brigimadlin (BI 907828) / Boehringer Ingelheim - LARVOL DELTA

Efficacy and safety of the MDM2–p53 antagonist BI 907828 in patients with advanced biliary tract cancer: Data from two phase Ia/Ib dose-escalation/expansion trials. (ASCO-GI 2023) - P1a/1b, P2a/2b | "Patients in the combination trial received escalating doses of BI 907828 and 240 mg ezabenlimab q3w (doublet); one patient also received the anti-LAG-3 antibody BI 754111 (a drug that has since been discontinued; triplet). The MDM2–p53 antagonist BI 907828 has shown a manageable safety profile and encouraging preliminary efficacy in patients with BTC, with 5 PRs and 2 SD in 8 patients. A phase IIa/IIb trial of BI 907828 (45 mg q3w) in patients with BTC is planned to start recruitment at the end of 2022 (NCT05512377). Clinical trial information: NCT03449381 and NCT03964233."

Clinical • IO biomarker • Metastases • P1 data • Ampulla of Vater Carcinoma • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MDM2 • TP53

A PHASE IA/IB, DOSE-ESCALATION/EXPANSION STUDY OF THE MDM2–P53 ANTAGONIST BI 907828 IN PATIENTS WITH SOLID TUMORS, INCLUDING ADVANCED/METASTATIC LIPOSARCOMA (CTOS 2022) - No abstract available

Clinical • P1 data • Liposarcoma • Oncology • Sarcoma • Solid Tumor

Brightline-1: phase II/III trial of the MDM2-p53 antagonist BI 907828 versus doxorubicin in patients with advanced DDLPS. (PubMed, Future Oncol) - P2/3 | "BI 907828 has shown promising activity in preclinical studies and in a phase Ia/Ib study in patients with solid tumors, particularly those with DDLPS. This manuscript describes the rationale and design of an ongoing multicenter, randomized, phase II/III trial (Brightline-1; NCT05218499) evaluating BI 907828 versus doxorubicin as first-line treatment for advanced DDLPS."

Journal • Metastases • P2/3 data • Review • Liposarcoma • Oncology • Sarcoma • Solid Tumor • MDM2

BRIGIMADLIN VERSUS STANDARD-OF-CARE DOXORUBICIN AS FIRST-LINE TREATMENT IN PATIENTS WITH ADVANCED DEDIFFERENTIATED LIPOSARCOMA (DDLPS): BRIGHTLINE-1 (CTOS 2024) - No abstract available

Clinical • Metastases • Liposarcoma • Oncology • Sarcoma • Solid Tumor

A Phase 0/Ia study of brigimadlin concentration in brain tissue and a dose escalation study of brigimadlin plus radiotherapy in patients with newly diagnosed glioblastoma (EANO 2024) - P1 | "Unbound brigimadlin concentrations in CE regions in all patients receiving the low dose of 30 mg brigimadlin exceeded the 0.5 nmol/L threshold. K p,uu in most patients was close to 1 in CE regions. Biomarker data support target engagement in brain tissue."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

BRIGHTLINE-1: When a Negative Trial Reveals Two Active Therapies. (PubMed, Clin Cancer Res) - "Although BRIGHTLINE-1 was headlined as a "negative trial," brigimadlin showed clear biological activity, with median PFS of 8.4 months, ORR of 22.3%, and translational evidence of p53 reactivation. Its failure largely reflects flawed control-arm assumptions, as doxorubicin outperformed retrospective expectations and established a new prospective benchmark in DDLPS."

Journal

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 | Terminated ➔ 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

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 | Active, not recruiting | Sponsor: Boehringer Ingelheim | N=31 ➔ 90

Enrollment change • Oncology • 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 | Trial completion date: Dec 2036 ➔ Dec 2030 | Trial primary completion date: Dec 2036 ➔ Dec 2030

Trial completion date • Trial primary completion date • 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 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 | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • 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=31 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • 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 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P2 trial • Oncology • 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=90 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting | N=31 ➔ 90

Enrollment change • Enrollment closed • Oncology • 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=90 | Recruiting | Sponsor: Boehringer Ingelheim | N=50 ➔ 90

Enrollment change • 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

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=31 | 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=400 | Completed | Sponsor: Boehringer Ingelheim | Phase classification: P2 ➔ P2/3 | Active, not recruiting ➔ Completed

Phase classification • Trial completion • Liposarcoma • Oncology • Sarcoma • Solid Tumor • MDM2

Brigimadlin Versus Doxorubicin in Advanced Dedifferentiated Liposarcoma: Efficacy, Safety and Translational Data from Brightline-1, a Randomized Phase 2/3 Trial. (PubMed, Clin Cancer Res) - P2/3 | "While brigimadlin showed activity in this patient population, the median PFS with doxorubicin was substantially longer than anticipated and the primary endpoint of PFS was not met. The safety profile of brigimadlin also did not appear to be more manageable than that of doxorubicin. The translational results will guide future clinical investigations of MDM2-p53 antagonists."

Journal • P2/3 data • Hematological Disorders • Liposarcoma • Neutropenia • Oncology • Sarcoma • Solid Tumor • Thrombocytopenia • MDM2

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 | Terminated | Sponsor: Boehringer Ingelheim | Completed ➔ Terminated; Sponsor decision

Trial termination • 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

Brightline-4: A phase 3 open-label, single-arm, multicenter study to assess the safety and efficacy of brigimadlin (BI 907828) treatment in patients with treatment-naïve or pretreated advanced dedifferentiated liposarcoma (AACR 2024) - P1, P2/3, P3 | "Secondary endpoints include objective response, progression-free survival, overall survival, duration of response, disease control and further assessment of safety. All analyses will be descriptive; no hypothesis testing is planned."

Clinical • Metastases • P3 data • Liposarcoma • Oncology • Sarcoma • Solid Tumor • MDM2

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=400 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • Liposarcoma • Oncology • Sarcoma • Solid Tumor • 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=267 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Apr 2026 ➔ Jun 2025 | Trial primary completion date: Mar 2026 ➔ Jun 2025

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

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=267 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed • Cholangiocarcinoma • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MDM2 • TP53

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=269 | Recruiting | Sponsor: Boehringer Ingelheim | Phase classification: P1a/1b ➔ P1 | N=204 ➔ 269

Enrollment change • Phase classification • Cholangiocarcinoma • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MDM2 • TP53