BI 765179 + Ezabenlimab for Advanced Cancer

Recruiting in Palo Alto (17 mi)

+49 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Boehringer Ingelheim

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Other malignancies, Immunodeficiency, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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. These medicines aim to help the immune system fight cancer. Participants are monitored over several years to see if the treatment helps and is safe.

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.

What data supports the effectiveness of the drugs BI 765179 and Ezabenlimab for advanced cancer?

The research shows that similar drugs, like nivolumab and ipilimumab, which are also immune checkpoint inhibitors, have improved survival in patients with advanced non-small cell lung cancer. This suggests that drugs targeting the immune system, like BI 765179 and Ezabenlimab, might also be effective in treating advanced cancers. ^{1 2 3 4 5}

How is the drug combination BI 765179 + Ezabenlimab unique for advanced cancer?

The combination of BI 765179 and Ezabenlimab is unique because it involves two drugs that target the immune system to fight cancer, potentially offering a new approach for advanced cancers where standard treatments may not be effective. This combination may work differently from existing treatments by enhancing the body's immune response against cancer cells. ^{2 3 6 7 8}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• BI 765179 (Monoclonal Antibodies)
• Ezabenlimab (Monoclonal Antibodies)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2023]

2. England 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. [2022]

3. England 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. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

The efficacy and safety of nivolumab, pembrolizumab, and atezolizumab in treatment of advanced non-small cell lung cancer. [2019]

5. England 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. [2022]

6. England 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. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Biomarkers for Clinical Benefit of Immune Checkpoint Inhibitor Treatment-A Review From the Melanoma Perspective and Beyond. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors as first-line and salvage therapy for advanced non-small-cell lung cancer. [2018]