brigimadlin (BI 907828) / Boehringer Ingelheim - LARVOL DELTA

Microperfusion-Based Biomarker Analysis in Glioblastoma: Integrating Preclinical and Clinical Perspectives (SNO 2025) - "In this study, MP was used to measure the GDF-15 (24.8 kDa) levels in TP53 wild-type, MDM2-amplified GBM treated with Brigimadlin, using orthotopic mouse models...MP enabled quantification of GDF-15 dynamics in vivo, highlighting its potential in clinical settings. An investigational device exemption has been secured for an upcoming clinical trial deploying intraoperative use of cerebral microperfusion catheters."

Preclinical • Brain Cancer • Glioblastoma • Solid Tumor • GDF15 • MDM2

This Study Aims to Find the Best Dose of BI 907828 (Brigimadlin) in Patients With Different Types of Advanced Cancer (Solid Tumors) (clinicaltrials.gov) - P1 | N=266 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • Cholangiocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MDM2 • TP53

UNRESECTABLE AND METASTATIC DEDIFFERENTIATED LIPOSARCOMA (DDLPS): INSIGHTS FROM A MULTICENTER REAL-WORLD COHORT (RWC) (CTOS 2025) - "First line (1L) Tx were Doxorubicin (D) (46.5%), anthracycline-ifosfamide (AI) (21%), trabectedin (Tr) (10.3%) brigimadlin (Bg) (7.1%) and eribulin (Er) (6.5%)...Among regimens, AI and Bg had the highest OS at 3 years (55%, 64%, respectively), though no Tx sequence demonstrated statistical significance.Second line (2L) CT was given in 56% of pts: Tr (41.4%; RR: 22%), DTIC-Gemcitabine DG (19.5%; RR: 5.9%), Er (16%; RR: 14%), and D (9.2%; RR: 14%), with mPFS of 3.9m... Tx patterns in UM DDLPS remain heterogeneous with modest outcomes. AI and Bg showed OS trends, though not statistically significant due to sample size. These data underscore the need for novel Tx strategies and randomized trials to improve care."

Clinical • Metastases • Real-world • Real-world evidence • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Microperfusion-Based Biomarker Analysis in Glioblastoma: Integrating Preclinical and Clinical Perspectives (WFNOS 2025) - "In this study, MP was used to measure the GDF-15 (24.8 kDa) levels in TP53 wild-type, MDM2-amplified GBM treated with Brigimadlin, using orthotopic mouse models...MP enabled quantification of GDF-15 dynamics in vivo, highlighting its potential in clinical settings. An investigational device exemption has been secured for an upcoming clinical trial deploying intraoperative use of cerebral microperfusion catheters."

Preclinical • Brain Cancer • Glioblastoma • Solid Tumor • GDF15 • MDM2

Therapeutic Evaluation of Brigimadlin and Anti-PD-1 in a PBMC-Co-culture Model of Patient-Derived Liposarcoma Organoids (AACR-NCI-EORTC 2025) - "Treatment groups included vehicle control, Brigimadlin alone, anti-PD-1 antibody (Durvalumab) alone, and the combination therapy. This co-culture model provides a clinically relevant platform for evaluating immunotherapeutic combinations and enables the establishment of a personalized cancer model. By facilitating patient-specific drug screening, this approach has the potential to minimize the burden of ineffective treatments in liposarcoma patients."

Liposarcoma • Oncology • Sarcoma • Solid Tumor • MDM2

A Study to Test Long-term Treatment With Brigimadlin in People With Solid Tumours Who Took Part in a Previous Study With This Medicine (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Boehringer Ingelheim | N=50 ➔ 90

Enrollment change • Solid Tumor

Brightline-2: A Study to Test Whether Brigimadlin (BI 907828) Helps People With Cancer in the Biliary Tract, Pancreas, Lung or Bladder (clinicaltrials.gov) - P2 | N=99 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • Biliary Cancer • Biliary Tract Cancer • Bladder Cancer • Cholangiocarcinoma • Gallbladder Cancer • Genito-urinary Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • MDM2 • TP53

EMPIRE: Targeting MDMD and PD1 in Tumors With Tertiary Lymphoid Structures (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Institut Bergonié | N=120 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Triple Negative Breast Cancer • PD-L1 • TP53

MDM2-GPX4-ferroptosis regulatory axis exerts neurotoxic effects in intracerebral hemorrhage. (PubMed, Neural Regen Res) - "Furthermore, intracerebral hemorrhage mouse models were constructed with and without an murine double minute 2 inhibitor (brigimadlin), and behavioral assays were performed to assess the learning ability and cognitive function...This regulation promotes ferroptosis and inflammatory responses in oxygen-glucose deprivation combined with hemin-induced BV2 microglial cells, suggesting that the murine double minute 2-glutathione peroxidase 4-ferroptosis regulatory axis exerts neurotoxic effects. These findings identify glutathione peroxidase 4 as a potential gene therapy target for intracerebral hemorrhage-related brain injury."

Journal • Cerebral Hemorrhage • CNS Disorders • Gene Therapies • Hematological Disorders • Nephrology • Oncology • Solid Tumor • Targeted Protein Degradation • Vascular Neurology • Wilms Tumor • GPX4 • WT1

A Study to Determine How BI 907828 (Brigimadlin) is Taken up in the Tumor (Phase 0) and to Determine the Highest Dose of BI 907828 (Brigimadlin) That Could be Tolerated (Phase 1a) in Combination With Radiation Therapy in People With a Brain Tumor Called Glioblastoma (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • TP53

Brigimadlin (BI-907828) and napabucasin (BBI608) cooperatively trigger apoptosis in chronic lymphocytic leukemia cells by simultaneous iİnhibition of MDM2 and STAT3. (PubMed, Mol Biol Rep) - "These findings establish a mechanistic rationale for the concurrent targeting of the MDM2 and STAT3 axes and provide preclinical evidence for a promising, non-genotoxic therapeutic strategy in p53-functional CLL. A limitation of this study is the lack of in vivo validation and clinical data, which are necessary to further assess the safety, optimal dosing, and efficacy, particularly in elderly or unfit patients with limited treatment options."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CASP3 • CASP7 • CDKN1A • STAT3

Brightline-2: A Study to Test Whether Brigimadlin (BI 907828) Helps People With Cancer in the Biliary Tract, Pancreas, Lung or Bladder (clinicaltrials.gov) - P2 | N=99 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial primary completion date: Jun 2025 ➔ Oct 2025

Trial primary completion date • Biliary Cancer • Biliary Tract Cancer • Bladder Cancer • Cholangiocarcinoma • Gallbladder Cancer • Genito-urinary Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • MDM2 • TP53

A Study in People With Advanced Cancer to Test Whether the Amount of BI 907828 in the Blood is Influenced by Taking an OATP Inhibitor or a CYP3 Inhibitor (clinicaltrials.gov) - P1 | N=33 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • Oncology • Solid Tumor • TP53

A Study to Test Long-term Treatment With Brigimadlin in People With Solid Tumours Who Took Part in a Previous Study With This Medicine (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Dec 2036 ➔ Dec 2030 | Trial primary completion date: Dec 2036 ➔ Dec 2030

Trial completion date • Trial primary completion date • Solid Tumor

Brightline-2: A Study to Test Whether Brigimadlin (BI 907828) Helps People With Cancer in the Biliary Tract, Pancreas, Lung or Bladder (clinicaltrials.gov) - P2 | N=99 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Jun 2025 ➔ Oct 2025

Trial completion date • Biliary Cancer • Biliary Tract Cancer • Bladder Cancer • Cholangiocarcinoma • Gallbladder Cancer • Genito-urinary Cancer • Hepatology • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • MDM2 • TP53

The impact of therapeutic radiation on drug distribution across the blood-brain barrier in normal mouse brain and orthotopic GBM tumors. (PubMed, Neuro Oncol) - "Radiation had no meaningful impact of drug delivery into brain or brain tumors for the drugs tested."

Journal • Preclinical • Brain Cancer • CNS Disorders • Oncology • Solid Tumor

Real-World Experience Using Brigimadlin (MDM2 Inhibitor) in an Australian Sarcoma Specialist Center Compared to Pivotal Clinical Trial Results. (PubMed, Asia Pac J Clin Oncol) - No abstract available

Journal • Real-world evidence • Oncology • Sarcoma • Solid Tumor

Exposure-tumour growth inhibition modelling of brigimadlin using phase I solid tumour data to support phase II dose selection. (PubMed, Br J Clin Pharmacol) - "The developed E-TGI model predicted that higher doses of brigimadlin resulted in a substantially stronger tumour shrinkage. These results contributed to selecting 45 mg brigimadlin q3w dose as RP2D in subsequent clinical trials."

Journal • P1 data • P2 data • Liposarcoma • Oncology • Sarcoma • Solid Tumor

A Study to Test Long-term Treatment With Brigimadlin in People With Solid Tumours Who Took Part in a Previous Study With This Medicine (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor

Brightline-1: A Study to Compare Brigimadlin (BI 907828) With Doxorubicin in People With a Type of Cancer Called Dedifferentiated Liposarcoma (clinicaltrials.gov) - P2/3 | N=401 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: May 2026 ➔ Nov 2025

Trial completion date • Liposarcoma • Oncology • Sarcoma • Solid Tumor • MDM2

Targeting the MDM2-p53 pathway in dedifferentiated liposarcoma -Brigimadlin (BI-907827)- (JSMO 2025) - No abstract available

Liposarcoma • Oncology • Sarcoma • Solid Tumor

A Study to Test Long-term Treatment With Brigimadlin in People With Solid Tumours Who Took Part in a Previous Study With This Medicine (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor

A Study to Determine How BI 907828 (Brigimadlin) is Taken up in the Tumor (Phase 0) and to Determine the Highest Dose of BI 907828 (Brigimadlin) That Could be Tolerated (Phase 1a) in Combination With Radiation Therapy in People With a Brain Tumor Called Glioblastoma (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Dec 2026 ➔ Aug 2025 | Trial primary completion date: Nov 2026 ➔ Aug 2025

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • TP53

Brightline-4: A Study to Test How Well Brigimadlin is Tolerated by People With a Type of Cancer Called Dedifferentiated Liposarcoma (clinicaltrials.gov) - P3 | N=138 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Nov 2025 ➔ Jul 2025 | Trial primary completion date: Nov 2025 ➔ Jul 2025

Trial completion date • Trial primary completion date • Liposarcoma • Oncology • Sarcoma • Solid Tumor • MDM2

A Study in People With Advanced Cancer to Test Whether the Amount of BI 907828 in the Blood is Influenced by Taking an OATP Inhibitor or a CYP3 Inhibitor (clinicaltrials.gov) - P1 | N=34 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Feb 2025 ➔ Jun 2025

Trial completion date • Oncology • Solid Tumor • TP53