Cancer (solid tumors)
Conditions
Interventions
Phase Ib - Dose Expansion:
The recommended dose for expansion (RDE) of BI 907828 in combination with a
fixed dose of ezabenlimab, on Day 1 every 3 weeks, as established in Phase Ia.
The RDE will be
Sponsors
Boehringer Ingelheim
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. 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. 2. Male or female >=18 years old at the time of signature of the ICF. 3. ECOG performance status of 0 or 1. 4. Life expectancy of at least 12 weeks after the start of the treatment according to the Investigator*s judgement. 5. Patients with radiologically documented disease progression or relapse during or after all standard of care treatments. Patients who are not eligible to receive standard of care treatments, and for whom no proven treatments exist, are eligible. 6. Previous treatment with an anti-PD-1/PD-L1 mAb is allowed as long as the last administration of the anti-PD-1/PD-L1 mAb on the previous treatment occurred a minimum of 28 days prior to the first administration of study treatment. 7. Patient must be willing to participate in the blood sampling for the PK, PD, and tumor mutation analysis. 8. Adequate organ function defined as all of the following (all screening labs should be performed locally within 10 days of treatment initiation): Absolute neutrophil count >=1.5 x 10^9/L (or >= 1.5×10^3/µL or >= 1500/mm^3) Platelets >=100 x 10^9/L (or >= 100×10^3/µL or >= 100×10^3/mm^3) Hemoglobin >=8.5 g/dL or >=5.3 mmol/L (red blood cell transfusion allowed to meet eligibility criteria) or >= 85 g/L Total bilirubin 1.5 x ULN and estimated glomerular filtration rate (eGFR) >50 mL/min (assessed by Chronic Kidney Disease Epidemiology [CKDEPI] Collaboration equation); confirmation of eGFR is only required when creatinine is >1.5 X ULN International Normalised Ratio (INR) or Prothrombin Time (PT). Activated Partial Thromboplastin Time (aPTT) <=1.5 x institutional ULN. Patients taking low dose warfarin must have their INR followed closely and according to institutional guidelines. 9. Women of childbearing potential (WOCBP), and men able to father a child must be ready and able to use two medically acceptable methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly beginning at screening, during trial participation and until certain time has passed after the last administration of trial medication: - Women: 6 months and 12 days after end of BI 907828; 6 months after end of ezabenlimab. - Men: 102 days after end of BI 907828; 6 months after end of ezabenlimab. A list of contraception methods meeting these criteria is provided in the patient information. Inclusion criteria 10-14 are only applicable to Phase I a. The following inclusion criteria are only applicable to Phase I b: 15. At least one target lesion that can be accurately measured per RECIST 1.1. In patients who only have one target lesion, the baseline imaging must be performed at least two weeks after any biopsy of the target lesion. 16. Patients with TP53 wild-type status confirmed on tumor tissue. 17. Provision of fresh tissue biopsy at screening (may be omitted if patient has archival t
Exclusion criteria
Exclusion criteria: Patients must not enter the trial if any of the following exclusion criteria are fulfilled: 1. Previous administration of BI 907828 or any other MDM2-p53 or MDMX (MDM4)-p53 antagonist. 2. In Phase Ib (expansion phase) and Phase Ia expansion cohort only: a documented aminoacid altering mutation in TP53 occurring in the patient*s tumor. 3. Symptomatic brain metastases. Note: Patients with previously treated brain metastases may participate but treated lesions should not be used as target lesions. 4. Exclusion criterion 4 is not applicable for patients enrolled after protocol version 4 is approved. 5. Active bleeding, significant risk of haemorrhage (e.g. previous severe gastrointestinal bleeding, previous haemorrhagic stroke at any time), or current bleeding disorder (e.g. haemophilia, von Willebrand disease). 6. 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). 7. 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. 8. Patients who must or wish to continue the intake of restricted medications (see Section 4.2.2.1) or any drug considered likely to interfere with the safe conduct of the trial. 9. Currently enrolled in another investigational device or drug trial, or less than 4 weeks since receiving other investigational treatments. Patients who are in follow-up/observation for another clinical trial are eligible. 10. Exclusion criterion 10 is not applicable for patients enrolled after protocol version 4 is approved. 11. Patients who have not recovered from all clinically significant adverse events from their most recent therapy or intervention prior to study enrolment. 12. Known history of human immunodeficiency virus (HIV) infection. 13. Any of the following known laboratory evidence of hepatitis virus infection: o Positive results of hepatitis B surface (HBs) antigen o Presence of HBc antibody together with HBV-DNA o Presence of hepatitis C RNA 14. Known hypersensitivity to the trial drugs or their excipients. 15. Serious concomitant disease or medical condition affecting compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug, such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the Investigator, would make the patient inappropriate for entry into the trial. 16. Chronic alcohol or drug abuse or any condition that, in the Investigator*s opinion, makes them an unreliable trial patient or unlikely to complete the trial. 17. Women who are pregnant, nursing, or who plan to become pregnant while in the trial; female patients who do not agree to the interruption of breast feeding from the start of study treatment until 6 months and 12 days after last dose of study treatment. 18. History of (including current) interstitial lung disease or pneumon
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase Ib: - Objective response (OR), as assessed by the investigator according to RECIST v. 1.1, measured separately for each cohort. OR is defined as best overall response of confirmed complete response (CR) and/or confirmed partial response (PR) from the start of treatment until the earliest of disease progression (PD), death or last evaluable tumor assessment, and before start of subsequent anti-cancer therapy. - Progression-Free Survival defined as the time from the start of treatment until the earliest of PD or death. Determination of progression is based on objective evaluation per RECIST v. 1.1 by investigators. | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase Ib: - Objective Response (OR) according to iRECIST as assessed by the investigator. - Disease control (DC) according to RECIST 1.1 and iRECIST as assessed by the investigator. - Overall survival (OS): defined as the time from start of treatment until death from any cause. - Number of patients with DLTs observed during the entire treatment period for each combination treatment. | — |
Countries
Netherlands
Outcome results
None listed