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

Neoplasms Clinical Trial

Official title:

A Phase Ia/Ib, Open Label, Multicenter, Dose-escalation Study of BI 907828 (Brigimadlin) in Patients With Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03449381
• Other study ID #: 1403-0001
• Secondary ID: 2017-003210-95
• Status: Recruiting
• Phase: Phase 1
• Start date: May 21, 2018
• Est. completion date: April 30, 2026

Study information

• Verified date: April 2024
• Source: Boehringer Ingelheim
• Contact: Boehringer Ingelheim
• Phone: 1-800-243-0127
• Email: clintriage.rdg[@]boehringer-ingelheim.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 269
• Est. completion date: April 30, 2026
• Est. primary completion date: March 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

• Phase Ib (expansion phase) only:

• At least one target lesion that can be accurately measured per RECIST v.1.1.

• Phase Ia:

• Patient must be willing to undergo blood sampling for PK, pharmacodynamic, biomarker, and PGx analyses.

• Phase Ib:

• Patient must be willing to undergo tumor biopsy sampling for pharmacodynamic analyses and blood sampling for PK, pharmacodynamics, and biomarker analyses.

• Willingness to provide a fresh tumor tissue sample obtained after relapse/ progression during or after prior therapy. In case a fresh biopsy cannot be obtained (e.g. inaccessible lesions or patient safety concern), an archived specimen, collected before screening within 12 months of enrollment, may be submitted. If these requirements cannot be met, then the patient may be allowed to enter the study at Sponsor discretion, after agreement between the Investigator and Sponsor.

• Further inclusion criteria apply

Exclusion Criteria:

• 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.

• Further exclusion criteria apply.

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• BI 907828
Film-coated tablet

Locations

Country	Name	City	State
Belgium	Brussels - UNIV Saint-Luc	Bruxelles
Belgium	UZ Leuven	Leuven
Canada	The Ottawa Hospital	Ottawa	Ontario
Denmark	Rigshospitalet, København	København Ø
Germany	Helios Klinikum Berlin-Buch	Berlin
Germany	Universitätsmedizin Göttingen, Georg-August-Universität	Göttingen
Germany	Universitätsklinikum Köln (AöR)	Köln
Germany	Universitätsklinikum Tübingen	Tübingen
Israel	Sourasky Medical Center	Tel Aviv
Japan	National Cancer Center Hospital	Tokyo, Chuo-ku
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Poland	MED POLONIA SP Z O O, Clinical Trials Department,Poznan	Poznan
Poland	Oncology Center-Maria Sklodowska-Curie Institute	Warsaw
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Fundación Jiménez Díaz	Madrid
Spain	Hospital Clínico de Santiago	Santiago de Compostela
Sweden	Karolinska Comprehensive Cancer Center	Stockholm
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	START Midwest	Grand Rapids	Michigan
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Norton Cancer Institute, Downtown	Louisville	Kentucky
United States	University of Wisconsin	Madison	Wisconsin
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Sarcoma Oncology Center	Santa Monica	California
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Denmark,  Germany,  Israel,  Japan,  Korea, Republic of,  Poland,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase Ia- Maximum tolerated dose (MTD) based on number of patients with dose limiting toxicities (DLTs) during first treatment cycle		Up to 28 days
Primary	Phase Ib - Progression-free survival		Up to 24 months
Primary	Phase Ia - Number of patients with DLTs during first treatment cycle (21 days, Arm A; 28 days, Arm B)		Up to 28 days
Primary	Phase Ib - Number of patients with DLTs during the first treatment cycle		Up to 28 days
Secondary	Phase Ia - Cmax: Maximum measured concentration of BI 907828 in plasma		Up to 24 months
Secondary	Phase Ia - AUC0-8: Area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity		Up to 24 months
Secondary	Phase Ib - Objective response		Up to 24 months
Secondary	Phase Ib - Overall survival		Up to 24 months
Secondary	Phase Ib - Number of patients with Grade =3 treatment-related adverse events observed during the entire treatment period		Up to 24 months
Secondary	Phase Ib - Cmax: Maximum measured concentration of BI 907828 in plasma		Up to 24 months
Secondary	Phase Ib - AUC0-8: Area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity		Up to 24 months

External Links

•   Related Info