BI 907828 + Ezabenlimab (+/- BI 754111) for Advanced Cancer

Not currently recruiting at 32 trial locations

Overseen By Additional US locations available on demand. Please contact for options.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must not be taking: Immunosuppressive corticosteroids

Disqualifiers: Symptomatic brain metastases, Active bleeding, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of two medicines, brigimadlin (also known as BI 907828) and ezabenlimab, can shrink tumors in individuals with certain advanced cancers, such as soft tissue sarcoma and advanced lung, stomach, bladder, or bile duct cancer. Brigimadlin blocks a protein that aids cancer growth, while ezabenlimab enhances the immune system's ability to fight cancer. Individuals whose cancer has progressed or returned after standard treatments, or who lack proven treatment options, might be suitable candidates. Participants will take tablets and receive infusions every three weeks, with doctors monitoring tumor size and any health issues. 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, it mentions that patients who must or wish to continue taking restricted medications or any drug likely to interfere with the trial cannot participate. It's best to discuss your current medications with the trial team to see if they are allowed.

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

Research has shown that the combination of brigimadlin (BI 907828) and ezabenlimab is generally safe. In studies involving patients with advanced biliary tract cancer (BTC), this combination helped shrink tumors and was mostly well-tolerated. In one study, out of eight patients, five experienced partial tumor shrinkage, and two had stable disease, indicating positive effects without severe side effects.

The early phase of the study aimed to find the highest dose of brigimadlin that could be safely used with ezabenlimab. Researchers closely monitored safety and adjusted doses to prevent serious side effects. The data suggests the treatment is reasonably safe, but it is important to remember this is based on early research. Participants needed to tolerate the treatment to continue in the study, indicating it was manageable for those who stayed.

Additionally, a third drug, BI 754111, was discontinued because another study showed it didn't provide extra benefits, not due to safety issues. This decision was based on efficacy, not safety, indicating minimal safety concerns.

Overall, the evidence so far supports that the combination of brigimadlin and ezabenlimab is generally safe, although more research will help confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BI 907828 and Ezabenlimab for advanced cancer because these treatments work differently from current options. While most cancer therapies focus on directly killing cancer cells, BI 907828 targets a specific protein called MDM2, which is involved in tumor growth, potentially stopping cancer cells from multiplying. Ezabenlimab, on the other hand, is an immune checkpoint inhibitor that unleashes the body's immune system to attack cancer cells more effectively. Some treatment arms also include BI 754111, which could enhance the immune response even further. These innovative mechanisms offer hope for more effective treatments against advanced cancers.

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

Research has shown that brigimadlin (BI 907828), an MDM2 inhibitor, may shrink tumors in people with advanced cancers, particularly those with a specific type of biliary tract cancer. This drug targets a protein that prevents cancer cell growth. In this trial, some participants will receive brigimadlin combined with ezabenlimab, a drug that enhances the immune system's ability to fight cancer. Studies have found that these two drugs together can produce anti-tumor effects. Another arm of this trial will add a third drug, BI 754111, to the combination of brigimadlin and ezabenlimab. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

Adults with various advanced cancers, including specific soft tissue sarcomas and lung, stomach, bladder or bile duct cancers. Participants must be over 18, have acceptable blood counts and organ function, not be pregnant or nursing, use reliable birth control if applicable, and cannot have other active malignancies or severe health conditions that could affect trial participation.

Inclusion Criteria

I am using two reliable birth control methods if I can have children.

I am fully active or can carry out light work.

I had anti-PD-1/PD-L1 treatment, but my last dose was over 28 days ago.

Exclusion Criteria

I still have side effects from my last treatment.

I have not had any other cancer in the last 3 years.

I am currently experiencing bleeding or have a high risk of bleeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of brigimadlin in combination with ezabenlimab to determine the maximum tolerated dose

Varies

Every 3 weeks

Dose Expansion

Participants receive the determined dose of brigimadlin and ezabenlimab to evaluate tumor response

Up to 2 years

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• BI 907828
• Ezabenlimab

Trial Overview The study tests different doses of BI 907828 combined with ezabenlimab in patients with advanced cancer. The first part determines the highest tolerable dose; the second part assesses tumor shrinkage using this dose combination. Treatment includes infusions of ezabenlimab every three weeks alongside oral BI 907828 tablets.

How Is the Trial Designed?

Group I: Dose Expansion - Cohort 2 - BI 907828 + ezabenlimab Experimental Treatment 2 Interventions

Group II: Dose Expansion - Cohort 1 BI 907828 + ezabenlimab Experimental Treatment 2 Interventions

Group III: Dose Escalation - BI 907828 + ezabenlimab + BI 754111 Experimental Treatment 3 Interventions

All neoplasms

Group IV: Dose Escalation - BI 907828 + ezabenlimab Experimental Treatment 2 Interventions

All neoplasms

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

Nivolumab combined with ipilimumab demonstrated significantly better overall survival compared to BRAF + MEK inhibitors, with hazard ratios indicating a 36% to 44% reduction in the risk of death after 12 months.

While nivolumab + ipilimumab had improved survival outcomes, it also resulted in a higher rate of grade 3/4 adverse events (54.1%) compared to dabrafenib + trametinib (31.6%) and similar rates to vemurafenib + cobimetinib (59.5%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of combination immunotherapy and targeted therapy in the treatment of BRAF-mutant advanced melanoma: a matching-adjusted indirect comparison. Atkins, MB., Tarhini, A., Rael, M., et al.[2020]

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 ARTEMIS study shows that combining the VEGF inhibitor bevacizumab with the EGFR inhibitor erlotinib significantly improves progression-free survival in patients with EGFR mutant non-small-cell lung cancer by over 6 months.

Patients with brain metastases and the EGFR L858R mutation experienced even greater benefits, highlighting the importance of personalized treatment strategies in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ARTEMIS highlights VEGF inhibitors as effective partners for EGFR TKIs in EGFR mutant NSCLC. Le, X., Nilsson, MB., Robichaux, JP., 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]

The combination of encorafenib (ENC) and binimetinib (BIN) was found to be cost-effective compared to cobimetinib (COB) and vemurafenib (VEM) only at a very high willingness-to-pay threshold of $573,000 per quality-adjusted life year (QALY).

The combination of dabrafenib (DAB) and trametinib (TRA) was determined to be the most optimal treatment option for BRAF-mutated advanced melanoma, dominating the COB + VEM combination in terms of cost-effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic Evaluation of Three BRAF + MEK Inhibitors for the Treatment of Advanced Unresectable Melanoma With BRAF Mutation From a US Payer Perspective. Halloush, S., Alkhatib, NS., Almutairi, AR., et al.[2023]

In a study of 122 patients with advanced non-small cell lung cancer (NSCLC) and EGFR exon 20 insertions, first-line chemotherapy combined with angiogenesis inhibitors showed a significantly better objective response rate (38.1% vs. 18.2%) and longer progression-free survival (7.73 months vs. 5.93 months) compared to chemotherapy alone.

The combination of chemotherapy with immune checkpoint inhibitors did not provide a survival benefit over chemotherapy alone, suggesting that intrinsic resistance mechanisms, possibly linked to the activation of the PI3K/AKT signaling pathway, may limit the effectiveness of immunotherapy in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line immunotherapy or angiogenesis inhibitor combined with chemotherapy for advanced non-small cell lung cancer with EGFR exon 20 insertions: Real-world evidence from China. Yang, G., Yang, Y., Liu, R., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.487

Efficacy and safety of brigimadlin (BI 907828), an MDM2– ... 487. Background: Outcomes remain poor for pts treated with standard-of-care chemotherapy for advanced biliary tract cancer (BTC).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03964233

NCT03964233 | A Study in Patients With Different Types of ... The participants get a combination of 2 medicines called brigimadlin (also called BI 907828) and ezabenlimab (also called BI 754091). Brigimadlin is a so-called ...

3. medinfo.boehringer-ingelheim.com medinfo.boehringer-ingelheim.com/us/sites/default/files/2022-11/ph%20iaib%20study%20of%20bi%20907828%20in%20combination%20with%20immune%20checkpoint%20inhibitor%28s%29%20in%20solid%20tumors.pdf

A Phase Ia/Ib, dose-escalation/expansion study of BI ... • We present results from patients enrolled in the Phase Ia part who received BI ... BI 907828 in combination with ezabenlimab where preliminary efficacy has been ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38567193/

Efficacy and Safety of the MDM2-p53 Antagonist ... Brigimadlin demonstrated anti-tumor activity in patients with advanced MDM2-amplified BTC, and warrants further investigation.

5. ccanewsonline.com ccanewsonline.com/issues/2023/march-2023-vol-4-no-1/mdm2-p53-antagonist-bi-907828

MDM2-p53 Antagonist BI 907828 Demonstrated Promising ... The novel MDM2-p53 antagonist BI 907828 is being investigated as a first-line treatment in patients with advanced biliary tract cancer.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.543

Efficacy and safety of the MDM2–p53 antagonist BI 907828 ... The MDM2–p53 antagonist BI 907828 has shown a manageable safety profile and encouraging preliminary efficacy in patients with BTC, with 5 PRs and 2 SD in 8 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10986405/

Efficacy and Safety of the MDM2–p53 Antagonist Brigimadlin ... Brigimadlin demonstrated anti-tumor activity in patients with advanced MDM2-amplified BTC, and warrants further investigation.

8. ccanewsonline.com ccanewsonline.com/issues/2024/march-2024-vol-5-no-1/efficacy-and-safety-of-brigimadlin-bi-907828-in-patients-with-advanced-btc-data-from-2-phase-1a-1b-dose-escalation-expansion-trials

Efficacy and Safety of Brigimadlin (BI 907828) in Patients ... The safety and efficacy of brigimadlin are currently being assessed in advanced solid tumors in 2 phase 1a/1b dose-escalation/expansion trials, both as a ...