A Study To Find A Safe And Effective Dose Of BI 905711 In Patients With Advanced Gastrointestinal Cancer

Study Overview

A Study to Find a Safe and Effective Dose of BI 905711 in Patients With Advanced Gastrointestinal Cancer

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)

N/A

Gastrointestinal Neoplasms
Cholangiocarcinoma
Pancreatic Neoplasms

DRUG: BI 905711

1412-0001
2018-003268-29 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2019-10-22	Results First Submitted 2024-11-25	Last Update Submitted that met QC Criteria 2025-03-24
First Submitted that Met QC Criteria 2019-10-22	Results First Submitted that Met QC Criteria 2025-03-24	Last Update Posted (ACTUAL) 2025-03-25
First Posted (ACTUAL) 2019-10-24	Results First Posted 2025-03-25	Last Verified 2025-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: BI 905711 0.02 mg/kg, Q2W 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,	DRUG: BI 905711 BI 905711
EXPERIMENTAL: BI 905711 0.06 mg/kg, Q2W 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-d	DRUG: BI 905711 BI 905711
EXPERIMENTAL: BI 905711 0.2 mg/kg, Q2W 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	DRUG: BI 905711 BI 905711
EXPERIMENTAL: BI 905711 0.6 mg/kg, Q2W 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	DRUG: BI 905711 BI 905711
EXPERIMENTAL: BI 905711 0.6 mg/kg, QW 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	DRUG: BI 905711 BI 905711
EXPERIMENTAL: BI 905711 1.2 mg/kg, Q2W 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	DRUG: BI 905711 BI 905711
EXPERIMENTAL: BI 905711 2.4 mg/kg, Q2W 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	DRUG: BI 905711 BI 905711
EXPERIMENTAL: BI 905711 3.6 mg/kg, Q2W 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	DRUG: BI 905711 BI 905711
EXPERIMENTAL: BI 905711 4.8 mg/kg, Q2W 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	DRUG: BI 905711 BI 905711

Primary Outcome Measures	Measure Description	Time Frame
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.	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.	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.	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.	From the first administration of trial medication until tumor progression or death, whichever occurred first, up to 48 weeks.

Secondary Outcome Measures	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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'.	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.	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.	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.	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.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Colorectal adenocarcinoma
Gastric adenocarcinoma
Esophageal adenocarcinoma
Pancreatic adenocarcinoma
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.

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:

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General 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.

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