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

NCT05087992 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 1412-00032021-003041-37
• Study Type: interventional
• Target: 13
• Locations: 5 countries
• Sites: 5

Brief Summary

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.

Conditions

Gastrointestinal Cancer, Metastatic

Outcome Measures

Primary Outcomes (4)

• Determination of the Maximum Tolerated Dose (MTD) of BI 905711

  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.

  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.

• Number of Patients With Dose Limiting Toxicity (DLT) During MTD Evaluation

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

  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.

• Confirmed Objective Response (OR)

  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.

  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.

• Number of PDAC Patients With DLTs During the MTD Evaluation Period Assessed in the First 6 Patients

  In safety run-in part of Pancreatic Ductal Adenocarcinoma (PDAC) cohort. Number of PDAC patients with DLTs during the MTD evaluation period assessed in the first 6 patients is presented.

  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.

Secondary Outcomes (12)

• Maximum Measured Plasma Concentration of BI 905711 During the First Cycle (Cmax)

  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 After Multiple Cycles (Cmax)

  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 During the First Cycle (AUC0-336)

  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 After Multiple Cycles (AUC0-336)

  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.

• Progression Free Survival (PFS)

  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.

Study Arms (3)

0.6 mg/kg BI 905711 + FOLFIRI + bevacizumab

EXPERIMENTAL

Patients with colorectal adenocarcinoma (CRC) received a single administration of 0.6 milligrams (mg) / kilograms (kg) of BI 905711 intravenously on Day 3 of each 14-day cycle. Patients also received FOLFIRI (irinotecan: 180 mg/squaremeters (m2) over 1.5 hours (hrs), leucovorin: 400 mg/m2 (in Japan: levoleucovorin: 200 mg/m2) over 2 hrs, fluorouracil: 400 mg/m2 bolus or 2400 mg/m2 46 hrs continuous infusion) in combination with bevacizumab, 5 mg/kg over 30 minutes (min) intravenously on Day 1 of each 14-day cycle.

Drug: BI 905711; Drug: FOLFIRI; Drug: Bevacizumab

1.2 mg/kg BI 905711 + FOLFIRI + bevacizumab

EXPERIMENTAL

Patients with colorectal adenocarcinoma (CRC) received a single administration of 1.2 mg/kg of BI 905711 intravenously on Day 3 of each 14-day cycle. Patients also received FOLFIRI (irinotecan: 180 mg/m2 over 1.5 hours (hrs), leucovorin: 400 mg/m2 (in Japan: levoleucovorin: 200 mg/m2) over 2 hrs, fluorouracil: 400 mg/m2 bolus or 2400 mg/m2 46 hrs continuous infusion) in combination with bevacizumab, 5 mg/kg over 30 minutes (min) intravenously on Day 1 of each 14-day cycle.

Drug: BI 905711; Drug: FOLFIRI; Drug: Bevacizumab

FOLFIRI + bevacizumab

ACTIVE COMPARATOR

Patients with colorectal adenocarcinoma (CRC) received FOLFIRI (irinotecan: 180 mg/m2 over 1.5 hours (hrs), leucovorin \[or levoleucovorin\]: 400 mg/m2 (in Japan: levoleucovorin: 200 mg/m2) over 2 hrs, fluorouracil: 400 mg/m2 bolus or 2400 mg/m2 46 hrs continuous infusion) in combination with bevacizumab, 5 mg/kg over 30 minutes (min) intravenously on Day 1 of each 14-day cycle.

Drug: FOLFIRI; Drug: Bevacizumab

Interventions

BI 905711 DRUG

BI 905711

0.6 mg/kg BI 905711 + FOLFIRI + bevacizumab; 1.2 mg/kg BI 905711 + FOLFIRI + bevacizumab

FOLFIRI DRUG

FOLFIRI

0.6 mg/kg BI 905711 + FOLFIRI + bevacizumab; 1.2 mg/kg BI 905711 + FOLFIRI + bevacizumab; FOLFIRI + bevacizumab

Bevacizumab DRUG

Bevacizumab

0.6 mg/kg BI 905711 + FOLFIRI + bevacizumab; 1.2 mg/kg BI 905711 + FOLFIRI + bevacizumab; FOLFIRI + bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated written informed consent in accordance with International Council of Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
• Of legal adult age (according to local legislation) at screening.
• Histologically or cytologically confirmed, advanced unresectable or metastatic colorectal adenocarcinoma.
• Colorectal adenocarcinoma (CRC): Patients who have Progressive disease (PD) after prior oxaliplatin-based first line therapy or within 6 months after the end of oxaliplatin-based adjuvant therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Life expectancy ≥ 3 months in the opinion of the investigator.
• Availability and willingness to provide tumor tissue (fresh biopsy or archival) for biomarker analysis. Only non-significant 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, the recruitment of the patient may proceed on a case-by-case basis after agreement between the investigator and BI. In such a case, an archived tumor tissue specimen must be submitted.
• Adequate hepatic, pancreatic, renal and bone marrow functions as defined by all of the below:
• Total bilirubin ≤ 1.5 x institutional upper level of normal (ULN).
• Alanine transaminase (ALT) and Aspartate transaminase (AST) ≤2.5 x institutional ULN or ≤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 (≥ 0.05L/min) (measured or calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula or Japanese version of CKD-EPI formula for Japanese patients).
• Absolute neutrophil count (ANC) ≥ 1.5 x 1\^9/L, ≥ 1.5 x 10\^3/μL, or ≥ 1500/mm\^3
• Platelets ≥ 100 x 10\^9/L, ≥ 100 x 10\^3/μL, or ≥ 100 x 10\^3/mm\^3

You may not qualify if:

• Any prior irinotecan-based therapy in the metastatic setting.
• Previous systemic anti-cancer therapy within the specified timeframe from the last dose intake to the first dose of trial treatment as follows:
• Any non-investigational drug, including anti-angiogenic agents (bevacizumab or ramucirumab or aflibercept) and anti-EGFR antibodies (cetuximab or panitumumab), within 14 days.
• Any investigational drug or other antibodies including immune checkpoint inhibitors, within 28 days.
• Currently enrolled in another investigational device or drug trial. Patients who are in follow-up/observation for another clinical trial are eligible.
• 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.
• 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.
• 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 v5.0 grade ≥ 2.
• Known history of human immunodeficiency virus (HIV) 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 hepatitis B virus deoxyribonucleic acid (HBV-DNA)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (5)

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Beijing Cancer Hospital

Beijing, 100036, China

Location

HOP la Milétrie

Poitiers, 86021, France

Location

National Cancer Center Hospital East

Chiba, Kashiwa, 277-8577, Japan

Location

Related Links

• Related Info

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Neoplasm Metastasis

Interventions

IFL protocol; Bevacizumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Based on available preliminary data from phase I clinical studies (1412.1 and 1412.3), the decision was made to stop BI 905711 (TRAILR2/CDH17) development program. This decision is not related to any safety concerns or unfavorable benefit/risk balance, but to the lack of predictive biomarkers and the limited efficacy particularly in the context of the evolving treatment landscape for advanced colorectal cancer (CRC) and other gastrointestinal (GI) cancers.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1a non randomized, Phase 1b randomized.

Study Record Dates

• First Submitted: October 11, 2021
• First Posted: October 21, 2021
• Study Start: November 24, 2021
• Primary Completion: October 23, 2023
• Study Completion: November 14, 2023
• Last Updated: February 19, 2025
• Results First Posted: February 19, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); FR (1); CN (1); BE (1); JP (1)