BI 1831169 + Ezabenlimab for Advanced Cancers

Recruiting in Palo Alto (17 mi)

+37 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: Interferon, Immunotherapy, Tamoxifen

Disqualifiers: Brain metastases, HIV, Autoimmune, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is for adults with advanced cancers that can be injected and who have no other treatment options. It tests a new medicine, BI 1831169, alone and with another medicine, ezabenlimab, to see if they can help the immune system fight cancer. The study aims to find the highest safe doses and check if the medicines can shrink tumors.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot use interferon, immunotherapy agents, or tamoxifen within 30 days before or during the treatment phase.

What data supports the effectiveness of the drug BI 1831169 + Ezabenlimab for advanced cancers?

The combination of drugs similar to BI 1831169 and Ezabenlimab, such as lenvatinib and pembrolizumab, has shown promise in treating advanced solid tumors by enhancing the immune system's ability to fight cancer. This suggests that combining drugs that target blood vessel growth and immune checkpoints could be effective in treating advanced cancers. ^{1 2 3 4 5}

How is the drug BI 1831169 + Ezabenlimab unique for advanced cancers?

The combination of BI 1831169 and Ezabenlimab is unique because it targets both the vascular endothelial growth factor (VEGF) and angiopoietin-2, along with inhibiting programmed death protein-1 (PD-1), which may enhance its effectiveness against advanced cancers compared to treatments targeting only one of these pathways. ^{1 6 7 8 9}

Research Team

Eligibility Criteria

Adults with advanced solid tumors that haven't responded to previous treatments or have no other options can join. They need at least one tumor suitable for injection and biopsy, be over 18 years old, in good health for trial procedures, have a performance status of 0 or 1, and proper organ function. Patients must not have had recent radiation to the target lesions or suffer from conditions like uncontrolled HIV/AIDS.

Inclusion Criteria

I have tumors that can be easily reached for treatment or biopsy.

Total bilirubin ≤ 1.5 x ULN, except for patients with Gilbert's syndrome: total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN

I have tried all known treatments for my cancer or cannot use them, and they haven't worked.

Exclusion Criteria

I do not have an active infection needing treatment when the trial starts.

I have not had radiotherapy in the last 4 weeks, except for short-term pain relief or to prevent bone fractures.

I am not on antiretroviral therapy.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1 (Monotherapy)

Participants receive BI 1831169 alone for up to 3 months

12 weeks

Every 3 weeks, some visits include an overnight stay

Treatment Part 2 (Combination Therapy)

Participants receive BI 1831169 in combination with a checkpoint inhibitor for up to 1 year

12 months

Every 3 weeks, some visits include an overnight stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

Treatment Details

Interventions

• BI 1831169 (Monoclonal Antibodies)
• Ezabenlimab (Monoclonal Antibodies)

Trial Overview The study is testing BI 1831169 alone and combined with ezabenlimab on different types of advanced cancers. Part one determines the highest tolerable dose of BI 1831169; part two does the same for its combination with ezabenlimab. Treatments are given every three weeks via injection into the tumor or infusion into a vein.

Participant Groups

Group I: Part 2 (Combination therapy): Arm G Experimental Treatment 2 Interventions

Group II: Part 2 (Combination therapy): Arm F Experimental Treatment 2 Interventions

Arm F: i.t.+i.v. administration

Group III: Part 2 (Combination therapy): Arm E Experimental Treatment 2 Interventions

Arm E: Intravenous (i.v.) administration

Group IV: Part 2 (Combination therapy): Arm D Experimental Treatment 2 Interventions

Arm D: Intratumoral (i.t.) administration

Group V: Part 1 (Monotherapy): Arm C Experimental Treatment 1 Intervention

Arm C: i.t.+i.v. administration

Group VI: Part 1 (Monotherapy): Arm B Experimental Treatment 1 Intervention

Arm B: Intravenous (i.v.) administration

Group VII: Part 1 (Monotherapy): Arm A Experimental Treatment 1 Intervention

Arm A: Intratumoral (i.t.) administration

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Banner MD Anderson Cancer Center-Gilbert-55251 Gilbert, AZ

John Wayne Cancer Institute Santa Monica, CA

University of Arizona Tucson, AZ

University of Colorado Denver Aurora, CO

More Trial Locations

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Findings from Research

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 nivolumab and erlotinib was found to be tolerable in patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC), with treatment-related grade 3 toxicities occurring in only five out of twenty patients, and no severe grade 4 toxicities reported.

Among the TKI-treated patients, the objective response rate was 15%, with some patients experiencing durable responses lasting up to 38.2 months, indicating potential efficacy of this combination therapy in managing advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC. Gettinger, S., Hellmann, MD., Chow, LQM., et al.[2019]

In a study of 48 patients with recurrent endometrial cancer treated with pembrolizumab and lenvatinib, the best objective response rate was 23.8%, indicating a lower effectiveness compared to clinical trial results.

The treatment was associated with notable side effects, with 56.2% of patients requiring a dose reduction of lenvatinib and 16.7% discontinuing treatment due to adverse events, highlighting the importance of monitoring for safety in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of pembrolizumab and lenvatinib in recurrent endometrial cancer: A multicenter study in Korea. Kim, J., Noh, JJ., Lee, TK., et al.[2022]

BRAF mutations activate the Ras-Raf-MEK-ERK signaling pathway and are common in various cancers, with combined BRAF and MEK inhibitors showing improved survival rates in cutaneous malignant melanoma.

This report highlights the successful use of the BRAF inhibitor vemurafenib combined with the MEK inhibitor cobimetinib in a young patient with BRAF V600E-positive multiple myeloma, leading to a rapid and sustained response despite previous treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vemurafenib in combination with cobimetinib in relapsed and refractory extramedullary multiple myeloma harboring the BRAF V600E mutation. Mey, UJM., Renner, C., von Moos, R.[2019]

BRAF V600E mutations occur in 3%-10% of multiple myeloma patients and are linked to more aggressive disease and shorter survival rates.

A combination treatment of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib showed a very good partial response in a patient with refractory multiple myeloma, suggesting a potential new therapeutic strategy for this mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Partial response to dabrafenib and trametinib in relapsed BRAF V600E-Mutated multiple myeloma and possible mechanisms of resistance. Ernst, T., Aebi, S., Zander, A., et al.[2022]

In a study of 25 treatment-naive patients with advanced nonsquamous non-small cell lung cancer (NSCLC), the combination of camrelizumab and low-dose apatinib resulted in a 40% objective response rate and a high disease control rate of 92%.

The treatment demonstrated promising efficacy with a median progression-free survival of 9.6 months and acceptable safety, with the most common serious side effects being increased liver enzymes, indicating that this combination could be a viable frontline therapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Camrelizumab Plus Apatinib in Treatment-Naive Patients With Advanced Nonsquamous NSCLC: A Multicenter, Open-Label, Single-Arm, Phase 2 Trial. Ren, S., He, J., Fang, Y., et al.[2022]

The combination of vibostolimab and pembrolizumab is well tolerated by patients, indicating a favorable safety profile for this treatment regimen.

This combination therapy demonstrates antitumor activity, suggesting it may be an effective option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

References

1. 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]

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

Phase IB study of ziv-aflibercept plus pembrolizumab in patients with advanced solid tumors. [2022]

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

Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC. [2019]

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

Real-world experience of pembrolizumab and lenvatinib in recurrent endometrial cancer: A multicenter study in Korea. [2022]

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

Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Vemurafenib in combination with cobimetinib in relapsed and refractory extramedullary multiple myeloma harboring the BRAF V600E mutation. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Partial response to dabrafenib and trametinib in relapsed BRAF V600E-Mutated multiple myeloma and possible mechanisms of resistance. [2022]

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

Camrelizumab Plus Apatinib in Treatment-Naive Patients With Advanced Nonsquamous NSCLC: A Multicenter, Open-Label, Single-Arm, Phase 2 Trial. [2022]

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

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]