BI 1703880 + Ezabenlimab for Advanced Solid Tumors

Recruiting at 13 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must not be taking: Sting agonists, Immunosuppressives

Disqualifiers: Autoimmune disease, Pneumonitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1-2 years

66 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is open to adults with different types of advanced cancer. People can take part if previous treatment was not successful, or no treatment exists. The purpose of this study is to find the highest dose of a medicine called BI 1703880 that people with advanced cancer can tolerate when taken together with ezabenlimab. BI 1703880 and ezabenlimab are medicines that may help the immune system fight cancer. In this study, BI 1703880 is given to people for the first time. Participants get BI 1703880 and ezabenlimab as infusions into a vein. During the first 6 weeks, they get BI 1703880 once a week. Later, they get BI 1703880 every 3 weeks. After the first 3 weeks, they get ezabenlimab in addition every 3 weeks. Participants can get BI 1703880 for up to 1 year and ezabenlimab for up to 2 years as long as they benefit from treatment and can tolerate it. During this time, they visit the study site regularly. At these visits, the doctors check participants' health and take note of any unwanted effects.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot have had any investigational or antitumor treatment within 4 weeks before starting the trial, and you should not be on certain immunosuppressive therapies.

What data supports the effectiveness of the drug BI 1703880 + Ezabenlimab for advanced solid tumors?

Research shows that combining drugs targeting blood vessel growth (like BI 836880) with immune system boosters (like ezabenlimab) can help fight advanced solid tumors. Similar combinations have shown promise in other studies, suggesting potential benefits for this drug combination. ^{1 2 3 4 5}

What safety data exists for BI 1703880 and Ezabenlimab in humans?

A study on BI 836880 combined with ezabenlimab in Japanese patients with advanced solid tumors aimed to find the maximum tolerated dose, indicating ongoing research into their safety. PD-1/PD-L1 blocking drugs, like ezabenlimab, generally have a manageable safety profile, making them suitable for outpatient use. ^{2 3 4 6 7}

What makes the drug combination of BI 1703880 and Ezabenlimab unique for treating advanced solid tumors?

The combination of BI 1703880 and Ezabenlimab is unique because it targets both vascular endothelial growth factor (VEGF) and angiopoietin-2, along with inhibiting programmed death protein-1 (PD-1), potentially offering a dual mechanism to combat tumor growth and enhance immune response, which is different from standard treatments that typically target only one pathway. ^{3 5 8 9 10}

Eligibility Criteria

Adults with advanced, hard-to-treat cancers can join this trial if previous treatments failed or aren't available. They need at least one measurable tumor and must be healthy enough for biopsies and other procedures. An ECOG score of 0-1 is required, indicating they are fully active or restricted in physically strenuous activity but ambulatory.

Inclusion Criteria

My liver function tests are within the required range.

I am 18 years old or older, or meet the legal age of consent for my country.

Haemoglobin ≥ 90 g/L (≥ 9.0 g/dL, ≥ 5.6 mmol/L)

Exclusion Criteria

You have had an allergic reaction or are sensitive to any components of the study drug.

I am not on high-dose steroids or medications that significantly weaken my immune system.

I have lasting side effects from past treatments, but they are mild except for hair loss, dry mouth, or hormone issues.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BI 1703880 once a week for the first 6 weeks, then every 3 weeks, with ezabenlimab added every 3 weeks after the first 3 weeks

1-2 years

Regular visits to the study site

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BI 1703880
• Ezabenlimab

Trial Overview The trial tests the highest tolerable dose of BI 1703880 combined with Ezabenlimab, both immune system-boosting drugs given via vein infusion. Initially, BI 1703880 is weekly for six weeks then every three weeks; Ezabenlimab starts after three weeks and continues every three weeks up to two years.

Participant Groups

Group I: BI 1703880 (Cycle 1) then BI 1703880 + ezabenlimab (Cycle 2 onwards) Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Findings from Research

In a phase IB study involving 33 patients with advanced solid tumors, the combination of ziv-aflibercept and pembrolizumab was found to have an acceptable safety profile, with no dose-limiting toxicities at the maximum tolerated dose of ziv-aflibercept 4 mg/kg and pembrolizumab 2 mg/kg every 2 weeks.

The overall response rate was 16.7%, with notable complete responses in melanoma and partial responses in other cancers, indicating potential antitumor activity of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IB study of ziv-aflibercept plus pembrolizumab in patients with advanced solid tumors. Rahma, OE., Tyan, K., Giobbie-Hurder, A., 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]

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]

The combination of lenalidomide and temsirolimus was well tolerated in a phase I study involving 43 patients with advanced cancers, with no dose-limiting toxicities observed, although 72% experienced reversible grade 3-4 hematologic toxicities.

Clinical benefits were noted, with 2.5% of patients achieving a partial response and 48% having stable disease, particularly in soft tissue sarcoma and adenoid cystic carcinoma, leading to a median overall survival of 7.8 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical trial of lenalidomide in combination with temsirolimus in patients with advanced cancer. Ganesan, P., Piha-Paul, S., Naing, A., et al.[2021]

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]

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]

Dostarlimab, a PD-1 inhibitor, shows promising clinical activity and an acceptable safety profile in patients with recurrent endometrial cancer, especially in those with the microsatellite instability-hypermutated/DNA mismatch repair-deficient subtype.

Research indicates that immune checkpoint inhibitors like dostarlimab may be more effective in specific molecular subgroups of endometrial cancer, highlighting the importance of personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab in the treatment of recurrent or primary advanced endometrial cancer. Kasherman, L., Ahrari, S., Lheureux, S.[2022]

This phase I/II clinical trial is investigating the safety and efficacy of a combination treatment involving selumetinib, tremelimumab, and durvalumab in 40 patients with previously treated, unresectable non-small-cell lung cancer (NSCLC).

The study aims to determine the maximum tolerated dose and progression-free survival, while also exploring biomarkers of response and resistance, which could help tailor future treatments for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Trial of Immunotherapy With Durvalumab and Tremelimumab With Continuous or Intermittent MEK Inhibitor Selumetinib in NSCLC: Early Trial Report. Gaudreau, PO., Lee, JJ., Heymach, JV., et al.[2021]

Immune-checkpoint inhibitors like pembrolizumab have significantly advanced the treatment of non-small cell lung cancer (NSCLC), showing durable responses in patients with advanced disease, especially those with high PDL1 expression.

Pembrolizumab has been approved by the FDA for treatment-naïve metastatic NSCLC with ≥50% PDL1 expression and for patients with ≥1% PDL1 expression after prior chemotherapy, indicating its efficacy and potential as a personalized treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New PDL1 inhibitors for non-small cell lung cancer: focus on pembrolizumab. Bylicki, O., Paleiron, N., Rousseau-Bussac, G., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase IB study of ziv-aflibercept plus pembrolizumab in patients with advanced solid tumors. [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. 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]

4. 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]

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

Phase I clinical trial of lenalidomide in combination with temsirolimus in patients with advanced cancer. [2021]

6. 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]

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

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

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

Dostarlimab in the treatment of recurrent or primary advanced endometrial cancer. [2022]

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

Phase I/II Trial of Immunotherapy With Durvalumab and Tremelimumab With Continuous or Intermittent MEK Inhibitor Selumetinib in NSCLC: Early Trial Report. [2021]

10. New Zealand pubmed.ncbi.nlm.nih.gov

New PDL1 inhibitors for non-small cell lung cancer: focus on pembrolizumab. [2023]