NeoplasmsPhase 1NCT04147247

A Trial to Find the Safe Dose for BI 905681 in Patients With Incurable Tumours or Tumours That Have Spread

A Phase 1 study testing BI 905681 in people with Neoplasms, run by Boehringer Ingelheim at 3 sites in United States.

Completed

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

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Neoplasms
What is being tested?: BI 905681
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 21 participants
Where: 3 sitesUnited States
Study dates: 23 Dec 2019to 27 May 2021
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

Histologically or cytologically confirmed diagnosis of an advanced, unresectable and/or metastatic non-haematologic malignancy. Patient must have measurable or evaluable lesions (according to Response Evaluation Criteria in Solid Tumours (RECIST) v 1.1).
Patient who has failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options.
Patients willing to undergo mandatory tumour biopsy at the time points specified in the protocol.
Eastern Cooperative Oncology Group (ECOG) Score of 0 or 1 (R01-0787).
Adequate organ function defined as all of the following:
Absolute neutrophil count (ANC) ≥1.5 x 10^9/L; haemoglobin ≥9.0 g/dL; platelets ≥100 x 10^9/L without the use of haematopoietic growth factors within 4 weeks of start of study medication.

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Total bilirubin ≤1.5 x the upper limit of normal (ULN), except for patients with Gilbert's syndrome: total bilirubin ≤3 x ULN or direct bilirubin ≤1.5 x ULN.
Creatinine ≤1.5 x ULN. If creatinine is >1.5 x ULN, patient is eligible if concurrent creatinine clearance ≥50 ml/min (measured or calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula or Japanese version of CKD-EPI formula for Japanese patients).
Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3 x ULN if no demonstrable liver metastases, or otherwise ≤5 x ULN
Alkaline Phosphatase (ALP) <5 x ULN
At least 18 years of age at the time of consent or over the legal age of consent in countries where that is greater than 18 years.
Signed and dated written informed consent in accordance with International Conference on Harmonisation (ICH) - Good Clinical Practice (GCP) and local legislation prior to admission to the trial
Life expectancy ≥3 months at the start of treatment in the opinion of the investigator
Further inclusion criteria apply

Who cannot join

Osteoporosis ≥ CTCAE Grade 2
Osteoporotic compression fracture within 12 months prior to informed consent which is clinically significant in the opinion of the investigator.
Further exclusion criteria apply

Trial locations and contacts

3 sites in 1 country.

United States3 sites

Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Florida Cancer Specialists
Sarasota, Florida, 34232

Other trials in United States

About this study

Official title: An Open-label, Phase I Trial to Determine the Maximum-tolerated Dose and Investigate Safety, Pharmacokinetics and Efficacy of BI 905681 Administered Intravenously in Patients With Advanced Solid Tumours

The primary objective of this trial is to determine the maximum tolerated dose (MTD)/optimal biological dose (OBD) of BI 905681 given as an intravenous infusion and to determine the recommended dose and dosing schedule for further trials in the development of BI 905681. The MTD will be defined based on the frequency of patients experiencing dose-limiting toxicities (DLTs) during the MTD/DLT evaluation period, which is defined as the first cycle of treatment. Separate MTDs will be determined for Schedule A and Schedule B.

The secondary objective of the trial is to determine the pharmacokinetic (PK) profile of BI 905681.

Read the detailed description

Study was opened to recruitment until 29-Oct-2021, however from 15-Apr-2021 no patient was recruited.

Conditions: Neoplasms
Being tested: BI 905681
Medical subject headings: Neoplasms

What participants receive

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

BI 905681Drug
Infusion

Study groups in NCT04147247
Study group	Role	What they receive
1.0 milligram/kilogram BI 905681	Experimental	Subjects received an intravenous infusion of 1.0 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met. Receives: Drug: BI 905681
2.5 milligram/kilogram BI 905681	Experimental	Subjects received an intravenous infusion of 2.5 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met. Receives: Drug: BI 905681
5.0 milligram/kilogram BI 905681	Experimental	Subjects received an intravenous infusion of 5.0 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met. Receives: Drug: BI 905681
7.0 milligram/kilogram BI 905681	Experimental	Subjects received an intravenous infusion of 7.0 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met. Receives: Drug: BI 905681
8.5 milligram/kilogram BI 905681	Experimental	Subjects received an intravenous infusion of 8.5 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met. Receives: Drug: BI 905681

What is being measured

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

The Maximum Tolerated Dose (MTD)/Optimal Biological Dose (OBD) of BI 905681
The MTD/OBD of BI 905681. The MTD will be assessed based on the number of patients experiencing Dose Limiting Toxicities (DLTs), graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, in the first cycle of treatment (3 weeks). The MTD is defined as the highest dose with less than 25% risk of the true DLT rate being equal to or above 33%.
Measured: The first cycle of treatment, up to 21 days.
Number of Patients Experiencing Adverse Events (AEs) During the Entire Treatment Period
Number of patients experiencing adverse events (AEs) during the entire treatment period.
Measured: From the first administration of study till the last administration of study drug +42 days, up to 126 days.

Secondary outcomes (2)

Cmax: Maximum Measured Concentration of BI 905681 in Serum After First Infusion
Cmax: maximum measured concentration of BI 905681 in serum after first infusion.
Measured: 5 minutes before and 1, 1.5, 4, 8, 24, 72, 168, 336 and 504 (5 minutes before 2nd infusion) hours following the first infusion.
AUC0-tz: Area Under the Serum Concentration-time Curve Over the Time Interval From 0 to the Last Measured Time Point (tz)
AUC0-tz: area under the serum concentration-time curve over the time interval from 0 to the last measured time point (tz).
Measured: 5 minutes before and 1, 1.5, 4, 8, 24, 72, 168, 336 and 504 (5 minutes before 2nd infusion) hours following the first infusion.

Timeline

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

23 Dec 201927 May 2021

First posted1 Nov 2019
Study start23 Dec 2019
Primary completion6 May 2021
Study completion27 May 2021

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: Sequential
Masking: None (open label)
Enrolment: 21 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04147247
Sponsor's protocol ID: 1424-0001
Other IDs: 2019-003490-25, 2019
Status last verified: Nov 2023
First submitted: 30 Oct 2019
Last updated: 29 Nov 2023
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
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

Spigel DR, Wang JS, Pronk L, Muskens B, Teufel M, Bashir B, Burris H. A phase I dose escalation study of the LRP5 antagonist BI 905681 in patients with advanced and metastatic solid tumors. ESMO Open. 2024 Nov;9(11):103730. doi: 10.1016/j.esmoop.2024.103730.
PubMed 39617535

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 29 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Phase I Trial to Determine the Maximum-tolerated Dose and Investigate Safety, Pharmacokinetics and Efficacy of BI 905681 Administered Intravenously in Patients With Advanced Solid Tumours
ClinicalTrials.gov ID: NCT04147247
Acronym / sponsor ID: 1424-0001
Conditions: Neoplasms
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 21 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 23 Dec 2019 (actual)
Primary completion: 6 May 2021 (actual)
Study completion: 27 May 2021 (actual)
First posted: 1 Nov 2019 (actual)
Results: Posted 29 Nov 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The secondary objective of the trial is to determine the pharmacokinetic (PK) profile of BI 905681.

Detailed description

Study was opened to recruitment until 29-Oct-2021, however from 15-Apr-2021 no patient was recruited.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
1.0 milligram/kilogram BI 905681	Experimental	Drug: BI 905681Subjects received an intravenous infusion of 1.0 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met.
2.5 milligram/kilogram BI 905681	Experimental	Drug: BI 905681Subjects received an intravenous infusion of 2.5 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met.
5.0 milligram/kilogram BI 905681	Experimental	Drug: BI 905681Subjects received an intravenous infusion of 5.0 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met.
7.0 milligram/kilogram BI 905681	Experimental	Drug: BI 905681Subjects received an intravenous infusion of 7.0 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met.
8.5 milligram/kilogram BI 905681	Experimental	Drug: BI 905681Subjects received an intravenous infusion of 8.5 milligram/kilogram BI 905681 on day 1 of each cycle (1 cycle = 21 days). Patients may continue on treatment for unlimited cycles, until criteria for stopping treatment are met.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

Histologically or cytologically confirmed diagnosis of an advanced, unresectable and/or metastatic non-haematologic malignancy. Patient must have measurable or evaluable lesions (according to Response Evaluation Criteria in Solid Tumours (RECIST) v 1.1).
Patient who has failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options.
Patients willing to undergo mandatory tumour biopsy at the time points specified in the protocol.
Eastern Cooperative Oncology Group (ECOG) Score of 0 or 1 (R01-0787).
Adequate organ function defined as all of the following:

Key exclusion criteria (3 listed)

Osteoporosis ≥ CTCAE Grade 2
Osteoporotic compression fracture within 12 months prior to informed consent which is clinically significant in the opinion of the investigator.
Further exclusion criteria apply

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 905681Infusion	Drug	1.0 milligram/kilogram BI 905681, 2.5 milligram/kilogram BI 905681, 5.0 milligram/kilogram BI 905681, 7.0 milligram/kilogram BI 905681, 8.5 milligram/kilogram BI 905681

Primary outcome

The Maximum Tolerated Dose (MTD)/Optimal Biological Dose (OBD) of BI 905681
Time frame: The first cycle of treatment, up to 21 days.
The MTD/OBD of BI 905681. The MTD will be assessed based on the number of patients experiencing Dose Limiting Toxicities (DLTs), graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, in the first cycle of treatment (3 weeks). The MTD is defined as the highest dose with less than 25% risk of the true DLT rate being equal to or above 33%.
Number of Patients Experiencing Adverse Events (AEs) During the Entire Treatment Period
Time frame: From the first administration of study till the last administration of study drug +42 days, up to 126 days.
Number of patients experiencing adverse events (AEs) during the entire treatment period.

2 secondary outcomes

Cmax: Maximum Measured Concentration of BI 905681 in Serum After First Infusion
Time frame: 5 minutes before and 1, 1.5, 4, 8, 24, 72, 168, 336 and 504 (5 minutes before 2nd infusion) hours following the first infusion.
AUC0-tz: Area Under the Serum Concentration-time Curve Over the Time Interval From 0 to the Last Measured Time Point (tz)
Time frame: 5 minutes before and 1, 1.5, 4, 8, 24, 72, 168, 336 and 504 (5 minutes before 2nd infusion) hours following the first infusion.

Results and safety

Results posted to the registry on 29 Nov 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
1.0 Milligram/Kilogram BI 905681	3	0
2.5 Milligram/Kilogram BI 905681	4	0
5.0 Milligram/Kilogram BI 905681	5	0
7.0 Milligram/Kilogram BI 905681	4	0
8.5 Milligram/Kilogram BI 905681	5	0

Primary outcome: The Maximum Tolerated Dose (MTD)/Optimal Biological Dose (OBD) of BI 905681

Time frame: The first cycle of treatment, up to 21 days.. Number. Unit: milligram/kilogram

Measure	BI 905681 n = 18
Value	NA

Population analysed: MTD Evaluation Set (MTDS): includes all patients who received at least one infusion of BI 905681 and who were not replaced for the MTD determination.

Primary outcome: Number of Patients Experiencing Adverse Events (AEs) During the Entire Treatment Period

Time frame: From the first administration of study till the last administration of study drug +42 days, up to 126 days.. Count of participants. Unit: Participants

Measure	1.0 Milligram/Kilogram BI 905681 n = 3	2.5 Milligram/Kilogram BI 905681 n = 4	5.0 Milligram/Kilogram BI 905681 n = 5	7.0 Milligram/Kilogram BI 905681 n = 4	8.5 Milligram/Kilogram BI 905681 n = 5
Value	2	4	5	4	4

Population analysed: Treated Set (TS): includes all patients who received at least one infusion of BI 905681.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first administration of study till the last administration of study drug +42 to 49 days, up to 133 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
1.0 Milligram/Kilogram BI 905681	1 of 3 (33.3%)	2 of 3 (66.7%)	0 of 3
2.5 Milligram/Kilogram BI 905681	1 of 4 (25%)	4 of 4 (100%)	1 of 4
5.0 Milligram/Kilogram BI 905681	2 of 5 (40%)	5 of 5 (100%)	2 of 5
7.0 Milligram/Kilogram BI 905681	1 of 4 (25%)	4 of 4 (100%)	0 of 4
8.5 Milligram/Kilogram BI 905681	0 of 5 (0%)	4 of 5 (80%)	0 of 5

Limitations and caveats (from the sponsor): Trial was prematurely discontinued due to limited antitumor activity (i.e., lack of a single objective response) \& difficulty in enrolling patients with RNF43 (Ring Finger Protein 43) mutations or R-spondin fusions who were willing to undergo a biopsy. The trial aimed to test two schedules for BI 905681 (A: every three weeks in a 3-week cycle, B: every 2 weeks in a 4-week cycle). Maximum tolerated dose/Recommended Phase 2 dose for Schedule A could not be determined, schedule B was not pursued.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39617535Spigel DR, Wang JS, Pronk L, Muskens B, Teufel M, Bashir B, Burris H. A phase I dose escalation study of the LRP5 antagonist BI 905681 in patients with advanced and metastatic solid tumors. ESMO Open. 2024 Nov;9(11):103730. doi: 10.1016/j.esmoop.2024.103730.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: 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

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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 905681 in people with Neoplasms, 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 14 inclusion and 3 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 29 Nov 2023. 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 29 Nov 2023). 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?

The Maximum Tolerated Dose (MTD)/Optimal Biological Dose (OBD) of BI 905681 (time frame: The first cycle of treatment, up to 21 days.). The study lists 2 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 NCT04147247, 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 29 Nov 2023.