BI 770371 + Ezabenlimab for Advanced Solid Tumors

Not currently recruiting at 7 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Disqualifiers: Active cancers, Untreated brain metastases, Pneumonitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two experimental antibody treatments, BI 770371 and ezabenlimab, to evaluate their effectiveness in helping the immune system combat advanced solid tumors in patients for whom other treatments have failed. The goal is to determine the highest dose of BI 770371 that patients can safely tolerate, whether administered alone or with ezabenlimab. Participants will receive these treatments every three weeks for up to two years, provided they benefit and can tolerate the treatment. This trial may suit adults with difficult-to-treat advanced cancer who have not succeeded with other therapies and have no remaining standard treatment options. As a Phase 1 trial, the 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 protocol does not specify if you must stop taking your current medications, but it mentions that patients who need to continue taking restricted medications or drugs that might interfere with the trial cannot participate. It's best to discuss your specific medications with the trial team.

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

Research has shown that BI 770371 is generally safe when used alone. So far, studies have not identified a maximum safe dose, indicating it can be taken in high amounts without serious issues. No severe side effects occurred at the highest doses tested.

When combined with ezabenlimab, the results are similar. Early findings suggest this combination is also safe. Both treatments are antibodies that help the immune system fight cancer, and they have not caused major side effects in early tests.

This study is in the early stages (Phase 1). At this point, researchers are determining the safe dosage for people. While the safety data appears promising, further studies will provide a better understanding. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BI 770371 and ezabenlimab for advanced solid tumors because these treatments offer a fresh approach compared to traditional options. Most standard treatments for solid tumors involve chemotherapy, which targets rapidly dividing cells, often leading to significant side effects. However, BI 770371 and ezabenlimab work differently, focusing on enhancing the immune system's ability to fight cancer. Ezabenlimab, an immune checkpoint inhibitor, helps unmask cancer cells, allowing the immune system to attack them more effectively. This novel mechanism of action holds promise for improved outcomes with potentially fewer side effects.

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

Research has shown that BI 770371, which participants in this trial may receive as a monotherapy, may help fight advanced cancers. Early results suggest that BI 770371 is generally safe for patients. Another group in this trial will receive a combination of BI 770371 and ezabenlimab, a drug that helps the immune system attack cancer cells. When combined, early signs indicate effectiveness against tumors. Although BI 770371 is being tested in people for the first time, early study results are hopeful about its effectiveness. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

Adults with advanced solid tumors who have not had success with previous treatments or have no other treatment options can join this study. They must be over 18, able to consent, and have a life expectancy of at least 3 months. Participants should not have active brain metastases or severe allergies to trial drugs.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

I have tried all known treatments for my condition without success.

My side effects from previous cancer treatments are mild or gone, except for hair loss, nerve issues, thyroid problems, or menstrual changes.

Exclusion Criteria

I need to keep taking certain medications that may affect the trial's safety.

I've had severe allergic reactions to other antibody treatments.

I haven't had any active cancer other than basal-cell skin cancer, cervical in situ carcinoma, or local tumors treated over 5 years ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BI 770371 alone or in combination with ezabenlimab as an infusion every 3 weeks

Up to 2 years

Regular visits to the study site

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BI 770371
• ezabenlimab

Trial Overview The trial is testing the highest tolerable dose of BI 770371 alone or combined with ezabenlimab in adults with advanced cancer. Both are antibodies that may boost the immune system's ability to fight cancer. Treatments are given as infusions every three weeks for up to two years if beneficial.

How Is the Trial Designed?

Group I: Monotherapy dose escalation Experimental Treatment 1 Intervention

Group II: Combination therapy dose escalation Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

Ipilimumab has shown a positive impact on overall survival in patients with stage IV melanoma, with long-term follow-up indicating its effectiveness compared to conventional treatments.

While 84.8% of patients experience drug-related adverse events, most are mild to moderate; however, severe reactions can occur, necessitating careful monitoring and management, especially when combined with other therapies like vemurafenib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations. Camacho, LH.[2022]

Cadonilimab, an anti PD-1 and CTLA-4 bispecific antibody, showed limited efficacy in treating previously treated metastatic non-small-cell lung cancer (NSCLC), achieving an objective response rate of only 10% in patients who were immunotherapy naïve after platinum-based chemotherapy.

The treatment was well-tolerated, with only 11.3% of patients experiencing grade 3-4 adverse events, suggesting that cadonilimab could be a viable option for second-line therapy in NSCLC, particularly for those who have not previously received immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, open-label phase Ib/II study of cadonilimab (anti PD-1 and CTLA-4 bispecific antibody) monotherapy in previously treated advanced non-small-cell lung cancer (AK104-202 study). Zhao, Y., Ma, Y., Fan, Y., et al.[2023]

Combination therapy with dabrafenib and trametinib for BRAF-mutated metastatic melanoma showed a high overall response rate, with 64.6% of patients achieving a partial response and 6.2% achieving a complete response, indicating its efficacy in treating this condition.

The treatment was found to be relatively safe, with only 8.3% of patients experiencing severe adverse events, and 62.5% of patients remained on treatment, suggesting good tolerability in a real-life clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined therapy with dabrafenib and trametinib in BRAF-mutated metastatic melanoma in a real-life setting: the INT Milan experience. Cavalieri, S., Di Guardo, L., Cimminiello, C., et al.[2017]

Blocking the PD-1 pathway with specific drugs has shown clinical effectiveness in treating advanced cancers like melanoma and lung cancer, by enhancing the body's anti-tumor immune response.

These PD-1/PD-L1 blocking drugs have a manageable safety profile, making them suitable for outpatient treatment and potential use in combination therapies, with ongoing research focused on identifying biomarkers for better patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antagonists of PD-1 and PD-L1 in Cancer Treatment. Lipson, EJ., Forde, PM., Hammers, HJ., et al.[2022]

The combination of nintedanib (150 mg bid) and pembrolizumab was found to be safe, with a maximum tolerated dose established and only a few patients experiencing significant side effects, such as grade 3 liver enzyme increases.

In this study of 13 patients, 25% achieved a partial response to treatment, and 42% had a durable clinical benefit, indicating that early immune and angiogenic markers may help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, recommended dose, efficacy and immune correlates for nintedanib in combination with pembrolizumab in patients with advanced cancers. Baldini, C., Danlos, FX., Varga, A., et al.[2022]

The combination of lenvatinib, a multikinase inhibitor, and pembrolizumab, a PD-1 inhibitor, shows promising antitumor activity and durable responses in various solid tumors, as indicated by preliminary results from the LEAP clinical trial program.

This combination therapy has a manageable safety profile, suggesting it could be a valuable new treatment option for solid cancers that currently have limited therapeutic alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Taylor, MH., Schmidt, EV., Dutcus, C., et al.[2021]

Cadonilimab, a bispecific PD-1/CTLA-4 antibody, demonstrated a manageable safety profile with 28% of patients experiencing grade 3-4 treatment-related adverse events, indicating it can be safely administered to patients with advanced solid tumors.

In a phase 2 trial, cadonilimab showed promising antitumor activity, with an objective response rate of 32.3% in cervical cancer patients, suggesting its potential effectiveness in treating advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial. Gao, X., Xu, N., Li, Z., et al.[2023]

In a four-year study of 80 patients with non-small cell lung cancer treated with anti-PD-1 and anti-PD-L1 therapies, significant overall survival rates were observed, particularly with nivolumab and pembrolizumab, showing 79.7% survival at 6 months and 100% at first-line treatment for pembrolizumab.

Adverse events were common, occurring in over 84% of patients, with fatigue and respiratory issues being the most reported, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of anti PD-1/PD-L1 antibodies as monotherapy in patients with non-small-cell lung cancer. Zayas-Soriano, M., Bonete-Sánchez, M., Campillo-López, J., et al.[2021]

In a study involving 21 Japanese patients with advanced solid tumors, the maximum tolerated dose (MTD) of BI 836880 was not reached, indicating a favorable safety profile for this treatment.

BI 836880, both as a monotherapy and in combination with ezabenlimab, showed preliminary clinical activity, with some patients experiencing stable disease and confirmed partial responses, suggesting potential efficacy in treating advanced tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of the VEGF/Ang-2 inhibitor BI 836880 alone or combined with the anti-programmed cell death protein-1 antibody ezabenlimab in Japanese patients with advanced solid tumors. Yamamoto, N., Koyama, T., Shimizu, T., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2515

An open-label, phase I trial of the SIRPα monoclonal ... Results: At data cut-off (Nov 22, 2024), 21 pts had received BI 770371 monotherapy across 6 dose levels, and 15 pts had received BI 770371 in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05327946

NCT05327946 | A Study in People With Advanced Cancer ... The purpose of this study is to find the highest dose of BI 770371 that people with advanced cancer can tolerate when taken alone or together with a medicine ...

3. boehringer-ingelheim.com boehringer-ingelheim.com/science-innovation/human-health-innovation/new-study-data-sirpa-inhibitors

New study data for SIRPα inhibitors Next generation SIRPα inhibitor BI 770371 was shown to be well tolerated alone and in combination with PD1 inhibitor ezabenlimab in a dose ...

4. ose-immuno.com ose-immuno.com/wp-content/uploads/2023/11/SIRPa-1501.1-data-poster-ESMO-2023-.pdf

Open-label, Phase I dose escalation/expansion trial of the ... (NCT05327946) in patients with advanced solid tumours, BI 770371 ± ezabenlimab was well tolerated. • There were no DLTs during the MTD evaluation period. One ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06806852

NCT06806852 | A Study to Test Whether Treatment With BI ... BI 770371 and pembrolizumab may help the immune system fight cancer. Cetuximab blocks growth signals and may prevent the tumor from growing. Participants are ...

6. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/us/inoncology/our-pipeline/sirpa-antagonist/sirp-results-of-phase1

SIRP Results of Phase I | InOncology SIRPα antagonist (BI 765063) in patients with advanced solid tumors. Phase I safety data. BI 765063 was well-tolerated with no reported DLTs up to the highest ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)02720-5/pdf

monoclonal antibody BI 770371 in patients Based on emerging data a once every 3 weeks schedule in 40mg/kg dose was tested. The primary objectives were to determine the maximum-tolerated dose or ...

8. medinfo.boehringer-ingelheim.com medinfo.boehringer-ingelheim.com/us/research-development/clinical-trials/details/nct05327946

Boehringer Ingelheim USA Medical and Clinical Resources This study is open to adults with advanced cancer (solid tumours). People for whom previous treatment was not successful and for whom no ...

9. delta.larvol.com delta.larvol.com/Products/?ProductId=a7c1443c-6cf8-4ed1-8239-2405462afa19

BI 770371 / Boehringer Ingelheim, OSE Immunotherapeutics ... advanced solid tumors. The MTD of BI 770371 was not reached in either group." Clinical • Combination therapy • Metastases • P1 data • CNS Disorders ...