NeoplasmsPhase 1NCT03166631
A Trial to Find the Safe Dose for BI 891065 Alone and in Combination With BI 754091 in Patients With Incurable Tumours or Tumours That Have Spread
A Phase 1 study testing BI 891065 and BI 754091 in people with Neoplasms and Neoplasm Metastasis, run by Boehringer Ingelheim at 3 sites in United States.
Trial summary
The main objective of the dose-escalation parts of the trial is to determine the maximum tolerated dose (MTD), based on the frequency of patients experiencing dose-limiting toxicities (DLTs), and/or the recommended dose for further development of BI 891065 monotherapy as well as of BI 891065 in combination with BI… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Neoplasm Metastasis, Carcinoma, Non-Small-Cell Lung
- What is being tested?
- BI 891065 and BI 754091
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 3 sitesUnited States
- Study dates
- 8 Sep 2017to 28 Oct 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated, written informed consent form (ICF) in accordance with International Conference of Harmonization-Good Clinical Practice (ICH-GCP) and local legislation prior to any trial-specific procedures, sampling, or analyses
- Patients ≥18 years-of-age at the time of signature of the ICF
- Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control (that result in a low failure rate of less than 1% per year when used consistently and correctly)during trial participation and for at least 6 months after the last administration of trial medication. A list of contraception methods meeting these criteria is provided in the patient information.
- Eastern Cooperative Oncology Group (ECOG) score: 0 or 1
- Life expectancy of at least 12 weeks after the start of the treatment according to the Investigator's judgement
- For Parts A and B: Patients with a confirmed diagnosis of advanced, unresectable and/or metastatic solid tumours, who have failed standard treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to standard therapies. Measurable lesions according to RECIST Version 1.1 must be present. Eligibility is limited to the following tumour subtypes in Part B: bladder, colon, breast, Non-small cell lung cancer (NSCLC), ovarian, pancreatic, renal, esophagogastric, sarcoma, prostate, and melanoma.
- For Parts B and C: Patients must have measurable disease per RECIST v1.1, must have at least 1 tumour lesion amenable to biopsy, and must be willing to undergo a biopsy prior to first treatment and another biopsy while on therapy unless clinically contraindicated.
- For Part C: Patients with metastatic NSCLC who developed disease progression (per RECIST v1.1) after the first scan (where SD, Partial Response (PR), or Complete Response (CR) was demonstrated at the first scan), and require new anti-cancer therapy after first line treatment with an anti programmed cell death protein 1 (PD-1)/anti programmed cell death ligand 1 (PD-L1) monoclonal antibody (mAb) (given either as single agent therapy or in combination with a platinum-based chemotherapy regimen).
Who cannot join
- Major surgery (major according to the Investigator's and/or Medical Monitor's assessment) performed within 12 weeks prior to randomization or planned within 12 months after screening (e.g., hip replacement)
- Presence of other active invasive cancers other than the one treated in this trial within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin, or in situ carcinoma of uterine cervix, or other local tumours 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
- Previous administration of BI 891065 or BI 754091
- Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s), or receiving other investigational treatments.
- Patients who have been treated with any other anticancer drug within 4 weeks or within 5 half-life periods (whichever come earlier) prior to first administration of BI 891065. At least 7 days must have elapsed between the last dose of such agent and the first dose of study drug.
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- Persistent toxicity from previous treatments that has not resolved to ≤ Grade 1 (except for alopecia and Grade 2 neuropathy due to prior platinum-based therapy)
- Active, known or suspected autoimmune disease except vitiligo or resolved asthma/atopy
- Interstitial lung disease
- Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTcF) >470 msec
- Any clinically important abnormalities (as assessed by the investigator) in rhythm, conduction, or morphology of resting Electrocardiograms (ECGs), e.g., complete left bundle branch block, third degree heart block
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age, or any concomitant medication with known or possible risk of QT interval prolongation
- Patients with an ejection fraction (EF) <55% or the lower limit of normal of the institutional standard will be excluded. Only in cases where the Investigator (or the treating physician or both) suspects cardiac disease with negative effect on the EF, will the EF be measured during screening using an appropriate method according to local standards to confirm eligibility (e.g., echocardiogram [ECHO], multi-gated acquisition scan [MUGA]). A historic measurement of EF no older than 6 months prior to first administration of study drug can be accepted provided that there is clinical evidence that the EF value has not worsened since this measurement in the opinion of the Investigator or of the treating physician or both.
- Out of range laboratory values are defined as:
- Alanine transaminase (ALT) and aspartate amino transferase (AST) >3 times the Upper limit of normal (ULN) if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
- Total bilirubin >1.5 times ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin >3.0 times ULN or direct bilirubin >1.5 times ULN
- Human immunodeficiency virus (HIV) infection, acute or chronic viral hepatitis
- Known hypersensitivity to the trial drugs or their excipients
- 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 cardiac, 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 and/or Medical Monitor would make the patient inappropriate for entry into the trial.
- Chronic alcohol or drug abuse or any condition that, in the Investigator's and/or Medical Monitor's opinion, makes them an unreliable trial patient or unlikely to complete the trial
- Women who are pregnant, nursing, or who plan to become pregnant while in the trial and for at least 6 months after the last administration of trial medication.
- Men who plan to father a child while in the trial and for at least 6 months after the last administration of trial medication.
- Known presence of symptomatic central nervous system (CNS) metastases, unless asymptomatic and off corticosteroids and/or anti-convulsant therapy for at least 2 weeks prior start of treatment. Patients with asymptomatic CNS metastases may be enrolled following a 2-week washout period.
- Patients receiving systemic treatment with any immunosuppressive medication within 1 week prior treatment start (steroids of max. 10 mg prednisolone equivalent per day are allowed, topical and inhaled steroids are not considered as immunosuppressive).
- For Parts A and B: Patients with known epidermal growth factor receptor (EGFR), known anaplastic lymphoma kinase (ALK), or known ROS Proto-Oncogene 1 (ROS1) genomic tumour aberrations, unless disease has progressed following available EGFR or ALK targeted therapy (including osimertinib for EGFR T790M-mutated NSCLC)
- Out of range lab values as defined:
- Absolute neutrophil count (ANC) <1.5 x 109/L (<1500/mm3)
- Platelet (PLT) count <100 x 109/L
- Haemoglobin <90 g/L (<9 g/dL)
- -- Creatinine >1.5 times ULN (patients may enter if creatinine is >1.5 x ULN and estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2) (Chronic Kidney Disease Epidemiology [CKD-EPI] Collaboration equation); confirmation of eGRF is only required when creatinine is >1.5 X ULN.
- For Part C: Patients with EGFR, ALK, or (if known) ROS1 genomic tumor aberrations
- For Part C: Patients with any CTLA-4 therapy
- For Part C: One or more lines of anti-cancer therapy between previous anti-PD-1/anti-PDL1 mAb therapy and study entry.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Froedtert and The Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Florida Cancer Specialists
Sarasota, Florida, 34232
About this study
Official title: An Open-label Phase I Dose Finding Trial With BI 891065 Alone and in Combination With BI 754091 to Characterise Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy in Patients With Advanced and/or Metastatic Malignancies
The main objective of the dose-escalation parts of the trial is to determine the maximum tolerated dose (MTD), based on the frequency of patients experiencing dose-limiting toxicities (DLTs), and/or the recommended dose for further development of BI 891065 monotherapy as well as of BI 891065 in combination with BI 754091, and to evaluate its safety and tolerability by monitoring the occurrence and severity of adverse events (AEs).
Secondary objectives are the determination of the pharmacokinetic (PK) profile of BI 891065 monotherapy as well as of BI 891065 in combination with BI 754091, and the preliminary assessment of anti-tumour activity.
- Being tested
- BI 891065, BI 754091
- Medical subject headings
- Neoplasms, Neoplasm Metastasis, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BI 891065Drug
Part A, Part B
BI 754091Drug
Part B
| Study group | Role | What they receive |
|---|---|---|
| Part A: 5 mg BI 891065 | Experimental | BI 891065 alone Receives: Drug: BI 891065 |
| Part A: 15 mg BI 891065 | Experimental | BI 891065 alone Receives: Drug: BI 891065 |
| Part A: 25 mg BI 891065 | Experimental | BI 891065 alone Receives: Drug: BI 891065 |
| Part A: 50 mg BI 891065 | Experimental | BI 891065 alone Receives: Drug: BI 891065 |
| Part A: 100 mg BI 891065 | Experimental | BI 891065 alone Receives: Drug: BI 891065 |
| Part A: 200 mg BI 891065 | Experimental | BI 891065 alone Receives: Drug: BI 891065 |
| Part A: 400 mg BI 981065 | Experimental | BI 891065 alone Receives: Drug: BI 891065 |
| Part B: 50 mg BI 891065 QD + 240 mg BI 754091 | Experimental | BI 891065 in combination with BI 754091 Receives: Drug: BI 891065; Drug: BI 754091 |
| Part B: 200 mg BI 891065 QD + 240 mg BI 754091 | Experimental | BI 891065 in combination with BI 754091 Receives: Drug: BI 891065; Drug: BI 754091 |
| Part B: 400 mg BI 891065 QD + 240 mg BI 754091 | Experimental | BI 891065 in combination with BI 754091 Receives: Drug: BI 754091 |
| Part B: 200 mg BI 981065 BID + 240 mg BI 754091 | Experimental | BI 891065 in combination with BI 754091 Receives: Drug: BI 891065; Drug: BI 754091 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A - Maximum Tolerated Dose (MTD) of BI 891065
Maximum tolerated dose (MTD) defined as the highest dose with less than 25% risk of the true Dose-limiting toxicity (DLT) rate being above 33% during the MTD evaluation period.
Measured: First treatment cycle (MTD evaluation period), up to 21 days.
Part A - Number of Patients With Dose-limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period
DLT is defined as:
Hematologic toxicities for patients with solid tumors: Any Grade 5 toxicity; Neutropenia ≥Grade 4 lasting for >5 days; Febrile neutropenia of any duration; Neutropenia Grade 3 with documented infection; Grade thrombocytopenia 4, or Grade 3 with bleeding or require platelet transfusion; Grade 4 anemia unexplained by underlying disease.
Non-hematological toxicities: AST or ALT >3xULN and concurrent total bilirubin >2xULN without initial findings of cholestasis; ≥Grade 4 AST or ALT; Any ≥Grade 3 non-hematologic toxicity with some exceptions listed in protocol; Any Grade 2 pneumonitis; Any Grade 2 related uveitis, eye pain, or blurred vision that does not respond to topical therapy and does not improve to Grade 1 severity within 2 weeks or requires systemic treatment; Any treatment-related ≥Grade 2 toxicity that persists and results in an inability to administer BI 754091 on Cycle 2 Day 1.
Measured: First treatment cycle (MTD evaluation period), up to 21 days.
Part B: Maximum Tolerated Dose (MTD) of BI 891065 in Combination With Ezabenlimab
Maximum tolerated dose (MTD) of BI 891065 in combination with ezabenlimab, defined as the highest dose with less than 25% risk of the true Dose-limiting toxicity (DLT) rate being above 33% during the MTD evaluation period.
Measured: First treatment cycle (MTD evaluation period), up to 21 days.
Part B: Number of Patients With Dose-limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period
DLT is defined as:
Hematologic toxicities for patients with solid tumors: Any Grade 5 toxicity; Neutropenia ≥Grade 4 lasting for >5 days; Febrile neutropenia of any duration; Neutropenia Grade 3 with documented infection; Grade thrombocytopenia 4, or Grade 3 with bleeding or require platelet transfusion; Grade 4 anemia unexplained by underlying disease.
Non-hematological toxicities: AST or ALT >3xULN and concurrent total bilirubin >2xULN without initial findings of cholestasis; ≥Grade 4 AST or ALT; Any ≥Grade 3 non-hematologic toxicity with some exceptions listed in protocol; Any Grade 2 pneumonitis; Any Grade 2 related uveitis, eye pain, or blurred vision that does not respond to topical therapy and does not improve to Grade 1 severity within 2 weeks or requires systemic treatment; Any treatment-related ≥Grade 2 toxicity that persists and results in an inability to administer BI 754091 on Cycle 2 Day 1.
Measured: First treatment cycle (MTD evaluation period), up to 21 days.
Secondary outcomes (12)
Part A: Number of Patients With Dose-limiting Toxicities (DLT) During the Entire On-treatment Period
DLT is defined as:
Hematologic toxicities for patients with solid tumors: Any Grade 5 toxicity; Neutropenia ≥Grade 4 lasting for >5 days; Febrile neutropenia of any duration; Neutropenia Grade 3 with documented infection; Grade thrombocytopenia 4, or Grade 3 with bleeding or require platelet transfusion; Grade 4 anemia unexplained by underlying disease.
Non-hematological toxicities: AST or ALT >3xULN and concurrent total bilirubin >2xULN without initial findings of cholestasis; ≥Grade 4 AST or ALT; Any ≥Grade 3 non-hematologic toxicity with some exceptions listed in protocol; Any Grade 2 pneumonitis; Any Grade 2 related uveitis, eye pain, or blurred vision that does not respond to topical therapy and does not improve to Grade 1 severity within 2 weeks or requires systemic treatment; Any treatment-related ≥Grade 2 toxicity that persists and results in an inability to administer BI 754091 on Cycle 2 Day 1.
Measured: From first drug administration until last drug administration plus residual effect period of 30 days, up to 282 days.
Part A: Number of Patients With Objective Response (OR)
OR based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, defined as the best overall response of complete response (CR) and partial response (PR), where the best overall response is the best time point response recorded from the first administration of study medication until the end of treatment Number of patients with objective response is reported.
Measured: Up to 252 days.
Part A: Maximum Measured Plasma Concentration of BI 891065 at Steady State (Cmax,ss)
Maximum measured plasma concentration at steady state (cmax,ss) during the first treatment cycle.
Timeframe description:
*: Timepoint measured only for dose group 5 mg, 15 mg, 25 mg, and 50 mg.
**: Timepoint measured only for dose group 50 mg, 100 mg, 200 mg and 400 mg.
Measured: Just before drug intake and 0.5**, 1, 2, 3, 4*, 5, 6, 7, 8, 10**, 12*, 24, 36, 47.917, 167.917, 263.917, 335.917, 336.5**, 337, 338, 339, 340*, 341, 342, 343, 344, 346**, 348*, 359.917 hours after drug administration on day 1.
Part A: Area Under the Concentration Time Curve of BI 891065 Over a Dosing Interval at Steady State (AUCtau,ss)
Area under the concentration time curve of BI 891065 over a dosing interval at steady state (AUCtau,ss).
Timeframe description:
*: Timepoint measured only for dose group 5 mg, 15 mg, 25 mg, and 50 mg.
**: Timepoint measured only for dose group 50 mg, 100 mg, 200 mg and 400 mg.
Measured: Just before drug intake and 0.5**, 1, 2, 3, 4*, 5, 6, 7, 8, 10**, 12*, 24, 36, 47.917, 167.917, 263.917, 335.917, 336.5**, 337, 338, 339, 340*, 341, 342, 343, 344, 346**, 348*, 359.917 hours after drug administration on day 1.
Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of BI 891065 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) in the first treatment cycle.
Timeframe description:
*: Timepoint measured only for dose group 5 mg, 15 mg, 25 mg, and 50 mg.
**: Timepoint measured only for dose group 50 mg, 100 mg, 200 mg and 400 mg.
Measured: Just before drug intake and 0.5**, 1, 2, 3, 4*, 5, 6, 7, 8, 10**, 12*, 24, 36, 47.917, 167.917, 263.917, 335.917, 336.5**, 337, 338, 339, 340*, 341, 342, 343, 344, 346**, 348*, 359.917 hours after drug administration on day 1.
Part B: Number of Patients With Dose-limiting Toxicities (DLTs) Observed During the Entire Treatment Period
DLT is defined as:
Hematologic toxicities for patients with solid tumors: Any Grade 5 toxicity; Neutropenia ≥Grade 4 lasting for >5 days; Febrile neutropenia of any duration; Neutropenia Grade 3 with documented infection; Grade thrombocytopenia 4, or Grade 3 with bleeding or require platelet transfusion; Grade 4 anemia unexplained by underlying disease.
Non-hematological toxicities: AST or ALT >3xULN and concurrent total bilirubin >2xULN without initial findings of cholestasis; ≥Grade 4 AST or ALT; Any ≥Grade 3 non-hematologic toxicity with some exceptions listed in protocol; Any Grade 2 pneumonitis; Any Grade 2 related uveitis, eye pain, or blurred vision that does not respond to topical therapy and does not improve to Grade 1 severity within 2 weeks or requires systemic treatment; Any treatment-related ≥Grade 2 toxicity that persists and results in an inability to administer BI 754091 on Cycle 2 Day 1.
Measured: From first drug administration until last drug administration plus residual effect period of 30 days, up to 386 days.
Part B: Number of Patients With Objective Response (OR)
OR based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, defined as the best overall response of complete response (CR) and partial response (PR), where the best overall response is the best time point response recorded from the first administration of study medication until the end of treatment. Number of patients with objective response is reported.
Measured: Up to 356 days.
Part B: Area Under the Concentration-time Curve of BI 891065 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of BI 891065 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) in the first treatment cycle.
Measured: At 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 336.5, 337, 338, 339, 341, 342, 343, 344, 346, 359.5, 360.5, 361, 362, 363, 365, 366, 367, 368, 370 and 383.917 hours after intake of BI 891065 at day 1, cycle 1.
Part B: Area Under the Concentration Time Curve of BI 891065 Over a Dosing Interval at Steady State (AUCtau,ss)
Area under the concentration time curve of BI 891065 over a dosing interval at steady state (AUCtau,ss) in the first treatment cycle.
Measured: At 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 336.5, 337, 338, 339, 341, 342, 343, 344, 346, 359.5, 360.5, 361, 362, 363, 365, 366, 367, 368, 370 and 383.917 hours after intake of BI 891065 at day 1, cycle 1.
Part B: Maximum Measured Plasma Concentration of BI 891065 at Steady State (Cmax,ss)
Maximum measured plasma concentration of BI 891065 at steady state (Cmax,ss) in the first treatment cycle.
Measured: At 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 336.5, 337, 338, 339, 341, 342, 343, 344, 346, 359.5, 360.5, 361, 362, 363, 365, 366, 367, 368, 370 and 383.917 hours after intake of BI 891065 at day 1, cycle 1.
Part B: Maximum Measured Plasma Concentration (Cmax) of BI 754091 in the First Treatment Cycle
Maximum measured plasma concentration (Cmax) of BI 754091 in the first treatment cycle.
Results are reported for the overall group only since dose level of BI 754091 is fixed in this trial.
Measured: Predose and 1, 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 359.5, 383.917, 504, 998 and 999 hours after intake of BI 754091 at day 1, cycle 1.
Part B: Area Under the Concentration-time Curve of BI 754091 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of BI 754091 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) in the first treatment cycle.
Results are reported for the overall group only since dose level of BI 754091 is fixed in this trial.
Measured: Predose and 1, 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 359.5, 383.917, 504, 998 and 999 hours after intake of BI 754091 at day 1, cycle 1.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2017
- Study start8 Sep 2017
- Primary completion15 Sep 2020
- Study completion28 Oct 2020
Why it stopped: Not due to safety reasons.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03166631
- Sponsor's protocol ID
- 1379-0001
- Other IDs
- 2017-000465-74, 2017
- Status last verified
- Sep 2024
- First submitted
- 23 May 2017
- Last updated
- 19 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Patel MR, Hamilton EP, George B, Kretschmar G, Harada A, Graeser R, Eleftheraki A, Tachibana Y, Yamamoto N. The Second Mitochondria-Derived Activator of Caspases Mimetic BI 891065 in Patients With Advanced Solid Tumors: Results From Two Phase I Studies. Cancer Med. 2025 Dec;14(24):e71451. doi: 10.1002/cam4.71451.
PubMed 41408891
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Phase I Dose Finding Trial With BI 891065 Alone and in Combination With BI 754091 to Characterise Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy in Patients With Advanced and/or Metastatic Malignancies
- ClinicalTrials.gov ID
- NCT03166631
- Acronym / sponsor ID
- 1379-0001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Not due to safety reasons.
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 8 Sep 2017 (actual)
- Primary completion
- 15 Sep 2020 (actual)
- Study completion
- 28 Oct 2020 (actual)
- First posted
- 25 May 2017 (actual)
- Results
- Posted 19 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main objective of the dose-escalation parts of the trial is to determine the maximum tolerated dose (MTD), based on the frequency of patients experiencing dose-limiting toxicities (DLTs), and/or the recommended dose for further development of BI 891065 monotherapy as well as of BI 891065 in combination with BI 754091, and to evaluate its safety and tolerability by monitoring the occurrence and severity of adverse events (AEs).
Secondary objectives are the determination of the pharmacokinetic (PK) profile of BI 891065 monotherapy as well as of BI 891065 in combination with BI 754091, and the preliminary assessment of anti-tumour activity.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| Part A: 5 mg BI 891065 | Experimental | Drug: BI 891065BI 891065 alone |
| Part A: 15 mg BI 891065 | Experimental | Drug: BI 891065BI 891065 alone |
| Part A: 25 mg BI 891065 | Experimental | Drug: BI 891065BI 891065 alone |
| Part A: 50 mg BI 891065 | Experimental | Drug: BI 891065BI 891065 alone |
| Part A: 100 mg BI 891065 | Experimental | Drug: BI 891065BI 891065 alone |
| Part A: 200 mg BI 891065 | Experimental | Drug: BI 891065BI 891065 alone |
| Part A: 400 mg BI 981065 | Experimental | Drug: BI 891065BI 891065 alone |
| Part B: 50 mg BI 891065 QD + 240 mg BI 754091 | Experimental | Drug: BI 891065, Drug: BI 754091BI 891065 in combination with BI 754091 |
| Part B: 200 mg BI 891065 QD + 240 mg BI 754091 | Experimental | Drug: BI 891065, Drug: BI 754091BI 891065 in combination with BI 754091 |
| Part B: 400 mg BI 891065 QD + 240 mg BI 754091 | Experimental | Drug: BI 754091BI 891065 in combination with BI 754091 |
| Part B: 200 mg BI 981065 BID + 240 mg BI 754091 | Experimental | Drug: BI 891065, Drug: BI 754091BI 891065 in combination with BI 754091 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Provision of signed and dated, written informed consent form (ICF) in accordance with International Conference of Harmonization-Good Clinical Practice (ICH-GCP) and local legislation prior to any trial-specific procedures, sampling, or analyses
- Patients ≥18 years-of-age at the time of signature of the ICF
- Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control (that result in a low failure rate of less than 1% per year when used consistently and correctly)during trial participation and for at least 6 months after the last administration of trial medication. A list of contraception methods meeting these criteria is provided in the patient information.
- Eastern Cooperative Oncology Group (ECOG) score: 0 or 1
- Life expectancy of at least 12 weeks after the start of the treatment according to the Investigator's judgement
Key exclusion criteria (34 listed)
- Major surgery (major according to the Investigator's and/or Medical Monitor's assessment) performed within 12 weeks prior to randomization or planned within 12 months after screening (e.g., hip replacement)
- Presence of other active invasive cancers other than the one treated in this trial within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin, or in situ carcinoma of uterine cervix, or other local tumours 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
- Previous administration of BI 891065 or BI 754091
- Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s), or receiving other investigational treatments.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BI 891065Part A, Part B | Drug | Part A: 100 mg BI 891065, Part A: 15 mg BI 891065, Part A: 200 mg BI 891065, Part A: 25 mg BI 891065, Part A: 400 mg BI 981065, Part A: 5 mg BI 891065, Part A: 50 mg BI 891065, Part B: 200 mg BI 891065 QD + 240 mg BI 754091, Part B: 200 mg BI 981065 BID + 240 mg BI 754091, Part B: 50 mg BI 891065 QD + 240 mg BI 754091 |
| BI 754091Part B | Drug | Part B: 200 mg BI 891065 QD + 240 mg BI 754091, Part B: 200 mg BI 981065 BID + 240 mg BI 754091, Part B: 400 mg BI 891065 QD + 240 mg BI 754091, Part B: 50 mg BI 891065 QD + 240 mg BI 754091 |
Primary outcome
Part A - Maximum Tolerated Dose (MTD) of BI 891065
Time frame: First treatment cycle (MTD evaluation period), up to 21 days.
Maximum tolerated dose (MTD) defined as the highest dose with less than 25% risk of the true Dose-limiting toxicity (DLT) rate being above 33% during the MTD evaluation period.
Part A - Number of Patients With Dose-limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period
Time frame: First treatment cycle (MTD evaluation period), up to 21 days.
DLT is defined as: Hematologic toxicities for patients with solid tumors: Any Grade 5 toxicity; Neutropenia ≥Grade 4 lasting for >5 days; Febrile neutropenia of any duration; Neutropenia Grade 3 with documented infection; Grade thrombocytopenia 4, or Grade 3 with bleeding or require platelet transfusion; Grade 4 anemia unexplained by underlying disease. Non-hematological toxicities: AST or ALT >3xULN and concurrent total bilirubin >2xULN without initial findings of cholestasis; ≥Grade 4 AST or ALT; Any ≥Grade 3 non-hematologic toxicity with some exceptions listed in protocol; Any Grade 2 pneumonitis; Any Grade 2 related uveitis, eye pain, or blurred vision that does not respond to topical therapy and does not improve to Grade 1 severity within 2 weeks or requires systemic treatment; Any treatment-related ≥Grade 2 toxicity that persists and results in an inability to administer BI 754091 on Cycle 2 Day 1.
Part B: Maximum Tolerated Dose (MTD) of BI 891065 in Combination With Ezabenlimab
Time frame: First treatment cycle (MTD evaluation period), up to 21 days.
Maximum tolerated dose (MTD) of BI 891065 in combination with ezabenlimab, defined as the highest dose with less than 25% risk of the true Dose-limiting toxicity (DLT) rate being above 33% during the MTD evaluation period.
Part B: Number of Patients With Dose-limiting Toxicities (DLTs) in the Maximum Tolerated Dose (MTD) Evaluation Period
Time frame: First treatment cycle (MTD evaluation period), up to 21 days.
DLT is defined as: Hematologic toxicities for patients with solid tumors: Any Grade 5 toxicity; Neutropenia ≥Grade 4 lasting for >5 days; Febrile neutropenia of any duration; Neutropenia Grade 3 with documented infection; Grade thrombocytopenia 4, or Grade 3 with bleeding or require platelet transfusion; Grade 4 anemia unexplained by underlying disease. Non-hematological toxicities: AST or ALT >3xULN and concurrent total bilirubin >2xULN without initial findings of cholestasis; ≥Grade 4 AST or ALT; Any ≥Grade 3 non-hematologic toxicity with some exceptions listed in protocol; Any Grade 2 pneumonitis; Any Grade 2 related uveitis, eye pain, or blurred vision that does not respond to topical therapy and does not improve to Grade 1 severity within 2 weeks or requires systemic treatment; Any treatment-related ≥Grade 2 toxicity that persists and results in an inability to administer BI 754091 on Cycle 2 Day 1.
12 secondary outcomes
Part A: Number of Patients With Dose-limiting Toxicities (DLT) During the Entire On-treatment Period
Time frame: From first drug administration until last drug administration plus residual effect period of 30 days, up to 282 days.
Part A: Number of Patients With Objective Response (OR)
Time frame: Up to 252 days.
Part A: Maximum Measured Plasma Concentration of BI 891065 at Steady State (Cmax,ss)
Time frame: Just before drug intake and 0.5**, 1, 2, 3, 4*, 5, 6, 7, 8, 10**, 12*, 24, 36, 47.917, 167.917, 263.917, 335.917, 336.5**, 337, 338, 339, 340*, 341, 342, 343, 344, 346**, 348*, 359.917 hours after drug administration on day 1.
Part A: Area Under the Concentration Time Curve of BI 891065 Over a Dosing Interval at Steady State (AUCtau,ss)
Time frame: Just before drug intake and 0.5**, 1, 2, 3, 4*, 5, 6, 7, 8, 10**, 12*, 24, 36, 47.917, 167.917, 263.917, 335.917, 336.5**, 337, 338, 339, 340*, 341, 342, 343, 344, 346**, 348*, 359.917 hours after drug administration on day 1.
Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Time frame: Just before drug intake and 0.5**, 1, 2, 3, 4*, 5, 6, 7, 8, 10**, 12*, 24, 36, 47.917, 167.917, 263.917, 335.917, 336.5**, 337, 338, 339, 340*, 341, 342, 343, 344, 346**, 348*, 359.917 hours after drug administration on day 1.
Part B: Number of Patients With Dose-limiting Toxicities (DLTs) Observed During the Entire Treatment Period
Time frame: From first drug administration until last drug administration plus residual effect period of 30 days, up to 386 days.
Part B: Number of Patients With Objective Response (OR)
Time frame: Up to 356 days.
Part B: Area Under the Concentration-time Curve of BI 891065 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Time frame: At 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 336.5, 337, 338, 339, 341, 342, 343, 344, 346, 359.5, 360.5, 361, 362, 363, 365, 366, 367, 368, 370 and 383.917 hours after intake of BI 891065 at day 1, cycle 1.
Part B: Area Under the Concentration Time Curve of BI 891065 Over a Dosing Interval at Steady State (AUCtau,ss)
Time frame: At 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 336.5, 337, 338, 339, 341, 342, 343, 344, 346, 359.5, 360.5, 361, 362, 363, 365, 366, 367, 368, 370 and 383.917 hours after intake of BI 891065 at day 1, cycle 1.
Part B: Maximum Measured Plasma Concentration of BI 891065 at Steady State (Cmax,ss)
Time frame: At 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 336.5, 337, 338, 339, 341, 342, 343, 344, 346, 359.5, 360.5, 361, 362, 363, 365, 366, 367, 368, 370 and 383.917 hours after intake of BI 891065 at day 1, cycle 1.
Part B: Maximum Measured Plasma Concentration (Cmax) of BI 754091 in the First Treatment Cycle
Time frame: Predose and 1, 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 359.5, 383.917, 504, 998 and 999 hours after intake of BI 754091 at day 1, cycle 1.
Part B: Area Under the Concentration-time Curve of BI 754091 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Time frame: Predose and 1, 1.417, 2, 2.5, 3.5, 4.5, 6.5, 7.5, 8.5, 9.5, 11.5, 25.417, 167.917, 263.917, 335.917, 359.5, 383.917, 504, 998 and 999 hours after intake of BI 754091 at day 1, cycle 1.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41408891Patel MR, Hamilton EP, George B, Kretschmar G, Harada A, Graeser R, Eleftheraki A, Tachibana Y, Yamamoto N. The Second Mitochondria-Derived Activator of Caspases Mimetic BI 891065 in Patients With Advanced Solid Tumors: Results From Two Phase I Studies. Cancer Med. 2025 Dec;14(24):e71451. doi: 10.1002/cam4.71451.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BI 891065 and BI 754091 in people with Neoplasms and Neoplasm Metastasis, run by Boehringer Ingelheim at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A - Maximum Tolerated Dose (MTD) of BI 891065 (time frame: First treatment cycle (MTD evaluation period), up to 21 days.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03166631, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2024.