAP1]), and BI 894999, a potent and selective oral BETi, significantly impaired cancer cell proliferation irrespective of tissue context. A multi-omic analysis using Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) and advanced flow cytometry of a syngeneic model of pancreatic ductal adenocarcinoma (PDAC) unveils distinct phenotypic correlations of augmented anti-tumor immunity and a substantially reduced immunosuppressive tumor microenvironment (TME). Collectively, this study presents BETi and SMACm as a promising drug combination for patients with cancer with a multi-layered impact on both tumor cell-intrinsic and TME-dependent mechanisms."

Journal • Preclinical • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

SMAC Mimetic as potential anti-fibrotic therapy in an in vivo model of Bleomycin-induced Pulmonary Fibrosis (ERS 2023) - "Oral administration of the SMAC mimetic (BI891065) was performed for 2 weeks. Our results suggest that the inhibition of cIAP1 by SMAC mimetic treatment ameliorates pulmonary fibrosis by promoting myofibroblast apoptosis.; General respiratory patient care; Cell and molecular biology"

Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Test Different Doses of BI 891065 Alone and in Combination With BI 754091 in Asian Patients With Different Types of Advanced Cancer (Solid Tumours) (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Monotherapy • Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

[VIRTUAL] SMAC mimetic and BET inhibitor - a promising combination for solid cancer treatment? (AACR 2021) - P1, P1a/1b | "Of the 60+ cancer cell lines, around 30% showed synergy when treated with the BI 891065 + BI 894999 combination, irrespective of indication. These preclinical in vitro and in vivo data are highlighting the potential of a SMACm/BETi combination for the treatment of solid cancers. The identification of patient selection markers for this combination will be necessary for advancing this concept into pivotal clinical trials."

Gastric Cancer • Gastrointestinal Cancer • Hematological Malignancies • Oncology • Pancreatic Cancer • Solid Tumor • BRD4 • HEXIM1 • TNFA • XIAP

A Study to Test Different Doses of BI 891065 Alone and in Combination With BI 754091 in Asian Patients With Different Types of Advanced Cancer (Solid Tumours) (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Jan 2023 ➔ Jul 2023 | Trial primary completion date: Jan 2023 ➔ Jul 2023

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study to Test Different Doses of BI 891065 Alone and in Combination With BI 754091 in Asian Patients With Different Types of Advanced Cancer (Solid Tumours) (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Aug 2022 ➔ Jan 2023 | Trial primary completion date: Aug 2022 ➔ Jan 2023

Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study to Test Different Doses of BI 891065 Alone and in Combination With BI 754091 in Asian Patients With Different Types of Advanced Cancer (Solid Tumours) (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Feb 2022 ➔ Aug 2022 | Trial primary completion date: Feb 2022 ➔ Aug 2022

Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Trial to Find the Safe Dose for BI 891065 Alone and in Combination With BI 754091 in Patients With Incurable Tumours or Tumours That Have Spread (clinicaltrials.gov) - P1; N=62; Terminated; Sponsor: Boehringer Ingelheim; Completed ➔ Terminated; Not due to safety reasons.

Clinical • Combination therapy • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study to Test Different Doses of BI 891065 Alone and in Combination With BI 754091 in Asian Patients With Different Types of Advanced Cancer (Solid Tumours) (clinicaltrials.gov) - P1; N=12; Active, not recruiting; Sponsor: Boehringer Ingelheim; Trial completion date: Aug 2021 ➔ Feb 2022; Trial primary completion date: Aug 2021 ➔ Feb 2022

Clinical • Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study to Test Different Doses of BI 891065 Alone and in Combination With BI 754091 in Asian Patients With Different Types of Advanced Cancer (Solid Tumours) (clinicaltrials.gov) - P1; N=12; Active, not recruiting; Sponsor: Boehringer Ingelheim; Trial completion date: Feb 2021 ➔ Jul 2021; Trial primary completion date: Feb 2021 ➔ Jul 2021

Clinical • Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor

A Trial to Find the Safe Dose for BI 891065 Alone and in Combination With BI 754091 in Patients With Incurable Tumours or Tumours That Have Spread (clinicaltrials.gov) - P1; N=62; Completed; Sponsor: Boehringer Ingelheim; Active, not recruiting ➔ Completed; Trial completion date: Jan 2022 ➔ Oct 2020; Trial primary completion date: Jan 2022 ➔ Sep 2020

Clinical • Combination therapy • Trial completion • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor

A Trial to Find the Safe Dose for BI 891065 Alone and in Combination With BI 754091 in Patients With Incurable Tumours or Tumours That Have Spread (clinicaltrials.gov) - P1; N=53; Active, not recruiting; Sponsor: Boehringer Ingelheim; N=38 ➔ 53

Clinical • Combination therapy • Enrollment change • Bladder Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor

A Trial to Find the Safe Dose for BI 891065 Alone and in Combination With BI 754091 in Patients With Incurable Tumours or Tumours That Have Spread (clinicaltrials.gov) - P1; N=38; Active, not recruiting; Sponsor: Boehringer Ingelheim; Recruiting ➔ Active, not recruiting; N=104 ➔ 38

Clinical • Combination therapy • Enrollment change • Enrollment closed • Bladder Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor

A Study to Test Different Doses of BI 891065 Alone and in Combination With BI 754091 in Asian Patients With Different Types of Advanced Cancer (Solid Tumours) (clinicaltrials.gov) - P1; N=12; Active, not recruiting; Sponsor: Boehringer Ingelheim; Recruiting ➔ Active, not recruiting

Clinical • Combination therapy • Enrollment closed • Monotherapy • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor

A Study to Test Different Doses of BI 891065 Alone and in Combination With BI 754091 in Asian Patients With Different Types of Advanced Cancer (Solid Tumours) (clinicaltrials.gov) - P1; N=12; Recruiting; Sponsor: Boehringer Ingelheim; N=24 ➔ 12; Trial completion date: Dec 2021 ➔ Feb 2021; Trial primary completion date: Dec 2021 ➔ Feb 2021

Clinical • Combination therapy • Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor

[VIRTUAL] Targeting IAP in cancer: BI 891065 a potent small molecule SMAC mimetic that synergizes with immune checkpoint inhibition (AACR-II 2020) - "The presented data demonstrate the potential of BI 891065 to facilitate tumor cell death and to enhance anti-tumor immune responses, and nominate the compound as an attractive combination partner in cancer therapy. Our results led to the identification of potentially novel modulators of SMAC mimetic sensitivity via genome-wide CRISPR/Cas9 drug sensitizer screens and suggest colorectal cancer as a promising indication for clinical positioning."

Checkpoint inhibition • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CASP8 • TNFA

A Trial to Find the Safe Dose for BI 891065 Alone and in Combination With BI 754091 in Patients With Incurable Tumours or Tumours That Have Spread (clinicaltrials.gov) - P1; N=104; Recruiting; Sponsor: Boehringer Ingelheim; Suspended ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Bladder Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

A Study to Test Different Doses of BI 891065 Alone and in Combination With BI 754091 in Asian Patients With Different Types of Advanced Cancer (Solid Tumours) (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Boehringer Ingelheim; Suspended ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Monotherapy • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Platform Trial Evaluating Safety and Efficacy of BI 754091 Anti- PD-1 Based Combination Therapies in PD-(L)1 naïve and PD- (L)1 Pretreated Patient Populations With Advanced/Metastatic Solid Tumours. (clinicaltrials.gov) - P2; N=260; Suspended; Sponsor: Boehringer Ingelheim; Trial completion date: Dec 2021 ➔ Feb 2023; Trial primary completion date: Dec 2021 ➔ Feb 2023

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Platform Trial Evaluating Safety and Efficacy of BI 754091 Anti- PD-1 Based Combination Therapies in PD-(L)1 naïve and PD- (L)1 Pretreated Patient Populations With Advanced/Metastatic Solid Tumours. (clinicaltrials.gov) - P2; N=260; Suspended; Sponsor: Boehringer Ingelheim; Recruiting ➔ Suspended

Clinical • Combination therapy • Trial suspension • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study to Test Different Doses of BI 891065 Alone and in Combination With BI 754091 in Asian Patients With Different Types of Advanced Cancer (Solid Tumours) (clinicaltrials.gov) - P1; N=24; Suspended; Sponsor: Boehringer Ingelheim; Recruiting ➔ Suspended

Trial suspension • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

A Trial to Find the Safe Dose for BI 891065 Alone and in Combination With BI 754091 in Patients With Incurable Tumours or Tumours That Have Spread (clinicaltrials.gov) - P1; N=104; Suspended; Sponsor: Boehringer Ingelheim; Recruiting ➔ Suspended

Trial suspension • Bladder Cancer • Genito-urinary Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • Urothelial Cancer

A Study to Test Different Doses of BI 891065 Alone and in Combination With BI 754091 in Asian Patients With Different Types of Advanced Cancer (Solid Tumours) (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Boehringer Ingelheim; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Monotherapy

Platform Trial Evaluating Safety and Efficacy of BI 754091 Anti- PD-1 Based Combination Therapies in PD-(L)1 naïve and PD- (L)1 Pretreated Patient Populations With Advanced/Metastatic Solid Tumours. (clinicaltrials.gov) - P2; N=260; Recruiting; Sponsor: Boehringer Ingelheim; Trial completion date: May 2021 ➔ Dec 2021; Trial primary completion date: May 2021 ➔ Dec 2021

Clinical • Combination therapy • Trial completion date • Trial primary completion date

A Study to Test Different Doses of BI 891065 Alone and in Combination With BI 754091 in Asian Patients With Different Types of Advanced Cancer (Solid Tumours) (clinicaltrials.gov) - P1; N=24; Not yet recruiting; Sponsor: Boehringer Ingelheim

Clinical • Combination therapy • Monotherapy • New P1 trial