BI 1823911 / Boehringer Ingelheim - LARVOL DELTA

A Study to Test Different Doses of BI 1823911 Alone and Combined With Other Medicines in People With Different Types of Advanced Cancer With KRAS Mutation (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Nov 2024 ➔ Nov 2025

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

A Study to Test Different Doses of BI 1823911 Alone and Combined With Other Medicines in People With Different Types of Advanced Cancer With KRAS Mutation (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Phase classification: P1a/1b ➔ P1

Combination therapy • Metastases • Monotherapy • Phase classification • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

First-in-human, phase Ia/b, dose-escalation/expansion study of KRAS G12C inhibitor BI 1823911, as monotherapy and combined with anticancer therapies, in patients (pts) with advanced or metastatic solid tumours harbouring a KRAS G12C mutation (ESMO 2023) - P1a/1b | "Conclusions Preliminary data suggest BI 1823911 monotherapy is generally well tolerated and offers clinical activity. Recruitment is ongoing; updated data will be presented."

Clinical • Metastases • Monotherapy • P1 data • Oncology • Solid Tumor • KRAS

A Study to Test Different Doses of BI 1823911 Alone and Combined With Other Medicines in People With Different Types of Advanced Cancer With KRAS Mutation (clinicaltrials.gov) - P1a/1b | N=29 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

A Study to Test Different Doses of BI 1823911 Alone and Combined With Other Medicines in People With Different Types of Advanced Cancer With KRAS Mutation (clinicaltrials.gov) - P1a/1b | N=29 | Recruiting | Sponsor: Boehringer Ingelheim | N=72 ➔ 29 | Trial completion date: Jul 2024 ➔ Dec 2024

Enrollment change • Trial completion date • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Trial in progress: Phase 1 study of BI 1823911, an irreversible KRASG12C inhibitor targeting KRAS in its GDP-loaded state, as monotherapy and in combination with the pan-KRAS SOS1 inhibitor BI 1701963 in solid tumors expressing KRASG12C mutation (AACR 2022) - P1a/1b | "Inhibition of KRASG12C mediated signaling and the therapeutic impact in non-small cell lung cancer (NSCLC) whose tumors carry this mutation was demonstrated clinically by sotorasib and adagrasib leading to approval of sotorasib in KRASG12C mutant NSCLC...The pan-KRAS SOS1 inhibitor BI 1701963 is the first direct KRAS signaling modifier, which entered phase I clinical trials both as a monotherapy as well as in combination with KRASG12C inhibitors, MEK inhibitors and irinotecan...Primary endpoints include dose-limiting toxicities, treatment-emergent or -related adverse events. Secondary endpoints include pharmacokinetic properties of combination regimens and preliminary efficacy."

Combination therapy • Monotherapy • P1 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • KRAS

A Study to Test Different Doses of BI 1823911 Alone and Combined With Other Medicines in People With Different Types of Advanced Cancer With KRAS Mutation (clinicaltrials.gov) - P1a/1b | N=60 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Jan 2024 ➔ Jul 2024 | Trial primary completion date: Dec 2023 ➔ Jun 2024

Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

A Study to Test Different Doses of BI 1823911 Alone and Combined With Other Medicines in People With Different Types of Advanced Cancer With KRAS Mutation (clinicaltrials.gov) - P1a/1b | N=60 | Recruiting | Sponsor: Boehringer Ingelheim | N=245 ➔ 60 | Trial completion date: Oct 2024 ➔ Jan 2024 | Trial primary completion date: Oct 2024 ➔ Dec 2023

Combination therapy • Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

[VIRTUAL] Trial in Process: Phase 1 studies of BI 1701963, a SOS1::KRAS Inhibitor, in combination with MEK inhibitors, irreversible KRASG12C inhibitors or irinotecan. (AACR 2021) - "Here, we present pre-clinical data showing enhanced pathway modulation and synergistic anti-tumor effects following vertical pathway inhibition of BI 1701963 in combination with mitogen-activated protein kinase inhibitors (MEKi; trametinib and BI 3011441) or KRAS G12C inhibitors (MRTX849 and BI 1823911). Primary endpoints include dose-limiting toxicities, treatment-emergent or -related adverse events. Secondary endpoints include pharmacokinetic and pharmacodynamic properties of combination regimens and preliminary efficacy."

Combination therapy • P1 data • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • KRAS • SOS1

A Study to Test Different Doses of BI 1823911 Alone and Combined With Other Medicines in People With Different Types of Advanced Cancer With KRAS Mutation (clinicaltrials.gov) - P1a/1b; N=245; Recruiting; Sponsor: Boehringer Ingelheim; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Monotherapy • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

A Study to Test Different Doses of BI 1823911 Alone and Combined With Other Medicines in People With Different Types of Advanced Cancer With KRAS Mutation (clinicaltrials.gov) - P1a/1b; N=245; Not yet recruiting; Sponsor: Boehringer Ingelheim

Clinical • Combination therapy • Monotherapy • New P1 trial • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

[VIRTUAL] In vitro and in vivo characterization of BI 1823911 - a novel KRASG12C selective small molecule inhibitor (AACR 2021) - "Early clinical data for AMG 510 and MRTX849 revealed a response rate of 35-45% in NSCLC and of 7-17% in CRC patients. Among other MAPK and PI3K pathway inhibitors, a SOS1::KRAS inhibitor was confirmed as promising combination partner. We will show results from in vitro and in vivo combination studies in NSCLC and CRC tumor models that show deep and durable responses upon combination of BI 1823911 with SOS1::KRAS inhibitor BI 1701963 providing a strong rationale for clinical investigation of this combination."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CCND1 • DUSP6 • KRAS • SOS1

Boehringer Ingelheim and MD Anderson Expand Collaboration to Accelerate Development of KRAS and TRAILR2 Compounds in Lung Cancer (Businesswire) - "Boehringer Ingelheim and The University of Texas MD Anderson Cancer Center...announced the extension and expansion of their joint Virtual Research and Development Center (VRDC) to explore new molecules from Boehringer Ingelheim’s KRAS (Kirsten rat sarcoma) and TRAILR2 (TNF-related apoptosis-inducing ligand receptor 2) portfolios for the potential treatment of lung cancer, particularly non-small cell lung cancer....The flexible nature of the VRDC agreement allows the teams to expand their lung cancer indication programs targeting KRAS and TRAILR2, including Boehringer Ingelheim’s first-in-class SOS1::pan-KRAS inhibitor (BI 1701963), inhibitors of KRAS G12C (BI 1823911) and MEK (BI 3011441), as well as a novel undisclosed bi-specific TRAILR2 agonist."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor