BI 765179 + Ezabenlimab for Advanced Cancer

Recruiting at 68 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Other malignancies, Immunodeficiency, others

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

Compensation: Varies

Number of Visits: 6

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new medicine, BI 765179, either alone or with other medicines for people with advanced cancer. Part 1 seeks to determine the best dose of BI 765179 for individuals with solid tumors, either by itself or with ezabenlimab, an immunotherapy drug. Part 2 examines whether combining BI 765179 with pembrolizumab benefits those with advanced head and neck cancer. Suitable candidates have advanced cancer that has not responded to standard treatments or is unsuitable for them, particularly in cases like head and neck, lung, or stomach cancer. Participants will receive the treatments as infusions, and doctors will monitor their health throughout the trial. 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 treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on immunosuppressive medication, you must stop it 14 days before the first dose of the trial drug, except for certain types of corticosteroids.

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

In a previous study, researchers tested BI 765179 alone and with another drug, ezabenlimab, to assess tolerability in people with advanced cancer. This treatment is a new type of antibody designed to help the immune system fight cancer. Early results suggested that BI 765179 did not present major safety issues in these trials. However, the study remains in an early phase, so researchers continue to collect more safety data.

For the combination of BI 765179 and ezabenlimab, researchers aim to determine the highest dose that people can tolerate safely. They are still identifying the safest way to use these drugs together. It is important to note that this is the first time BI 765179 is being administered to people, so caution is essential.

Overall, while early trials show some promise, the information remains limited. Participants are closely monitored to detect any health problems related to the treatment. Those considering joining this trial should remember that researchers are actively working to ensure the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BI 765179 and Ezabenlimab for advanced cancer because these treatments offer new approaches compared to current standards like chemotherapy and conventional immunotherapies. BI 765179 is particularly unique because it targets a novel pathway involved in cancer cell survival, potentially offering more effective tumor suppression. Ezabenlimab is an innovative checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. Together, these treatments aim to boost the body's immune response against cancer in ways that existing therapies might not, offering hope for better outcomes in advanced cancer cases.

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

Research has shown that BI 765179 is a special type of antibody that activates T-cells, which are crucial for the immune system to fight cancer. In this trial, some participants will receive BI 765179 alone, while others will receive it with pembrolizumab, a drug that helps the immune system identify and attack cancer cells. This combination might be more effective, especially for head and neck cancer. Early results from patients treated with BI 765179 indicate it can activate T-cells in the body, potentially controlling cancer more effectively. Unpublished laboratory studies support further research into this treatment, particularly for advanced cancers that are difficult to treat with current options. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors that didn't respond to standard treatments or for whom such treatments aren't suitable can join. This includes those with certain types of cancers like lung, gastric, and breast cancer, among others. Participants must be over 18, have at least one measurable tumor outside the brain, be in good physical condition (ECOG 0 or 1), and have proper organ function. Women who can bear children and men who can father a child must use effective birth control.

Inclusion Criteria

My cancer is advanced and hasn't responded to standard treatments, or standard treatments aren't suitable for me.

I have signed and understand the consent form for this trial.

I have a tumor outside the brain that can be measured.

Exclusion Criteria

My side effects from past treatments are mild, except for hair loss, nerve pain, tiredness, or hormone issues treated with medication.

I haven't taken strong immune-weakening medicines in the last 2 weeks, except for low-dose steroids or local treatments.

I am on blood thinners that can't be stopped for medical procedures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive BI 765179 alone or in combination with ezabenlimab as infusion into a vein every 3 weeks to determine the maximum tolerated dose.

Up to 3 years

Infusions every 3 weeks

Treatment Part 2

Participants receive BI 765179 in combination with pembrolizumab to assess the objective response in advanced head and neck cancer.

Up to 2 years

Infusions every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• BI 765179
• Ezabenlimab

Trial Overview The trial is testing the highest tolerable dose of BI 765179 alone or combined with ezabenlimab in patients with advanced cancer. Both drugs are antibodies designed to help the immune system fight cancer; this is the first time BI 765179 is being used on people. Treatments are given via infusion every three weeks for up to three years if beneficial and tolerable.

How Is the Trial Designed?

Group I: Phase 1b Cohort 2: pembrolizumab + high dose of BI 765179 Experimental Treatment 2 Interventions

Group II: Phase 1b Cohort 1: pembrolizumab + low dose of BI 765179 Experimental Treatment 2 Interventions

Group III: Phase 1a Arm B: BI 765179 + ezabenlimab Experimental Treatment 2 Interventions

Group IV: Phase 1 Arm A: BI 765179 Experimental Treatment 1 Intervention

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 719 patients with metastatic non-small cell lung cancer, first-line treatment with nivolumab plus ipilimumab and chemotherapy significantly reduced the risk of definitive deterioration in disease-related symptoms and health-related quality of life compared to chemotherapy alone.

While both treatment groups showed no deterioration in symptom burden over time, the combination therapy demonstrated a trend towards improved quality of life, although these changes did not reach the threshold for minimally important differences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in metastatic non-small cell lung cancer: CheckMate 9LA 2-year patient-reported outcomes. Reck, M., Ciuleanu, TE., Cobo, M., et al.[2023]

In the BRIM-3 trial, vemurafenib significantly improved overall survival (13.6 months) and progression-free survival (6.9 months) compared to dacarbazine in patients with advanced BRAF(V600) mutation-positive melanoma, demonstrating its efficacy as a treatment option.

The study included 675 patients and showed that vemurafenib was effective for both BRAF(V600E) and BRAF(V600K) mutations, with median overall survival of 14.5 months for BRAF(V600K) patients, indicating its potential for a broader range of BRAF mutation types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. McArthur, GA., Chapman, PB., Robert, C., et al.[2022]

Single-agent immune checkpoint inhibitors (ICIs) significantly improve overall survival in patients with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥50% compared to platinum-based chemotherapy, with a hazard ratio of 0.68 based on data from 2111 participants across six trials.

Double-agent ICI treatment also likely enhances overall survival in the same patient group, with a hazard ratio of 0.72 from 612 participants in two trials, although data on progression-free survival and quality of life are limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer. Ferrara, R., Imbimbo, M., Malouf, R., et al.[2022]

Platinum-based chemotherapy remains the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) without identifiable genetic mutations, but immune checkpoint inhibitors like pembrolizumab and nivolumab are changing the treatment landscape by significantly improving survival rates with manageable safety profiles.

Pembrolizumab is specifically approved for PD-L1-positive NSCLC, while nivolumab and atezolizumab can be used regardless of PD-L1 expression, highlighting the need for ongoing research into additional biomarkers to better identify patients who will benefit from these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of nivolumab, pembrolizumab, and atezolizumab in treatment of advanced non-small cell lung cancer. Chen, R., Tao, Y., Xu, X., et al.[2019]

Single-agent immune checkpoint inhibitors (ICIs) significantly improve overall survival in patients with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥50% compared to platinum-based chemotherapy, with a hazard ratio of 0.68 based on data from 2111 participants across six trials.

Double-agent ICIs also likely enhance overall survival in the same patient group, showing a hazard ratio of 0.72 from two trials involving 612 participants, although their effects on progression-free survival and quality of life remain unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer. Ferrara, R., Imbimbo, M., Malouf, R., et al.[2022]

Immune checkpoint inhibitors (ICIs) like anti-PD-1 and anti-CTLA-4 antibodies are effective treatments for metastatic melanoma and other advanced cancers, with biomarkers such as PD-L1 expression and tumor mutational load helping to predict patient response.

Current clinical practice uses biomarkers like pre-treatment tumor burden and serum lactate dehydrogenase levels to estimate the effectiveness of ICIs, while emerging research on the gut microbiome and imaging biomarkers may further enhance prediction of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers for Clinical Benefit of Immune Checkpoint Inhibitor Treatment-A Review From the Melanoma Perspective and Beyond. Buder-Bakhaya, K., Hassel, JC.[2022]

Nivolumab is the first immune checkpoint inhibitor approved for treating recurrent non-small-cell lung cancer (NSCLC), showing promise for patients who have not responded to first-line therapies.

Pembrolizumab has also been approved for use in PD-L1-positive recurrent NSCLC, highlighting the growing role of immunotherapy in improving treatment options and outcomes for advanced NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors as first-line and salvage therapy for advanced non-small-cell lung cancer. Decatris, MP., O'Byrne, KJ.[2018]

In a phase 3 trial involving 444 patients with EGFR-mutated non-small-cell lung cancer, the combination of sintilimab, IBI305, and chemotherapy significantly improved progression-free survival compared to chemotherapy alone, with a median of 6.9 months versus 4.3 months (p<0.0001).

The treatment was generally well tolerated, although some serious adverse events were reported, including decreased neutrophil and white blood cell counts, and a few treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial. Lu, S., Wu, L., Jian, H., et al.[2022]

Citations

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positive head and neck squamous cell carcinoma (HNSCC). BI 765179 is a bispecific antibody that simultaneously binds to FAP and CD137 expressed on T-cells, leading to local activation of tumor-specific CD137- ...

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An open-label, Phase Ib dose-expansion study to assess ... An open-label, Phase Ib dose-expansion study to assess the efficacy of CD137 FAP agonist BI 765179 plus pembrolizumab as a first-line treatment ...

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Clinical trial of BI 765179 and ezabenlimab in patients with ... The purpose of this study is to determine the appropriate dose of BI 765179 when administered alone and when administered in combination with ezabenlimab in ...

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BI 765179 + Ezabenlimab for Advanced Cancer This trial is testing a new medicine called BI 765179, alone or with ezabenlimab, for adults with advanced cancer who didn't respond to other treatments.

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BI-765179 - Drug Targets, Indications, Patents The antibody drug is a fully human IgG2 subtype antibody and entered clinical trials in 2011. Although it did not demonstrate the safety issues ...