Trial Outcomes & Findings for 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) (NCT NCT04138823)

Last Updated: 2024-10-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

12 participants

Primary outcome timeframe

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

Results posted on

2024-10-09

Participant Flow

This trial was designed as a Phase I, open-label, non-randomised, uncontrolled, multicentre trial to determine the maximum tolerated dose (MTD) or recommended dose of BI 891065, administered as single agent in Part A and in combination with 240 mg of BI 754091 (ezabenlimab) in Part B. After completion of Part A of the trial, Part B of the trial was cancelled as a whole.

All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Participant milestones

Participant milestones
Measure	Part A: 100 mg BI 891065 QD Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 100 milligrams (mg) of BI 891065, composed of two 50 mg film-coated tablets, with 240 milliliters (mL) of water.	Part A: 200 mg BI 891065 QD Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.	Part A: 200 mg BI 891065 BID Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered twice daily (BID) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.
Overall Study STARTED	3	3	6
Overall Study COMPLETED	0	1	0
Overall Study NOT COMPLETED	3	2	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: 100 mg BI 891065 QD Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 100 milligrams (mg) of BI 891065, composed of two 50 mg film-coated tablets, with 240 milliliters (mL) of water.	Part A: 200 mg BI 891065 QD Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.	Part A: 200 mg BI 891065 BID Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered twice daily (BID) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.
Overall Study Clinical disease progression	0	0	1
Overall Study Objective disease progression	3	2	5

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: 100 mg BI 891065 QD n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 100 milligrams (mg) of BI 891065, composed of two 50 mg film-coated tablets, with 240 milliliters (mL) of water.	Part A: 200 mg BI 891065 QD n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.	Part A: 200 mg BI 891065 BID n=6 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered twice daily (BID) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.	Total n=12 Participants Total of all reporting groups
Age, Continuous	53.0 years STANDARD_DEVIATION 12.1 • n=5 Participants	45.7 years STANDARD_DEVIATION 7.5 • n=7 Participants	54.8 years STANDARD_DEVIATION 10.2 • n=5 Participants	52.1 years STANDARD_DEVIATION 10.0 • n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	8 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	12 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	12 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

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

Population: The MTD evaluation set included all patients who were documented to have received at least one dose of trial medication and were considered evaluable for MTD evaluation.

Outcome measures

Outcome measures
Measure	Part A: 100 mg BI 891065 QD n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 100 milligrams (mg) of BI 891065, composed of two 50 mg film-coated tablets, with 240 milliliters (mL) of water.	Part A: 200 mg BI 891065 QD n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.	Part A: 200 mg BI 891065 BID n=6 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered twice daily (BID) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.
Part A: Number of Patients With Dose Limiting Toxicities (DLTs) in the MTD Evaluation Period	1 Participants	0 Participants	2 Participants

PRIMARY outcome

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

Population: The MTD evaluation set included all patients who were documented to have received at least one dose of trial medication and were considered evaluable for MTD evaluation.

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.

Outcome measures

Outcome measures
Measure	Part A: 100 mg BI 891065 QD n=12 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 100 milligrams (mg) of BI 891065, composed of two 50 mg film-coated tablets, with 240 milliliters (mL) of water.	Part A: 200 mg BI 891065 QD Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.	Part A: 200 mg BI 891065 BID Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered twice daily (BID) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.
Part A: Maximum Tolerated Dose (MTD) of BI 891065	NA milligram MTD was not reached during the Part A of the trial because the MTD criteria were not fulfilled for the investigated doses of 100 mg BI 891065 QD, 200 mg BI 891065 QD, and 200 mg BI 891065 BID.	—	—

PRIMARY outcome

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

Population: The treated set (TS) consisted of all patients who received at least one administration of trial medication.

Outcome measures

Outcome measures
Measure	Part A: 100 mg BI 891065 QD n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 100 milligrams (mg) of BI 891065, composed of two 50 mg film-coated tablets, with 240 milliliters (mL) of water.	Part A: 200 mg BI 891065 QD n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.	Part A: 200 mg BI 891065 BID n=6 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered twice daily (BID) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.
Part A: Number of Patients With Dose Limiting Toxicities (DLTs) During the Treatment Period	1 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: 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.

Population: The pharmacokinetic parameter set (PKS) consisted of all patients in the TS who had at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of pharmacokinetic (PK) or due to PK non-evaluability.

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

Outcome measures

Outcome measures
Measure	Part A: 100 mg BI 891065 QD n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 100 milligrams (mg) of BI 891065, composed of two 50 mg film-coated tablets, with 240 milliliters (mL) of water.	Part A: 200 mg BI 891065 QD n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.	Part A: 200 mg BI 891065 BID n=6 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered twice daily (BID) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.
Maximum Measured Concentration in Plasma of BI 891065 After Administration of the First Dose (Cmax)	445 nanomole/Liter Geometric Coefficient of Variation 8.10	761 nanomole/Liter Geometric Coefficient of Variation 48.3	1270 nanomole/Liter Geometric Coefficient of Variation 45.6

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Part A: 100 mg BI 891065 QD n=2 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 100 milligrams (mg) of BI 891065, composed of two 50 mg film-coated tablets, with 240 milliliters (mL) of water.	Part A: 200 mg BI 891065 QD n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.	Part A: 200 mg BI 891065 BID n=4 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered twice daily (BID) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.
Part A: Maximum Measured Concentration in Plasma of BI 891065 at Steady State (Cmax,ss)	996 nanomole/Liter (nmol/L) Geometric Coefficient of Variation 16.7	1370 nanomole/Liter (nmol/L) Geometric Coefficient of Variation 15.8	4630 nanomole/Liter (nmol/L) Geometric Coefficient of Variation 65.6

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Part A: 100 mg BI 891065 QD n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 100 milligrams (mg) of BI 891065, composed of two 50 mg film-coated tablets, with 240 milliliters (mL) of water.	Part A: 200 mg BI 891065 QD n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.	Part A: 200 mg BI 891065 BID n=6 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered twice daily (BID) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.
Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma 24 Hours After Administration of the First Dose (AUC0-24)	5090 hoursnanmole/Liter (hnmol/L) Geometric Coefficient of Variation 1.29	9410 hoursnanmole/Liter (hnmol/L) Geometric Coefficient of Variation 52.1	15500 hoursnanmole/Liter (hnmol/L) Geometric Coefficient of Variation 34.6

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A: 100 mg BI 891065 QD n=2 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 100 milligrams (mg) of BI 891065, composed of two 50 mg film-coated tablets, with 240 milliliters (mL) of water.	Part A: 200 mg BI 891065 QD n=3 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.	Part A: 200 mg BI 891065 BID n=4 Participants Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered twice daily (BID) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.
Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma Over a Uniform Dosing Interval τ at Steady State (AUCτ,ss)	11500 hours nanomole/Liter (hnmol/L) Geometric Coefficient of Variation 8.21	20500 hours nanomole/Liter (hnmol/L) Geometric Coefficient of Variation 15.1	47200 hours nanomole/Liter (hnmol/L) Geometric Coefficient of Variation 64.8

Adverse Events

Part A: 100 mg BI 891065 QD

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part A: 200 mg BI 891065 QD

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part A: 200 mg BI 891065 BID

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part A: 100 mg BI 891065 QD n=3 participants at risk Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 100 milligrams (mg) of BI 891065, composed of two 50 mg film-coated tablets, with 240 milliliters (mL) of water.	Part A: 200 mg BI 891065 QD n=3 participants at risk Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.	Part A: 200 mg BI 891065 BID n=6 participants at risk Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered twice daily (BID) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water.
Gastrointestinal disorders Ileus	0.00% 0/3 • From first administration of BI 891065 until the last administration + 30 days of residual effect period, up to 1164 days. The treated set (TS) consisted of all patients who received at least one administration of trial medication.	0.00% 0/3 • From first administration of BI 891065 until the last administration + 30 days of residual effect period, up to 1164 days. The treated set (TS) consisted of all patients who received at least one administration of trial medication.	16.7% 1/6 • From first administration of BI 891065 until the last administration + 30 days of residual effect period, up to 1164 days. The treated set (TS) consisted of all patients who received at least one administration of trial medication.
Infections and infestations Pharyngitis	0.00% 0/3 • From first administration of BI 891065 until the last administration + 30 days of residual effect period, up to 1164 days. The treated set (TS) consisted of all patients who received at least one administration of trial medication.	0.00% 0/3 • From first administration of BI 891065 until the last administration + 30 days of residual effect period, up to 1164 days. The treated set (TS) consisted of all patients who received at least one administration of trial medication.	16.7% 1/6 • From first administration of BI 891065 until the last administration + 30 days of residual effect period, up to 1164 days. The treated set (TS) consisted of all patients who received at least one administration of trial medication.

Other adverse events

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER