A phase Ia/Ib, open label, multicenter, dose-escalation study of BI 907828 in patients with advanced or metastatic solid tumors

Cancer Categories

Gastrointestinal (GI),Genitourinary (GU),Lung,Sarcoma

Karmanos Trial ID

2022-086

NCT ID

NCT03449381

Age Group

Adult

Scope

National

Phase

Phase I

Principal Investigator

Anthony
Shields, M.D., Ph.D.
Oncology - Medical View Profile

Objective:

Phase Ia – Dose escalation

Primary Objectives:

The main objective of the dose-escalation part of the trial is to determine the maximum tolerated dose (MTD), based on the frequency of patients experiencing dose limiting toxicities (DLT) during the first treatment cycle, and the recommended dose for expansion (RDE) of BI 907828 monotherapy, and to evaluate its safety and tolerability, by monitoring the occurrence and severity of adverse events (AEs), in two different schedules (Arm A with one single dose every 21 days, Arm B with one single dose on Days 1 and 8, every 28 days).

Secondary Objectives:

The determination of the pharmacokinetic (PK) profile of BI 907828 monotherapy, and the preliminary assessment of anti-tumor activity in patients with advanced or metastatic solid tumors.

Phase Ib – Dose expansion

Primary Objectives:

In dose expansion, the main objectives of Cohort 1 and Cohort 2 are to assess efficacy, and to further assess the safety and PK profiles of BI 907828 at the RDE, and to determine the RP2D of BI 907828 for TP53 wt and MDM2 amplified sarcomas, NSCLC, urothelial, gastric, biliary tract, PDAC and other tumor types.

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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.

Locations

Karmanos Cancer Institute - Detroit Headquarters

4100 John R
Detroit, MI 48201
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Phone: 800-527-6266

Karmanos Cancer Institute at Weisberg Cancer Center - Farmington Hills

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices