AzTrials
AzTrials

NeoplasmPhase 1NCT04138823

A Study to Test Different Doses of BI 891065 Alone and in Combination With BI 754091 in Asian Patients With Different Types of Advanced Cancer (Solid Tumours)

A Phase 1 study testing BI 891065 in people with Neoplasm, run by Boehringer Ingelheim at 1 site in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The primary objective of this trial is: Part A To determine the Maximum tolerated dose (MTD) and/or the recommended dose (RD) of BI 891065 monotherapy for further development in Asian patients with advanced solid tumours Part B To determine the MTD and/or the RD of BI 891065 in combination with a fixed dose of BI… Read more about this study

Who is it for?
Any age
Conditions the study is for
Neoplasm
What is being tested?
BI 891065
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteJapan
Study dates
26 Nov 2019to 17 May 2023
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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Of legal age (according to local legislation) at screening. No upper limit.
  • Signed and dated written informed consent in accordance with International Council on Harmonisation (ICH) Good Clinical Practice (GCP) and local legislation prior to admission to the trial.
  • 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 per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly, starting with the screening visit and through 6 months after the last dose of study treatment. A list of contraception methods meeting these criteria is provided in the patient information. The requirement of contraception does not apply to women of no childbearing potential and men not able to father a child, but they must have an evidence of such at screening.
  • Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 1
  • 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.
  • Presence of at least one measureable lesion according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1.
Show all 9Show fewer
  • Life expectancy of at least 12 weeks after the start of the treatment according to the Investigator's judgement
  • For Part B: Patients must have at least 1 tumour lesion amenable to biopsy, and must be willing to undergo a biopsy prior to first treatment and after 3 weeks while on therapy.
  • For Part B: Patients with following cancer types: bladder, colon, breast, NSCLC, ovarian, pancreatic, renal, esophagogastric, sarcoma, prostate, and melanoma

Who cannot join

  • Major surgeries (major according to the Investigator's assessment) performed within 12 weeks prior to the first administration or planned within 12 months after screening (e.g., hip replacement), or moderate surgeries (moderate according to the Investigator's assessment) performed within 4 weeks prior to the first administration.
  • Presence of active invasive cancers other than the one treated in this trial within 5 years prior to screening, except for 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 other Second Mitochondrial Activator of Caspases (SMAC) mimetic/IAP inhibitor
  • Patients who have been treated with any other anticancer drug or investigational drug, within 4 weeks or within 5 half-life periods (whichever is shorter) prior to first administration of BI 891065
  • Persistent toxicity from previous treatments that has not resolved to ≤ Grade 1 (except for alopecia and Grade 2 neuropathy due to previous treatments)
Show all 34Show fewer
  • Active, known or suspected autoimmune disease except vitiligo or resolved asthma/atopy
  • (Part B only) Patients removed from previous anti-Programmed-cell-death-protein-1 (PD-1) or anti-Programmed-cell-death ligand-1 (PD-L1) therapy because of a severe immune-related adverse event (irAE)
  • History (including current) of interstitial lung disease or pneumonitis within 5 years
  • Any of the following cardiac criteria:
  • Mean resting corrected QT interval (QTcF) >480 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) of either <50% or less than the lower limit of normal of the institutional standard will be excluded, whichever is lower. 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
  • Inadequate organ function or bone marrow reserve as demonstrated by the following laboratory values:
  • Absolute neutrophil count (ANC) <1.5 x 109/L (<1500/mm^3)
  • Platelet count <100 x 10^9/L (<100,000/mm^3)
  • Haemoglobin <9.0 g/dL
  • Alanine transaminase (ALT) >3 times the upper limit of normal (ULN) if no demonstrable liver lesion(s) (primary or metastases) or >5 times ULN in the presence of liver lesion(s)
  • Aspartate aminotransferase (AST) >3 times the ULN if no demonstrable liver lesion(s) or >5 times ULN in the presence of liver lesion(s)
  • 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
  • Serum creatinine > 1.5 x ULN (measured by enzymatic assay, Isotope dilution mass spectroscopy [IDMS] standardised Jaffe assay, or non-IDMS Jaffe assay). If serum creatinine is > 1.5 x ULN, patient is eligible if concurrent estimated glomerular filtration rate (eGFR) is ≥ 30 mL/min/1.73m^3 (measured or calculated by Chronic Kidney Disease Epidemiology [CKD-EPI] formula)
  • Human immunodeficiency virus (HIV) infection. Test results obtained in routine diagnostics are acceptable if done within 6 months before the informed consent date.
  • Any of the following laboratory evidence of hepatitis virus infection.
  • Positive results of hepatitis B surface (HBs) antigen
  • Presence of hepatitis B core (HBc) antibody together with hepatitis virus B (HBV) Deoxyribonucleic acid (DNA)
  • Presence of hepatitis virus C (HCV) antibody together with HCV Ribonucleic acid (RNA) In Part A, test results obtained in routine clinical practice are acceptable if done within 6 months before the informed consent date.
  • Known relevant hypersensitivity to the trial drugs or their excipients based on the investigator's assessment
  • 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 would make the patient inappropriate for entry into the trial.
  • Chronic alcohol or drug abuse or any condition that, in the Investigator's opinion, makes them an unreliable trial patients, unlikely to complete the trial, or unable to comply with the protocol procedures
  • Women who are pregnant, nursing, or who plan to become pregnant during the trial. Women who are nursing can be enrolled if they stop nursing. In this case, the patient cannot resume nursing even after discontinuation of study treatment.
  • Untreated brain metastasis(es) that may be considered active. Patients with previously treated brain metastases may participate provided they are stable (i.e., without evidence of Progressive disease (PD) by imaging for at least 4 weeks prior to the first dose of trial treatment, and any neurologic symptoms have returned to baseline), and there is no evidence of new or enlarging brain metastases
  • Patients with known leptomeningeal disease
  • Patients receiving systemic treatment with any immunosuppressive medication within 1 week prior to treatment start (steroids of max. 10 mg/day prednisolone equivalent per day are allowed, topical and inhaled steroids are not considered as immunosuppressive).

Trial locations and contacts

1 site in 1 country.

Japan1 site

  • National Cancer Center Hospital

    Tokyo, Chuo-ku, 104-0045

Other trials in Japan

About this study

Official title: An Open Label, Phase I Study of BI 891065 Monotherapy and Combination Therapy of BI 891065 and BI 754091 in Asian Patients With Advanced Solid Tumours

The primary objective of this trial is:

Part A

Read more
  • To determine the Maximum tolerated dose (MTD) and/or the recommended dose (RD) of BI 891065 monotherapy for further development in Asian patients with advanced solid tumours

Part B

  • To determine the MTD and/or the RD of BI 891065 in combination with a fixed dose of BI 754091 at 240 mg for further development in Asian patients with advanced solid tumours

The secondary objectives are:

Part A

  • To document the safety and tolerability, and characterise pharmacokinetics (PK) of BI 891065 as monotherapy in Asian patients with advanced solid tumours

Part B

  • To document the safety and tolerability, and characterise PK of the combination therapy of BI 891065 and BI 754091 in Asian patients with advanced solid tumours
Conditions
Neoplasm
Being tested
BI 891065
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BI 891065Drug

    film-coated tablets

Study groups in NCT04138823
Study groupRoleWhat they receive
Part A: 100 mg BI 891065 QDExperimentalNot described
Receives: Drug: BI 891065
Part A: 200 mg BI 891065 QDExperimentalNot described
Receives: Drug: BI 891065
Part A: 200 mg BI 891065 BIDExperimentalNot described
Receives: Drug: BI 891065

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A: Number of Patients With Dose Limiting Toxicities (DLTs) in the MTD Evaluation Period

    Any of the following adverse events (AEs) were classified as DLTs:

    Haematologic toxicities:

    • Any Grade 5 toxicity.
    • Neutropenia ≥ Grade 4 lasting for >7 days.
    • Febrile neutropenia of any duration (absolute neutrophil count (ANC) <1.0 X 10^9 cells/Liter (L) and fever ≥38.5°Celsius (C)).
    • Neutropenia ≥ Grade 3 with documented infection.
    • Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with bleeding.
    • Thrombocytopenia of any Grade which requires platelet transfusions.
    • Grade 4 anaemia unexplained by underlying disease.
    • Anaemia of any Grade which requires blood transfusions.

    Non-haematological toxicities:

    • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 times upper level of normal (ULN) and concurrent total bilirubin >2 times ULN without initial findings of cholestasis.
    • ≥Grade 4 AST or ALT of any duration.
    • Any ≥Grade 3 non-haematologic toxicity some exceptions as defined in the protocol.

    Measured: First treatment cycle, 21 days from first administration of BI 891065.

  2. Part A: Maximum Tolerated Dose (MTD) of BI 891065

    Maximum tolerated dose (MTD) of BI 891065 in the Part A of the trial is reported.

    MTD was defined as the highest dose with less than 25% risk of the true DLT rate being equal or above 33% during the MTD evaluation period.

    Measured: First treatment cycle, 21 days from first administration of BI 891065.

  3. Part A: Number of Patients With Dose Limiting Toxicities (DLTs) During the Treatment Period

    Any of the following adverse events (AEs) were classified as DLTs:

    Haematologic toxicities:

    • Any Grade 5 toxicity.
    • Neutropenia ≥ Grade 4 lasting for >7 days.
    • Febrile neutropenia of any duration (absolute neutrophil count (ANC) <1.0 X 10^9 cells/Liter (L) and fever ≥38.5°Celsius (C)).
    • Neutropenia ≥ Grade 3 with documented infection.
    • Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with bleeding.
    • Thrombocytopenia of any Grade which requires platelet transfusions.
    • Grade 4 anaemia unexplained by underlying disease.
    • Anaemia of any Grade which requires blood transfusions.

    Non-haematological toxicities:

    • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 times upper level of normal (ULN) and concurrent total bilirubin >2 times ULN without initial findings of cholestasis.
    • ≥Grade 4 AST or ALT of any duration.
    • Any ≥Grade 3 non-haematologic toxicity some exceptions as defined in the protocol.

    Measured: From first administration of BI 891065 until the last administration + 30 days of residual effect period, up to 1164 days.

Secondary outcomes (4)

  1. Maximum Measured Concentration in Plasma of BI 891065 After Administration of the First Dose (Cmax)

    Maximum measured concentration in plasma of BI 891065 after administration of the first dose (Cmax) is reported.

    Measured: Within 5 minutes before and 0.5 hours (h), 1h, 2h, 3h, 5h, 6h, 7h, 8h, 10h, 24h, 36h and 48h after first BI 891065 administration.

  2. Part A: Maximum Measured Concentration in Plasma of BI 891065 at Steady State (Cmax,ss)

    Maximum measured concentration in plasma of BI 891065 at steady state (Cmax,ss) is reported.

    Measured: Within 5 minutes before and 0.5 hours (h), 1h, 2h, 3h, 5h, 6h, 7h, 8h, 10h and 24 h after drug administration of BI 891065 on Day 15 of Cycle 1.

  3. Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma 24 Hours After Administration of the First Dose (AUC0-24)

    Area under the concentration-time curve of BI 891065 in plasma 24 hours after administration of the first dose (AUC0-24) is reported.

    Measured: Within 5 minutes before and 0.5 hours (h), 1h, 2h, 3h, 5h, 6h, 7h, 8h, 10h and 24h after first administration of BI 891065 on Day 1 of Cycle 1.

  4. Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma Over a Uniform Dosing Interval τ at Steady State (AUCτ,ss)

    Area under the concentration-time curve of BI 891065 in plasma over a uniform dosing interval τ at steady state (AUCτ,ss) is reported. τ=24 hours (h) for the once daily dosing arms and τ=12 h for the twice daily dosing arm.

    Measured: Within 5 minutes before and 0.5 hours (h), 1h, 2h, 3h, 5h, 6h, 7h, 8h, 10h and 24 h after drug administration of BI 891065 on Day 15 of Cycle 1.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Oct 2019
  2. Study start26 Nov 2019
  3. Primary completion17 May 2023
  4. Study completion17 May 2023

Resources

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
Sequential
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04138823
Sponsor's protocol ID
1379-0006
Status last verified
Oct 2024
First submitted
21 Oct 2019
Last updated
9 Oct 2024
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BI 891065 in people with Neoplasm, run by Boehringer Ingelheim at 1 site in Japan.

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 9 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: finished, as of the sponsor's last update on 9 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. 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 9 Oct 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: Number of Patients With Dose Limiting Toxicities (DLTs) in the MTD Evaluation Period (time frame: First treatment cycle, 21 days from first administration of BI 891065.). The study lists 3 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 NCT04138823, 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 9 Oct 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in