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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of medicines, BI 1703880 and ezabenlimab, to determine the tolerance levels in people with advanced cancer. These medicines may enhance the immune system's ability to fight cancer. Participants will receive these medicines intravenously over several weeks, allowing researchers to monitor health and any side effects. This trial targets adults with advanced, hard-to-treat solid tumors who have not found success with other treatments. 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 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.

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

Research has shown that ezabenlimab is generally well tolerated by people with various solid tumors, with a safety profile similar to other immune-boosting cancer drugs. In contrast, BI 1703880 is a new treatment undergoing its first tests in humans. Early studies combining BI 1703880 with ezabenlimab suggest potential tumor-fighting benefits, but information about its safety in humans remains limited. This trial aims to determine a safe dose of BI 1703880 that people can tolerate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BI 1703880 and Ezabenlimab for advanced solid tumors because they target cancer cells in a novel way. Unlike most standard treatments, which often rely on chemotherapy to kill rapidly dividing cells, these drugs work by enhancing the immune system's ability to fight cancer. Ezabenlimab is an immune checkpoint inhibitor that helps unleash immune cells against tumors, while BI 1703880 may have a unique role in modulating the tumor environment. This combination could offer a new option where the immune system plays a central role in combating cancer, potentially leading to more effective and lasting responses.

What evidence suggests that BI 1703880 and ezabenlimab could be effective for advanced cancer?

Research suggests that using BI 1703880 with ezabenlimab, as studied in this trial, might help fight cancer by strengthening the immune system. Animal studies have shown that BI 1703880 can kill cancer cells, which is promising for its use in people. Early data from studies indicate that combining BI 1703880 with ezabenlimab seems safe and may help treat advanced cancers. Ezabenlimab helps the immune system find and attack cancer cells. Although these findings are preliminary, they suggest that this combination could be effective against advanced solid tumors. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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.

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

My kidney function, measured by eGFR, is normal or near normal.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39817655/

Open-label, phase Ia study of STING agonist BI 1703880 plus ... This study is evaluating BI 1703880 for patients with advanced cancers based on its ability to destroy cancer cells in animal studies.

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02585-7/fulltext

1007P Systemic STING agonist BI 1703880 plus ... Here, we present initial data, including safety, efficacy, pharmacokinetics, and pharmacodynamics, for BI 1703880 plus ezabenlimab (anti-PD-1 antibody) in pts ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05471856

NCT05471856 | A Study to Test How Different Doses of BI ... 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.

4. tandfonline.com tandfonline.com/doi/full/10.1080/14796694.2024.2441107

Open-label, phase Ia study of STING agonist BI 1703880 ... This study is evaluating BI 1703880 for patients with advanced cancers based on its ability to destroy cancer cells in animal studies.

5. scientiasalut.gencat.cat scientiasalut.gencat.cat/bitstream/handle/11351/12812/open-label-phase_ia-study-sting-agonist-bi-1703880-plus-ezabenlimab-patients-advanced-solid-tumors-2025.pdf?sequence=1&isAllowed=y

Open-label, phase Ia study of STING agonist BI 1703880 ... This study is evaluating the STING agonist BI 1703880 in combi- nation with the anti-PD-1 antibody ezabenlimab in adult patients with advanced ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02585-7/abstract

1007P Systemic STING agonist BI 1703880 plus ezabenlimab in ... BI 1703880 is a novel, systemically administered, next-generation STING agonist with proven antitumor activity in vivo.