BI 905711 + Chemotherapy for Gastrointestinal Cancer

No longer recruiting at 9 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must be taking: Chemotherapy, Bevacizumab

Must not be taking: Anti-angiogenics, Anti-EGFR

Disqualifiers: Irinotecan, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: Up to 54 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new drug, BI 905711, combined with chemotherapy and sometimes another medication, can shrink tumors in people with advanced colorectal or pancreatic cancer. The first part of the study aims to find a safe dose of BI 905711, while the second part assesses its effectiveness in reducing tumor size. The researchers seek participants with advanced colorectal or pancreatic cancer, especially those for whom prior treatments were ineffective. Participants will receive treatment every two weeks and remain in the trial as long as they benefit and tolerate the medication. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had certain cancer treatments recently, like specific drugs or radiation therapy, before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BI 905711 is being tested with chemotherapy and bevacizumab to determine a dose that people can tolerate with minimal side effects. In earlier studies, patients with colorectal cancer received BI 905711 alongside these treatments to assess the safe dosage of the new drug.

Reports suggest that the combination, particularly with FOLFIRI and bevacizumab, is generally well-tolerated, meaning most participants did not experience severe side effects. However, this study remains in the early stages, so researchers continue to learn about the treatment's safety.

Prospective trial participants should consult a healthcare provider to understand what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BI 905711 for gastrointestinal cancer because it offers a new approach by targeting a specific cancer pathway. Unlike most treatments that rely solely on chemotherapy, BI 905711 is an antibody that may enhance the effects of chemotherapy. This makes it a unique candidate for potentially improving outcomes when combined with the standard regimen of FOLFIRI and bevacizumab. By integrating this novel mechanism, there's hope for better efficacy in treating colorectal adenocarcinoma.

What evidence suggests that this trial's treatments could be effective for gastrointestinal cancer?

Research has shown that BI 905711 can effectively kill certain colorectal cancer cells by targeting specific proteins on these cells, leading to their destruction. Earlier studies found that BI 905711 works well with chemotherapy to shrink tumors in lab tests. In this trial, participants will receive different doses of BI 905711 combined with chemotherapy and bevacizumab, or they will receive chemotherapy and bevacizumab alone. Early trials have shown promise for the combination of BI 905711, chemotherapy, and bevacizumab, suggesting it may help reduce tumor size in people with advanced colorectal cancer. While the initial results are encouraging, more research is needed to confirm these findings in larger groups of patients. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

Inclusion Criteria

Of legal adult age (according to local legislation) at screening.

Eastern Cooperative Oncology Group (ECOG) performance status ≤1.

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.

Exclusion Criteria

You have taken any non-experimental drugs, like bevacizumab, ramucirumab, aflibercept, cetuximab, or panitumumab, within the past 14 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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants with colorectal cancer receive BI 905711 combined with chemotherapy and bevacizumab to find the highest dose they can tolerate.

Up to 35 days

Every 2 weeks

Treatment

Participants receive BI 905711, chemotherapy, and bevacizumab every 2 weeks to test if BI 905711 makes tumors shrink.

Up to 54 weeks

Every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• BI 905711
• FOLFIRI

How Is the Trial Designed?

Group I: 1.2 mg/kg BI 905711 + FOLFIRI + bevacizumab Experimental Treatment 3 Interventions

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.

Group II: 0.6 mg/kg BI 905711 + FOLFIRI + bevacizumab Experimental Treatment 3 Interventions

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.

Group III: FOLFIRI + bevacizumab Active Control 2 Interventions

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.

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

In a study of 69 Asian patients with metastatic colorectal cancer, the combination of FOLFOXIRI and bevacizumab resulted in a high progression-free survival (PFS) rate of 75.2% at 10 months, indicating its effectiveness as a first-line treatment.

However, this regimen was associated with significant adverse events, particularly high rates of neutropenia (72.5%) and hypertension (34.8%), highlighting the need for careful monitoring, especially in patients with specific UGT1A1 genetic polymorphisms that increase the risk of severe neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicenter Clinical Phase II Study of FOLFOXIRI Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer: QUATTRO Study. Oki, E., Kato, T., Bando, H., et al.[2022]

The maximum tolerated dose (MTD) of irinotecan for patients with the UGT1A1 *1/*1 genotype is 310 mg/m2, while for those with the *1/*28 genotype, it is 260 mg/m2, indicating that genetic differences can influence drug tolerance in metastatic colorectal cancer treatment.

Bevacizumab does not significantly affect the pharmacokinetics of irinotecan, suggesting that the dosing adjustments based on genotype can be made without concern for altered drug metabolism due to this additional treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genotype-Guided Dosing Study of FOLFIRI plus Bevacizumab in Patients with Metastatic Colorectal Cancer. Toffoli, G., Sharma, MR., Marangon, E., et al.[2022]

In a study of 115 patients with advanced gastric cancer, the combination of irinotecan, 5-fluorouracil (5-FU), and folinic acid (FA) showed a higher overall response rate of 42.4% and a median survival time of 10.7 months compared to 32.1% and 6.9 months for the irinotecan/cisplatin combination.

The irinotecan/5-FU/FA regimen had a better safety profile, with significantly lower rates of severe neutropenia (27% vs. 65.7%) compared to irinotecan/cisplatin, making it the preferred choice for further investigation in a phase III trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study. Pozzo, C., Barone, C., Szanto, J., et al.[2020]

Irinotecan has been shown to significantly prolong survival in patients with 5-FU-resistant colorectal cancer compared to best supportive care or 5-FU-based chemotherapy, based on Phase III studies.

Combining irinotecan with other treatments, such as raltitrexed or oral fluoropyrimidines, has shown promising results in terms of safety and efficacy, with response rates exceeding 30% and median survival benefits in various cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical advances with topoisomerase I inhibitors in gastrointestinal malignancies. Armand, JP., Cunningham, D., van Cutsem, E., et al.[2019]

The modified 5-fluorouracil/leucovorin/irinotecan (mFOLFIRI) regimen showed a response rate of 29.7% and a clinical benefit rate of 57.2% in 91 patients with advanced gastric cancer, indicating its efficacy as a second-line treatment.

Despite its effectiveness, the mFOLFIRI regimen was associated with significant adverse events, including neutropenia in 18.7% of patients, highlighting the need for careful monitoring and potential dose modifications during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified 5-fluorouracil/leucovorin/irinotecan as a feasible and efficacious second-line chemotherapeutic regimen in advanced gastric cancers. Ramaswamy, A., Ostwal, V., Gupta, K., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.115

A phase Ia/b first-in-human, open-label, multicenter study ... In Phase Ia, pts received BI 905711 every 14 days. One pt with colorectal cancer (CRC) was enrolled at each of the 2 lowest dose levels (0.02/ ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05087992

A Study to Find the Best Dose of BI 905711 in Combination ... 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 ...

3. aacrjournals.org aacrjournals.org/mct/article/20/1/96/92979/Selective-Tumor-Cell-Apoptosis-and-Tumor

Selective Tumor Cell Apoptosis and Tumor Regression in ... Here, we show that BI 905711 effectively triggered apoptosis in a broad panel of CDH17-positive colorectal cancer tumor cells in vitro. Efficient induction of ...

4. withpower.com withpower.com/trial/phase-1-gastrointestinal-neoplasms-9-2021-d8572

BI 905711 + Chemotherapy for Gastrointestinal Cancer This trial is for adults with advanced colorectal or pancreatic cancer. It tests a new drug, BI 905711, combined with standard treatments to find the safest ...

5. boehringer-ingelheim.com boehringer-ingelheim.com/us/media/press-releases/boehringer-ingelheim-advances-novel-bi-specific-trailr2-cdh17-antibody-phase-1-clinical-trial

BI Advances Novel Bi-specific TRAILR2/CDH17 Antibody First-in-class bi-specific antibody BI 905711 activates a pathway in TRAILR2 and CDH17 co-expressing tumor cells that leads to their destruction.

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)00903-6/pdf

Novocure Ltd In phase Ia, approximately 20 patients with CRC will receive intravenous BI 905711 at escalating doses (starting dose 0.6 mg/kg) on day 3 of 14- day cycles, ...

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/92/NCT05087992/Prot_000.pdf

Clinical Trial Protocol To evaluate the efficacy and safety of BI 905711 in combination with FOLFIRI plus bevacizumab in the CRC cohort, and define RP2D. • To evaluate ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2949362/

Bevacizumab in combination with folfiri chemotherapy in ... Bevacizumab in combination with folfiri appears to be well tolerated, and efficacy is consistent with trial reports.