This Study Aims to Find the Best Dose of BI 907828 (Brigimadlin) in Patients With Different Types of Advanced Cancer (Solid Tumors)

NCT03449381 | Completed Phase 1 FDA Drug

• 2 other identifiers: 1403-00012017-003210-95
• Study Type: interventional
• Target: 266
• Locations: 11 countries
• Sites: 27

Brief Summary

This study is open to adults with different types of advanced cancer (solid tumors). The purpose of this study is to find out the most suitable dose of BI 907828 (brigimadlin) the participants can tolerate. The most suitable dose is used in the second part to find out whether brigimadlin makes tumors shrink. In this study, brigimadlin is given to humans for the first time. Brigimadlin is a so-called MDM2 inhibitor that is being developed to treat cancer. Brigimadlin is taken as a tablet. Participants either take a dose of brigimadlin on one day every 3 weeks or on two days every 4 weeks. The participants are in the study for as long as they benefit from and can tolerate treatment. The doctors regularly check the participants' general health during the study.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (4)

• Phase Ia- Maximum tolerated dose (MTD) based on number of patients with dose limiting toxicities (DLTs) during first treatment cycle

  Up to 28 days

• Phase Ib - Progression-free survival

  Up to 24 months

• Phase Ia - Number of patients with DLTs during first treatment cycle (21 days, Arm A; 28 days, Arm B)

  Up to 28 days

• Phase Ib - Number of patients with DLTs during the first treatment cycle

  Up to 28 days

Secondary Outcomes (7)

• Phase Ia - Cmax: Maximum measured concentration of BI 907828 in plasma

  Up to 24 months

• Phase Ia - AUC0-∞: Area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity

  Up to 24 months

• Phase Ib - Objective response

  Up to 24 months

• Phase Ib - Overall survival

  Up to 24 months

• Phase Ib - Number of patients with Grade ≥3 treatment-related adverse events observed during the entire treatment period

  Up to 24 months

Study Arms (2)

Dose Escalation

EXPERIMENTAL

Drug: BI 907828

Dose Expansion

EXPERIMENTAL

Drug: BI 907828

Interventions

BI 907828 DRUG

Film-coated tablet

Also known as: brigimadlin

Dose Escalation; Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated, written informed consent form ICF in accordance with ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or analyses.
• Pathologically documented, advanced solid tumors.
• Patients fulfilling one or more of the following criteria:
• Radiologically documented disease progression or relapse
• Patients who are not eligible to receive standard of care treatments, and for whom no proven treatments exist.
• Patients with MDM2 amplified sarcomas who require first line treatment (for Ph Ib/dose expansion - Cohort 1 only).
• Patients with MDM2 amplified sarcomas may fulfil any one of the above three criteria to be considered eligible.
• Phase Ia (dose escalation) only:
• Patient has a tumor with either a known TP53 wild type status, or unknown TP53 status, and regardless of MDM2 amplification status, at the time of study entry.
• Phase Ib (expansion phase) only:
• Cohort 1: TP53 wt and MDM2-amplified sarcoma with advanced/metastatic disease at any line of therapy. If TP53 status is not available during screening, the patient may be included with unknown TP53 status if a tissue sample is submitted for central laboratory assessment. If TP53 status cannot be evaluated, the patient may be included if agreed between the Investigator and Sponsor.
• Cohort 2: TP53 wt and MDM2- amplified NSCLC, urothelial, gastric, biliary tract (including cholangiocarcinoma, intra- and extrahepatic biliary tree, gall blander and ampulla of vater) or pancreatic solidPDAC tumors who have had at least one previous line of therapy for advanced/metastatic disease. If TP53 status cannot be evaluated the patient may be included if agreed between the Investigator and Sponsor
• Phase Ia (dose escalation) only:
• Patient with either measurable or non-measurable disease.
• Non-evaluable disease allowed.

You may not qualify if:

• Previous administration of BI 907828 (brigimadlin) or any other MDM2-p53 or MDMX (MDM4)-p53 antagonist.
• Known TP53 mutant tumor.
• Symptomatic metastases from non-brain tumors. Note: Patients with previously treated brain metastases may participate provided they are stable, without evidence of progression by imaging (using the identical imaging modality for each assessment, either MRI or computed tomography (CT) scan), for at least four weeks prior to the first dose of trial treatment, and any neurologic symptoms have returned to baseline; have no evidence of new or enlarging brain metastases. Patients on corticosteroids must have a stable dose for at least 5 days prior to baseline MRI.
• Patients with history of bleeding diathesis.
• Major surgery (major according to the Investigator's assessment) performed within 12 weeks prior to start of study treatment, or planned within 12 months after screening (e.g. hip replacement).
• Any other documented active or suspected malignancy or history of malignancy within 3 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix, or other local tumors considered cured by local treatment.
• Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (27)

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06511, United States

Location

Florida Cancer Specialists-Sarasota-61670

Sarasota, Florida, 34232, United States

Location

Norton Cancer Institute, Downtown

Louisville, Kentucky, 40202, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Rigshospitalet, København

København Ø, 2100, Denmark

Location

Helios Klinikum Berlin-Buch

Berlin, 13125, Germany

Location

Universitätsklinikum Köln (AöR)

Cologne, 50937, Germany

Location

Universitätsmedizin Göttingen, Georg-August-Universität

Göttingen, 37075, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

National Cancer Center Hospital

Tokyo, Chuo-ku, 104-0045, Japan

Location

MED POLONIA SP Z O O, Clinical Trials Department,Poznan

Poznan, 60-693, Poland

Location

Oncology Center-Maria Sklodowska-Curie Institute

Warsaw, 02-781, Poland

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Clínico de Santiago

Santiago de Compostela, 15706, Spain

Location

Karolinska Comprehensive Cancer Center

Stockholm, 171 76, Sweden

Location

Related Publications (1)

• LoRusso P, Yamamoto N, Patel MR, Laurie SA, Bauer TM, Geng J, Davenport T, Teufel M, Li J, Lahmar M, Gounder MM. The MDM2-p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced or Metastatic Solid Tumors: Results of a Phase Ia, First-in-Human, Dose-Escalation Study. Cancer Discov. 2023 Aug 4;13(8):1802-1813. doi: 10.1158/2159-8290.CD-23-0153.

  PMID: 37269344 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Neoplasms

Interventions

brigimadlin

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2018
• First Posted: February 28, 2018
• Study Start: June 20, 2018
• Primary Completion: November 13, 2025
• Study Completion: November 13, 2025
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
• Access Criteria: For study documents - upon signing of a "Document Sharing Agreement". For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Locations

DK (1); SE (1); DE (4); JP (1); PL (2); KR (1); US (9); IL (1); ES (4); CA (1); BE (2)