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)

NCT04138823 | Completed Phase 1 Results

• 1 other identifier: 1379-0006
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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 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

Outcome Measures

Primary Outcomes (3)

• 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.

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

• 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.

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

• 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.

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

Secondary Outcomes (4)

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

  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.

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

  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.

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

  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.

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

  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.

Study Arms (3)

Part A: 100 mg BI 891065 QD

EXPERIMENTAL

Drug: BI 891065

Part A: 200 mg BI 891065 QD

EXPERIMENTAL

Drug: BI 891065

Part A: 200 mg BI 891065 BID

EXPERIMENTAL

Drug: BI 891065

Interventions

BI 891065 DRUG

film-coated tablets

Part A: 100 mg BI 891065 QD; Part A: 200 mg BI 891065 BID; Part A: 200 mg BI 891065 QD

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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)
• 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:

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

National Cancer Center Hospital

Tokyo, Chuo-ku, 104-0045, Japan

Location

Related Publications (1)

• 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.

  PMID: 41408891 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Neoplasms

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2019
• First Posted: October 25, 2019
• Study Start: November 26, 2019
• Primary Completion: May 17, 2023
• Study Completion: May 17, 2023
• Last Updated: October 9, 2024
• Results First Posted: October 9, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)