BI 770371 + Ezabenlimab for Advanced Solid Tumors

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

36 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination BI 770371 and ezabenlimab for advanced solid tumors?

Research on similar drug combinations, like lenvatinib plus pembrolizumab, shows that blocking both VEGF (a protein that helps tumors grow blood vessels) and immune checkpoints can enhance the body's immune response to fight tumors. This suggests that combining BI 770371, which may have similar effects, with ezabenlimab could potentially be effective for treating advanced solid tumors. ^{1 2 3 4 5}

What is known about the safety of PD-1/PD-L1 blocking drugs like ezabenlimab?

PD-1/PD-L1 blocking drugs, which include ezabenlimab, generally have a manageable safety profile, making them suitable for outpatient use. Most side effects are mild to moderate, but some patients may experience severe reactions, which are managed with close monitoring and early treatment. ^{2 6 7 8 9}

What makes the drug BI 770371 + Ezabenlimab unique for advanced solid tumors?

This treatment combines BI 770371, which targets specific proteins involved in blood vessel growth, with ezabenlimab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. This combination approach is novel because it targets both the tumor's blood supply and the immune system, potentially offering a more comprehensive treatment strategy for advanced solid tumors. ^{2 4 5 10 11}

What is the purpose of this trial?

This trial is for adults with advanced cancer who have no other treatment options. It tests BI 770371 alone or with ezabenlimab, which help the immune system fight cancer. The treatments are given periodically through a drip.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

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Anlotinib combined with anti-PD-1 antibody, camrelizumab for advanced NSCLCs after multiple lines treatment: An open-label, dose escalation and expansion study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Safety, recommended dose, efficacy and immune correlates for nintedanib in combination with pembrolizumab in patients with advanced cancers. [2022]

3. England pubmed.ncbi.nlm.nih.gov

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. [2021]

4. Germany 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. [2023]

5. England 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. [2023]

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

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

7. Spain 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. [2021]

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Effect of concomitant medications with immune-modulatory properties on the outcomes of patients with advanced cancer treated with immune checkpoint inhibitors: development and validation of a novel prognostic index. [2021]

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Antagonists of PD-1 and PD-L1 in Cancer Treatment. [2022]

10. Ireland 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). [2023]

11. United States 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. [2017]