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NCT05087992

A Study to Find the Best Dose of BI 905711 in Combination With Chemotherapy and to Test Whether This Dose Helps People With Advanced Gastrointestinal Cancers

Completed Phase 1 Results posted Last updated 19 February 2025
What this trial tests

Phase 1 trial testing BI 905711 in Gastrointestinal Cancer, Metastatic in 13 participants. Completed in 14 November 2023.

Timeline
24 November 2021
Primary endpoint
23 October 2023
14 November 2023

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment13
Start date24 November 2021
Primary completion23 October 2023
Estimated completion14 November 2023
Sites5 locations across France, Japan, Belgium, China, United States

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

18 and older, any sex, with Gastrointestinal Cancer, Metastatic. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Determination of the Maximum Tolerated Dose (MTD) of BI 905711 Primary · From cycle 1 Day 1 until the day before cycle 3 Day 1 (2 14-day treatment cycles), or end of the residual effect period (REP) (30 days + 5 days) in case of discontinuation before start of cycle 3, up to 35 days.

Maximum tolerated dose (MTD) was defined as the highest dose with less than 25% risk of the true dose-limiting toxicity (DLT) rate being equal 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 was above 0.5, or at least 12 patients had been treated in Phase Ia, of which at least 6 at the MTD.

GroupValue95% CI
BI 905711 + FOLFIRI + BevacizumabNA
Number of Patients With Dose Limiting Toxicity (DLT) During MTD Evaluation Primary · From cycle 1 Day 1 until the day before cycle 3 Day 1 (2 14-day treatment cycles), or end of the REP (30 days + 5 days) in case of discontinuation before start of cycle 3, up to 35 days.

Number of patients with dose limiting toxicity (DLT) during MTD evaluation is presented.

GroupValue95% CI
0.6 mg/kg BI 905711 + FOLFIRI + Bevacizumab0
1.2 mg/kg BI 905711 + FOLFIRI + Bevacizumab2
Confirmed Objective Response (OR) Primary · 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 54 weeks.

Confirmed objective response (OR) as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for target lesions and assessed by MRI in patients with measurable disease, defined as the best overall response of complete response (CR) or partial response (PR), 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.

GroupValue95% CI
0.6 mg/kg BI 905711 + FOLFIRI + Bevacizumab0
1.2 mg/kg BI 905711 + FOLFIRI + Bevacizumab0
FOLFIRI + Bevacizumab0
Maximum Measured Plasma Concentration of BI 905711 During the First Cycle (Cmax) Secondary · At 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 of BI 905711 during the first cycle (Cmax) in phase Ia is presented.

GroupValue95% CI
0.6 mg/kg BI 905711 + FOLFIRI + Bevacizumab6100± 36.6
1.2 mg/kg BI 905711 + FOLFIRI + Bevacizumab11500± 23.9
Maximum Measured Plasma Concentration of BI 905711 After Multiple Cycles (Cmax) Secondary · Cycle 3: At 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 of BI 905711 after multiple cycles (Cmax) in phase Ia is presented.

GroupValue95% CI
0.6 mg/kg BI 905711 + FOLFIRI + Bevacizumab6660± 25.4
1.2 mg/kg BI 905711 + FOLFIRI + Bevacizumab9280± 23.8
Area Under the Concentration-time Curve in Plasma of BI 905711 During the First Cycle (AUC0-336) Secondary · At 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 in plasma of BI 905711 during the first cycle (AUC0-336) in phase Ia is presented.

GroupValue95% CI
0.6 mg/kg BI 905711 + FOLFIRI + Bevacizumab372000± 53.4
1.2 mg/kg BI 905711 + FOLFIRI + Bevacizumab702000± 49.4
Area Under the Concentration Time-curve in Plasma of BI 905711 After Multiple Cycles (AUC0-336) Secondary · Cycle 3: At 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 in plasma of BI 905711 after multiple cycles (AUC0-336) in phase Ia is presented.

GroupValue95% CI
0.6 mg/kg BI 905711 + FOLFIRI + Bevacizumab352000± 73.3
1.2 mg/kg BI 905711 + FOLFIRI + Bevacizumab565000± 29.0
Progression Free Survival (PFS) Secondary · From date of start of treatment to the date of disease progression or death, whichever is earlier as assessed by the investigator according to RECIST 1.1., up to 54 weeks.

Progression-Free Survival (PFS) defined from date of start of treatment to the date of disease progression or death, whichever is earlier as assessed by the investigator according to RECIST 1.1 is presented.

GroupValue95% CI
0.6 mg/kg BI 905711 + FOLFIRI + Bevacizumab31.008.43 – 39.29
1.2 mg/kg BI 905711 + FOLFIRI + Bevacizumab29.5711.71 – 33.43
FOLFIRI + BevacizumabNANA – NA
Maximum Percentage Change From Baseline in the Sum of Longest Target Lesion Diameters Secondary · At baseline and every 8 weeks (± 7 days) until progression or start of further treatment for disease, up to 54 weeks.

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 longest diameters of the same set of target lesions according to RECIST 1.1. is presented. Negative values indicate a reduction in the sum of target lesion diameters and positive values indicate an increase. Median change from baseline was calculated for each patient and then summarized over all patients.

GroupValue95% CI
0.6 mg/kg BI 905711 + FOLFIRI + Bevacizumab-13.9-28.3 – 18.6
1.2 mg/kg BI 905711 + FOLFIRI + Bevacizumab4.5-21.7 – 6.3
Disease Control Secondary · 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 54 weeks.

Disease control, defined as complete response (CR), partial response (PR), or stable disease (SD) lasting at least 16 weeks according to RECIST 1.1 from the start of treatment until the earliest of PD, death or last evaluable tumor assessment and before start of subsequent anti-cancer therapy.

GroupValue95% CI
0.6 mg/kg BI 905711 + FOLFIRI + Bevacizumab248.0120 – 325
1.2 mg/kg BI 905711 + FOLFIRI + Bevacizumab220.5207 – 234

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 54 weeks.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

0.6 mg/kg BI 905711 + FOLFIRI + Bevacizumab
Serious: 4/9 (44%)
Deaths: 3/9
1.2 mg/kg BI 905711 + FOLFIRI + Bevacizumab
Serious: 2/3 (67%)
Deaths: 2/3
FOLFIRI + Bevacizumab
Serious: 0/1 (0%)
Deaths: 0/1

Serious adverse events (14 terms)

ReactionSystem0.6 mg/kg BI 905711 + FOLF…1.2 mg/kg BI 905711 + FOLF…FOLFIRI + Bevacizumab
LeukopeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Abdominal pain upperGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
EnterocolitisGastrointestinal disorders
OesophagitisGastrointestinal disorders
PyrexiaGeneral disorders
Biliary obstructionHepatobiliary disorders
Drug-induced liver injuryHepatobiliary disorders
COVID-19Infections and infestations
Gastroenteritis Escherichia coliInfections and infestations
InfectionInfections and infestations
Oesophageal infectionInfections and infestations
Other adverse events (88 terms — click to expand)

ReactionSystem0.6 mg/kg BI 905711 + FOLF…1.2 mg/kg BI 905711 + FOLF…FOLFIRI + Bevacizumab
Decreased appetiteMetabolism and nutrition disorders
DiarrhoeaGastrointestinal disorders
Neutrophil count decreasedInvestigations
White blood cell count decreasedInvestigations
NauseaGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
AnaemiaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
HypokalaemiaMetabolism and nutrition disorders
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
ConstipationGastrointestinal disorders
StomatitisGastrointestinal disorders
FatigueGeneral disorders
PainGeneral disorders
Blood potassium decreasedInvestigations
Platelet count decreasedInvestigations
Protein total decreasedInvestigations
HeadacheNervous system disorders
ProteinuriaRenal and urinary disorders
CoagulopathyBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
ThrombocytosisBlood and lymphatic system disorders
Ear painEar and labyrinth disorders
VertigoEar and labyrinth disorders
Abdominal distensionGastrointestinal disorders
AscitesGastrointestinal disorders
DyspepsiaGastrointestinal disorders
DysphagiaGastrointestinal disorders
Mouth ulcerationGastrointestinal disorders
AstheniaGeneral disorders
Catheter site inflammationGeneral disorders
Device related thrombosisGeneral disorders
Influenza like illnessGeneral disorders
Non-cardiac chest painGeneral disorders
Oedema peripheralGeneral disorders
Liver disorderHepatobiliary disorders

Most-reported serious reactions: Leukopenia, Neutropenia, Thrombocytopenia, Abdominal pain upper, Diarrhoea, Enterocolitis, Oesophagitis, Pyrexia.

Data from ClinicalTrials.gov NCT05087992 adverse events section.

Sponsor's own description

This study is open to adults with advanced colorectal cancer or with advanced pancreatic cancer. The study has 2 parts. In the first part, participants with colorectal cancer get a medicine called BI 905711 combined with chemotherapy and bevacizumab. The purpose of the first part is to find the highest BI 905711 dose participants can tolerate. In the second part, participants with colorectal cancer or pancreatic cancer get BI 905711 combined with chemotherapy. Some participants also get bevacizumab. The second part tests whether BI 905711 makes tumours shrink. Participants get BI 905711, chemotherapy and bevacizumab about every 2 weeks as an infusion into a vein. Participants can stay in the study as long as they benefit from treatment and can tolerate it. The doctors regularly check the health of the participants and note any health problems that could have been caused by the study treatment. The doctors also monitor the size of the tumour.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The Role of TRAIL in Apoptosis and Immunosurveillance in Cancer.
    Pimentel JM, Zhou JY, Wu GS. · · 2023 · cited 73× · PMID 37345089 · DOI 10.3390/cancers15102752
  2. BI 905711, a TRAILR2/CDH17 Bispecific Antibody, Alone or with Chemotherapy for Patients with Advanced Gastrointestinal Cancers: Phase I Study Findings.
    Harding JJ, Hofheinz R, Élez E, Kuboki Y, et al · · 2026 · PMID 41987415 · DOI 10.1158/2767-9764.crc-25-0638
  3. Cadherin 17 and digestive cancers: from diagnostic to therapeutic opportunities.
    Fernandez B, Lopez L, Matis T, Dabernat S, et al · · 2026 · PMID 41928253 · DOI 10.1186/s13046-026-03693-8
  4. Novel tetravalent bispecific antibody, PSMA/TRAIL‑R2 REGULGENT™, induces selective tumor cell apoptosis without hepatotoxicity.
    Nakayama M, Takagi-Maeda S, Machino Y, Nihira K, et al · · 2025 · PMID 40970352 · DOI 10.3892/or.2025.8988

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