Gastrointestinal NeoplasmsPhase 1NCT04137289
A Study to Find a Safe and Effective Dose of BI 905711 in Patients With Advanced Gastrointestinal Cancer
A Phase 1 study testing BI 905711 in people with Gastrointestinal Neoplasms and Cholangiocarcinoma, run by Boehringer Ingelheim at 18 sites in 8 countries.
Trial summary
Phase 1a - Explore safety and establish the maximum tolerated dose (MTD)/recommended dose levels for phase Ib expansion phase of BI 905711 based on the frequency of patients experiencing dose limiting toxicities (DLTs) during the MTD evaluation period. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Neoplasms, Cholangiocarcinoma, Pancreatic Neoplasms
- What is being tested?
- BI 905711
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 18 sitesin 8 countries
- Study dates
- 11 Mar 2020to 27 Nov 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- a. Phase Ia (dose escalation only)
- Histologically or cytologically confirmed, advanced unresectable or metastatic gastrointestinal cancers of following histologies:
- Colorectal adenocarcinoma
- Gastric adenocarcinoma
- Esophageal adenocarcinoma
- Pancreatic adenocarcinoma
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- Cholangiocarcinoma and gallbladder carcinoma
- Small intestine adenocarcinoma b. Phase Ib (expansion phase)
- Histologically or cytologically confirmed, advanced unresectable or metastatic colorectal adenocarcinoma.
- Patient who has failed all available conventional therapies known to confer clinical benefit for their disease based on local approved standards. For patients with colorectal cancer, prior treatment with regorafenib or TAS-102 is optional.
- Phase Ia (dose escalation) only: Patient with either measurable or non-measurable/non-evaluable disease.
- Phase Ia (expanded cohort) and Phase Ib (expansion phase) only: At least one target lesion that can be accurately measured per RECIST v.1.1
- Availability and willingness to provide an archived tumor tissue specimen and undergo tumor biopsy before treatment. Pre-treatment fresh tumor biopsy collections for biomarker analyses are considered optional in phase Ia and mandatory in phase Ib. Only nonsignificant risk procedures per the investigator's judgment will be used to obtain any biopsies specified in this study. In case a fresh tumor biopsy cannot be obtained due to before mentioned reasons an archived tumor tissue specimen obtained within ≤6 months of screening must be submitted. In case the patient undergoes baseline tumor biopsy, an archived tumor tissue specimen must be submitted regardless of the date of collection.
- Adequate hepatic, renal and bone marrow functions as defined by all of the below:
- Total bilirubin ≤ 1.5 x institutional Upper Level of Normal (ULN) (≤ 3 x institutional ULN for patient with Gilbert's syndrome)
- ALT and AST ≤2.5 x institutional ULN (≤5 x institutional ULN for patients with known liver metastases)
- Serum creatinine ≤1.5x institutional ULN. If creatinine is > 1.5 x ULN, patient is eligible if concurrent creatinine clearance ≥ 50 ml/min (>0.05 L/min) (measured or calculated by CKD-EPI formula or Japanese version of CKD-EPI formula for Japanese patients).
- ANC ≥ 1.0x 10^9/L (≥ 1.0 x 10^3/μL, ≥ 1,000/mm3)
- Platelets ≥ 100x10^9/ L (≥ 100 x 10^3/μL, ≥ 100 x 10^3/mm3)
- Hemoglobin (Hb) ≥8.5 g/dl, ≥ 85 g/L, or ≥ 5.3 mmol/L (without transfusion within previous week)
- Serum lipase ≤ 1.5 institutional ULN
- Recovery from any adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 of previous anti-cancer therapies to baseline or CTCAE grade 1, except for alopecia CTCAE grade 2, sensory peripheral neuropathy CTCAE grade ≤ 2 or considered not clinically significant.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- Life expectancy ≥ 3 months in the opinion of the investigator
- Of legal adult age (according to local legislation) at screening
- Signed and dated written informed consent in accordance with ICH-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.
Who cannot join
- Previous systemic anti-cancer therapy within the specified timeframe from the last dose intake to the first dose of trial treatment as shown below:
- Any non-investigational drug, including anti-angiogenic antibodies (bevacizumab or ramucirumab) and anti-EGFR antibodies (cetuximab or panitumumab), within 14 days.
- Any investigational drug or other antibodies including immune checkpoint inhibitors, within 28 days.
- Radiation therapy within 4 weeks prior to start of treatment. However, palliative radiotherapy for symptomatic metastasis is allowed if completed within 2 weeks prior to start of treatment but must be discussed with the sponsor.
- Any 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 neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal (GI) 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. Any history of stroke or myocardial infarction within 6 months prior to screening.
- Known pathological condition of GI tract, liver and pancreas, excluding the disease under study, that may interfere with assessment of drug safety or may increase the risk of toxicity:
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- inflammatory bowel disease
- chronic pancreatitis
- other serious GI pathological conditions by judgment of the investigator e.g. autoimmune disease with GI involvement, unexplained active diarrhea CTCAE grade ≥2 according to CTCAE v5.0.
- Known history of human immunodeficiency virus infection.
- Any of the following laboratory evidence of hepatitis virus infection. Test results obtained in routine diagnostics are acceptable if done within 14 days before the informed consent date:
- Positive results of hepatitis B surface (HBs) antigen
- Presence of HBc antibody together with HBV-DNA
- Presence of hepatitis C RNA
- Active concomitant malignancies, other than the one treated in this trial.
- Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes the patient an unreliable trial participant or unlikely to comply with the protocol requirements or not expected to complete the trial as scheduled.
- Women who are pregnant, nursing, or who plan to become pregnant while in the trial; female patients who do not agree to the interruption of breast feeding from the start of study treatment to within 30 days after the last study treatment.
- Presence of uncontrolled or symptomatic brain or subdural metastases. Inclusion of patients with brain metastases who have completed local therapy and are considered stable by the investigator, or with newly identified asymptomatic brain metastases at screening will be allowed. Use of corticosteroids is allowed if the dose was stable for at least 1 week before the baseline MRI.
- Patients who are under judicial protection and patients who are legally institutionalized
- Major surgery (major according to the investigator's assessment) performed within 3 weeks prior to treatment start or planned within 3 months after screening, e.g. hip replacement.
- Any of the following cardiac criteria:
- Resting corrected QT interval (QTc) >470 msec
- Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting ECGs, e.g., complete left bundle branch block, third degree heart block
- Patients with an ejection fraction (EF) <50% 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, multi-gated acquisition scan). 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.
- Known hypersensitivity to the trial medication and/or its components i.e. polysorbate 20, sodium citrate, lysine hydrochloride, sucrose, citric acid.
Trial locations and contacts
18 sites in 8 countries.
18 sites in 8 countries
United States4 sites
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Yale Cancer Center
New Haven, Connecticut, 06511
Memorial Sloan-Kettering Cancer Center
New York, New York, 10022
START South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, 78229
France4 sites
HOP Jean Minjoz
Besançon, 25030
CTR Leon Berard
Lyon, 69373
HOP la Milétrie
Poitiers, 86021
CTR Eugène Marquis
Rennes, 35042
Spain3 sites
Hospital Vall d'Hebron
Barcelona, 08035
Hospital Ramón y Cajal
Madrid, 28034
Hospital Clínico de Valencia
Valencia, 46010
China2 sites
Beijing Cancer Hospital
Beijing, 100142
The Sixth Affiliated Hospital of Sun Yat-sen University
Guangzhou, 510655
About this study
Official title: A First-in-human Phase Ia/b, Open Label, Multicentre, Dose Escalation Study of BI 905711 in Patients With Advanced Gastrointestinal Cancers
Phase 1a - Explore safety and establish the maximum tolerated dose (MTD)/recommended dose levels for phase Ib expansion phase of BI 905711 based on the frequency of patients experiencing dose limiting toxicities (DLTs) during the MTD evaluation period. The MTD evaluation period is defined as the first two treatment cycles (from first dose administration until the day preceding the third dose administration or end of REP in case of discontinuation before start of Cycle 3).
Phase 1a - Explore pharmacokinetics/pharmacodynamics, and efficacy to guide the determination of a potentially effective dose range for phase Ib in the absence of MTD.
Phase 1b - Evaluate efficacy and safety of BI 905711 at a potentially effective dose range and determine the Recommended Phase 2 Dose (RP2D)
- Being tested
- BI 905711
- Medical subject headings
- Gastrointestinal Neoplasms, Cholangiocarcinoma, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BI 905711Drug
BI 905711
| Study group | Role | What they receive |
|---|---|---|
| BI 905711 0.02 mg/kg, Q2W | Experimental | Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 0.02 milligram/kilogram (mg/kg) of BI 905711 intravenously as a powder for solution for infusion, on Day 1 of each 14-day cycle treatment, once every two weeks. Receives: Drug: BI 905711 |
| BI 905711 0.06 mg/kg, Q2W | Experimental | Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 0.06 mg/kg of BI 905711 intravenously as a powder for solution for infusion, on Day 1 of each 14-day cycle treatment, once every two weeks. Receives: Drug: BI 905711 |
| BI 905711 0.2 mg/kg, Q2W | Experimental | Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 0.2 mg/kg of BI 905711 intravenously on Day 1 of each 14-day cycle treatment, once every two weeks. Receives: Drug: BI 905711 |
| BI 905711 0.6 mg/kg, Q2W | Experimental | Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 0.6 mg/kg of BI 905711 intravenously on Day 1 of each 14-day cycle treatment, once every two weeks. Participants in both the dose escalation and dose expansion phases at this dose were pooled together for baseline analysis. Receives: Drug: BI 905711 |
| BI 905711 0.6 mg/kg, QW | Experimental | Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 0.6 mg/kg of BI 905711 intravenously on Day 1 of each 14-day cycle treatment, once every week for 3 weeks and then 1 week off (3 weeks on, 1 week off). Receives: Drug: BI 905711 |
| BI 905711 1.2 mg/kg, Q2W | Experimental | Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 1.2 mg/kg of BI 905711 intravenously on Day 1 of each 14-day cycle treatment, once every two weeks. Participants in both the dose escalation and dose expansion phases at this dose were pooled together for baseline analysis. Receives: Drug: BI 905711 |
| BI 905711 2.4 mg/kg, Q2W | Experimental | Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 2.4 mg/kg of BI 905711 intravenously on Day 1 of each 14-day cycle treatment, once every two weeks. Participants in both the dose escalation and dose expansion phases at this dose were pooled together for baseline analysis. Receives: Drug: BI 905711 |
| BI 905711 3.6 mg/kg, Q2W | Experimental | Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 3.6 mg/kg of BI 905711 intravenously on Day 1 of each 14-day cycle treatment, once every two weeks. Receives: Drug: BI 905711 |
| BI 905711 4.8 mg/kg, Q2W | Experimental | Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 4.8 mg/kg of BI 905711 intravenously on Day 1 of each 14-day cycle treatment, once every two weeks. Receives: Drug: BI 905711 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of BI 905711 in Phase 1a
Maximum tolerated dose (MTD) was defined as the highest dose with less than 25% risk of the true drug limiting dose (DLT) rate being equal to or above 33% during the MTD evaluation period. The MTD was to be considered reached if one of the following criteria was fulfilled: the posterior probability of the true DLT rate in the target interval (0.16, 0.33) of the MTD is above 0.5 or at least 15 patients have been treated in phase 1a, of which at least 6 were at the MTD.
Measured: From cycle 1 Day 1 until the second administration of study treatment (two 14-day treatment cycles).
Number of Patients With Dose-limiting Toxicity (DLT) During the MTD Evaluation Period in Phase 1a
Number of patients with dose-limiting toxicity (DLT) during the MTD evaluation period is reported.
Measured: From cycle 1 Day 1 until the day before cycle 3 Day 1 (two 14-day treatment cycles).
Confirmed Objective Response (OR) for Phase 1a and Phase 1b Combined
Confirmed objective response (OR) as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in patients with measurable disease is reported. This was defined as the best overall response of complete response (CR) or partial response (PR), where best overall response was the best response recorded from the start of the study treatment until the earliest of disease progression, death, or last evaluable tumor assessment and before start of subsequent anticancer therapy.
Measured: From the first administration of trial medication until the earliest of progressive disease (PD), death or last evaluable tumor assessment before start of subsequent anti-cancer therapy, up to 48 weeks.
Progression-free Survival (PFS)
This was evaluated per RECIST 1.1 criteria for target lesions and assessed by CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. Overall response at each time point was evaluated by target lesion, non-target lesions and new lesions together, according to RECIST 1.1. Objective response (OR) was defined as best overall response of confirmed CR or confirmed PR according to RECIST 1.1.
Measured: From the first administration of trial medication until tumor progression or death, whichever occurred first, up to 48 weeks.
Secondary outcomes (12)
Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1a
Maximum measured plasma concentration (Cmax) of BI 905711 during the first cycle in phase 1a is reported.
Measured: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion in cycle 1.
Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1a
Maximum measured plasma concentration (Cmax) of BI 905711 during the third cycle in phase 1a is reported.
Measured: Cycle 3: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion.
Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the First Cycle in Phase 1a
Area under the concentration-time curve (AUC0-336) of BI 905711 during the first cycle in phase 1a is reported.
Measured: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion in cycle 1 .
Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the Third Cycle in Phase 1a
Area under the concentration-time curve (AUC0-336) of BI 905711 during the third cycle in phase 1a is reported.
Measured: Cycle 3: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion.
Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1b
Maximum measured plasma concentration (Cmax) of BI 905711 during the first cycle in phase 1b is reported.
Measured: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after infusion in cycle 1. For 0.6 mg/kg QW only, there was no 336 hrs timepoint as the next drug was already given after 168 hrs.
Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1b
Maximum measured plasma concentration (Cmax) of BI 905711 during the third cycle in phase 1b is reported.
Measured: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after infusion in cycle 1. For 0.6 mg/kg QW only, there was no 336 hrs timepoint as the next drug was already given after 168 hrs.
Area Under the Concentration-time Curve (AUC0-336) in Plasma of BI 905711 During the First Cycle in Phase 1b
Area under the concentration-time curve (AUC0-336) in plasma of BI 905711 during the first cycle in phase 1b is reported. 11. The AUC calculation includes an extrapolation from 168 hrs to 336 hrs to account for the weekly dosing schedule.
Measured: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after infusion in cycle 1. For 0.6 mg/kg QW only, there was no 336 hrs timepoint as the next drug was already given after 168 hrs.
Area Under the Concentration-time Curve (AUC0-336) in Plasma of BI 905711 During the Third Cycle in Phase 1b
Area under the concentration-time curve (AUC0-336) in plasma of BI 905711 during the third cycle in phase 1b is reported. The AUC calculation includes an extrapolation from 168 hrs to 336 hrs to account for the weekly dosing schedule.
Measured: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after infusion in cycle 1. For 0.6 mg/kg QW only, there was no 336 hrs timepoint as the next drug was already given after 168 hrs.
Number of Patients With Treatment-emergent Adverse Events (AEs)
The number of patients with treatment-emergent adverse events (AEs) is reported, namely, all adverse events occurring between start of treatment and end of the residual effect period (REP). Adverse events that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'.
Measured: From start of treatment until the last dose of trial medication plus the residual effect period (REP), up to 358 days.
Maximum Percentage Change From Baseline in the Sum of Target Lesion Diameters
Radiological (CT scan) tumor shrinkage, defined as the difference between the minimum post-baseline sum of longest diameters of target lesions and the baseline sum of the longest diameters of the same set of target lesions according to RECIST 1.1 is reported. Negative values indicate a reduction in the sum of target lesion diameters and positive values indicate an increase.
Measured: At baseline and every 8 weeks (± 7 days) until progression or start of further treatment for disease, up to 48 weeks.
Duration of Overall Response
The duration of overall response was measured from the time measurement criteria were first met for complete response (CR) / partial response (PR) (whichever was first recorded) until the first date that recurrent or progression disease (PD) was objectively documented (taking as reference for PD the smallest measurements recorded in the study) according to RECIST 1.1.
Measured: From the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or PD is objectively documented, up to 48 weeks.
Disease Control
Disease control was defined as complete response (PR), partial response (PR), or stable disease according to RECIST 1.1 from the start of treatment until the earliest of progression disease (PD), death or last evaluable tumor assessment and before start of subsequent anti-cancer therapy. This endpoint analyzed the number of patients meeting this criterion.
Measured: From the start of treatment until the earliest of PD, death or last evaluable tumor assessment and before start of subsequent anti-cancer therapy, up to 48 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2019
- Study start11 Mar 2020
- Primary completion26 Jul 2023
- Study completion27 Nov 2023
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 Gastrointestinal 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase 1a: Dose escalation (non randomised) Phase 1b: Dose expansion (randomised)
- Masking
- None (open label)
- Enrolment
- 110 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
- NCT04137289
- Sponsor's protocol ID
- 1412-0001
- Other IDs
- 2018-003268-29, 2018
- Status last verified
- Mar 2025
- First submitted
- 22 Oct 2019
- Last updated
- 25 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets.
Publications
Garcia-Martinez JM, Wang S, Weishaeupl C, Wernitznig A, Chetta P, Pinto C, Ho J, Dutcher D, Gorman PN, Kroe-Barrett R, Rinnenthal J, Giragossian C, Impagnatiello MA, Tirapu I, Hilberg F, Kraut N, Pearson M, Kuenkele KP. Selective Tumor Cell Apoptosis and Tumor Regression in CDH17-Positive Colorectal Cancer Models using BI 905711, a Novel Liver-Sparing TRAILR2 Agonist. Mol Cancer Ther. 2021 Jan;20(1):96-108. doi: 10.1158/1535-7163.MCT-20-0253. Epub 2020 Oct 9.
PubMed 33037135
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A First-in-human Phase Ia/b, Open Label, Multicentre, Dose Escalation Study of BI 905711 in Patients With Advanced Gastrointestinal Cancers
- ClinicalTrials.gov ID
- NCT04137289
- Acronym / sponsor ID
- 1412-0001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 11 Mar 2020 (actual)
- Primary completion
- 26 Jul 2023 (actual)
- Study completion
- 27 Nov 2023 (actual)
- First posted
- 24 Oct 2019 (actual)
- Results
- Posted 25 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 1a - Explore safety and establish the maximum tolerated dose (MTD)/recommended dose levels for phase Ib expansion phase of BI 905711 based on the frequency of patients experiencing dose limiting toxicities (DLTs) during the MTD evaluation period. The MTD evaluation period is defined as the first two treatment cycles (from first dose administration until the day preceding the third dose administration or end of REP in case of discontinuation before start of Cycle 3).
Phase 1a - Explore pharmacokinetics/pharmacodynamics, and efficacy to guide the determination of a potentially effective dose range for phase Ib in the absence of MTD.
Phase 1b - Evaluate efficacy and safety of BI 905711 at a potentially effective dose range and determine the Recommended Phase 2 Dose (RP2D)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 9
- Model description
- Phase 1a: Dose escalation (non randomised) Phase 1b: Dose expansion (randomised)
| Arm | Type | Receives |
|---|---|---|
| BI 905711 0.02 mg/kg, Q2W | Experimental | Drug: BI 905711Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 0.02 milligram/kilogram (mg/kg) of BI 905711 intravenously as a powder for solution for infusion, on Day 1 of each 14-day cycle treatment, once every two weeks. |
| BI 905711 0.06 mg/kg, Q2W | Experimental | Drug: BI 905711Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 0.06 mg/kg of BI 905711 intravenously as a powder for solution for infusion, on Day 1 of each 14-day cycle treatment, once every two weeks. |
| BI 905711 0.2 mg/kg, Q2W | Experimental | Drug: BI 905711Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 0.2 mg/kg of BI 905711 intravenously on Day 1 of each 14-day cycle treatment, once every two weeks. |
| BI 905711 0.6 mg/kg, Q2W | Experimental | Drug: BI 905711Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 0.6 mg/kg of BI 905711 intravenously on Day 1 of each 14-day cycle treatment, once every two weeks. Participants in both the dose escalation and dose expansion phases at this dose were pooled together for baseline analysis. |
| BI 905711 0.6 mg/kg, QW | Experimental | Drug: BI 905711Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 0.6 mg/kg of BI 905711 intravenously on Day 1 of each 14-day cycle treatment, once every week for 3 weeks and then 1 week off (3 weeks on, 1 week off). |
| BI 905711 1.2 mg/kg, Q2W | Experimental | Drug: BI 905711Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 1.2 mg/kg of BI 905711 intravenously on Day 1 of each 14-day cycle treatment, once every two weeks. Participants in both the dose escalation and dose expansion phases at this dose were pooled together for baseline analysis. |
| BI 905711 2.4 mg/kg, Q2W | Experimental | Drug: BI 905711Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 2.4 mg/kg of BI 905711 intravenously on Day 1 of each 14-day cycle treatment, once every two weeks. Participants in both the dose escalation and dose expansion phases at this dose were pooled together for baseline analysis. |
| BI 905711 3.6 mg/kg, Q2W | Experimental | Drug: BI 905711Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 3.6 mg/kg of BI 905711 intravenously on Day 1 of each 14-day cycle treatment, once every two weeks. |
| BI 905711 4.8 mg/kg, Q2W | Experimental | Drug: BI 905711Patients with confirmed, advanced unresectable or metastatic GI cancers received a single administration (Cycle 1) and multiple administrations (Cycle 3) of 4.8 mg/kg of BI 905711 intravenously on Day 1 of each 14-day cycle treatment, once every two weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- a. Phase Ia (dose escalation only)
- Histologically or cytologically confirmed, advanced unresectable or metastatic gastrointestinal cancers of following histologies:
- Colorectal adenocarcinoma
- Gastric adenocarcinoma
- Esophageal adenocarcinoma
Key exclusion criteria (25 listed)
- Previous systemic anti-cancer therapy within the specified timeframe from the last dose intake to the first dose of trial treatment as shown below:
- Radiation therapy within 4 weeks prior to start of treatment. However, palliative radiotherapy for symptomatic metastasis is allowed if completed within 2 weeks prior to start of treatment but must be discussed with the sponsor.
- Any 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 neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal (GI) 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. Any history of stroke or myocardial infarction within 6 months prior to screening.
- Known pathological condition of GI tract, liver and pancreas, excluding the disease under study, that may interfere with assessment of drug safety or may increase the risk of toxicity:
- Known history of human immunodeficiency virus infection.
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 905711BI 905711 | Drug | BI 905711 0.02 mg/kg, Q2W, BI 905711 0.06 mg/kg, Q2W, BI 905711 0.2 mg/kg, Q2W, BI 905711 0.6 mg/kg, Q2W, BI 905711 0.6 mg/kg, QW, BI 905711 1.2 mg/kg, Q2W, BI 905711 2.4 mg/kg, Q2W, BI 905711 3.6 mg/kg, Q2W, BI 905711 4.8 mg/kg, Q2W |
Primary outcome
Maximum Tolerated Dose (MTD) of BI 905711 in Phase 1a
Time frame: From cycle 1 Day 1 until the second administration of study treatment (two 14-day treatment cycles).
Maximum tolerated dose (MTD) was defined as the highest dose with less than 25% risk of the true drug limiting dose (DLT) rate being equal to or above 33% during the MTD evaluation period. The MTD was to be considered reached if one of the following criteria was fulfilled: the posterior probability of the true DLT rate in the target interval (0.16, 0.33) of the MTD is above 0.5 or at least 15 patients have been treated in phase 1a, of which at least 6 were at the MTD.
Number of Patients With Dose-limiting Toxicity (DLT) During the MTD Evaluation Period in Phase 1a
Time frame: From cycle 1 Day 1 until the day before cycle 3 Day 1 (two 14-day treatment cycles).
Number of patients with dose-limiting toxicity (DLT) during the MTD evaluation period is reported.
Confirmed Objective Response (OR) for Phase 1a and Phase 1b Combined
Time frame: From the first administration of trial medication until the earliest of progressive disease (PD), death or last evaluable tumor assessment before start of subsequent anti-cancer therapy, up to 48 weeks.
Confirmed objective response (OR) as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in patients with measurable disease is reported. This was defined as the best overall response of complete response (CR) or partial response (PR), where best overall response was the best response recorded from the start of the study treatment until the earliest of disease progression, death, or last evaluable tumor assessment and before start of subsequent anticancer therapy.
Progression-free Survival (PFS)
Time frame: From the first administration of trial medication until tumor progression or death, whichever occurred first, up to 48 weeks.
This was evaluated per RECIST 1.1 criteria for target lesions and assessed by CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. Overall response at each time point was evaluated by target lesion, non-target lesions and new lesions together, according to RECIST 1.1. Objective response (OR) was defined as best overall response of confirmed CR or confirmed PR according to RECIST 1.1.
12 secondary outcomes
Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1a
Time frame: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion in cycle 1.
Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1a
Time frame: Cycle 3: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion.
Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the First Cycle in Phase 1a
Time frame: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion in cycle 1 .
Area Under the Concentration-time Curve (AUC0-336) of BI 905711 During the Third Cycle in Phase 1a
Time frame: Cycle 3: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after BI 905711 infusion.
Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the First Cycle in Phase 1b
Time frame: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after infusion in cycle 1. For 0.6 mg/kg QW only, there was no 336 hrs timepoint as the next drug was already given after 168 hrs.
Maximum Measured Plasma Concentration (Cmax) of BI 905711 During the Third Cycle in Phase 1b
Time frame: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after infusion in cycle 1. For 0.6 mg/kg QW only, there was no 336 hrs timepoint as the next drug was already given after 168 hrs.
Area Under the Concentration-time Curve (AUC0-336) in Plasma of BI 905711 During the First Cycle in Phase 1b
Time frame: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after infusion in cycle 1. For 0.6 mg/kg QW only, there was no 336 hrs timepoint as the next drug was already given after 168 hrs.
Area Under the Concentration-time Curve (AUC0-336) in Plasma of BI 905711 During the Third Cycle in Phase 1b
Time frame: Within 5 minutes (min) before start of BI 905711 infusion and at 30 min, 7 hours (hrs), 24 hrs, 48 hrs, 168 hrs and 336 hrs after infusion in cycle 1. For 0.6 mg/kg QW only, there was no 336 hrs timepoint as the next drug was already given after 168 hrs.
Number of Patients With Treatment-emergent Adverse Events (AEs)
Time frame: From start of treatment until the last dose of trial medication plus the residual effect period (REP), up to 358 days.
Maximum Percentage Change From Baseline in the Sum of Target Lesion Diameters
Time frame: At baseline and every 8 weeks (± 7 days) until progression or start of further treatment for disease, up to 48 weeks.
Duration of Overall Response
Time frame: From the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that recurrent or PD is objectively documented, up to 48 weeks.
Disease Control
Time frame: From the start of treatment until the earliest of PD, death or last evaluable tumor assessment and before start of subsequent anti-cancer therapy, up to 48 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33037135Garcia-Martinez JM, Wang S, Weishaeupl C, Wernitznig A, Chetta P, Pinto C, Ho J, Dutcher D, Gorman PN, Kroe-Barrett R, Rinnenthal J, Giragossian C, Impagnatiello MA, Tirapu I, Hilberg F, Kraut N, Pearson M, Kuenkele KP. Selective Tumor Cell Apoptosis and Tumor Regression in CDH17-Positive Colorectal Cancer Models using BI 905711, a Novel Liver-Sparing TRAILR2 Agonist. Mol Cancer Ther. 2021 Jan;20(1):96-108. doi: 10.1158/1535-7163.MCT-20-0253. Epub 2020 Oct 9.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets.
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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.
18 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BI 905711 in people with Gastrointestinal Neoplasms and Cholangiocarcinoma, run by Boehringer Ingelheim at 18 sites in 8 countries.
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 27 inclusion and 25 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 25 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, France, Spain, Belgium, China and 3 more countries. 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 25 Mar 2025). 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?
Maximum Tolerated Dose (MTD) of BI 905711 in Phase 1a (time frame: From cycle 1 Day 1 until the second administration of study treatment (two 14-day treatment cycles).). 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 NCT04137289, 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 25 Mar 2025.