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

Recruiting at 30 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

120 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug BI 907828 + Ezabenlimab (+/- BI 754111) for advanced cancer?

The combination of anti-angiogenic agents (which block the growth of new blood vessels that tumors need to grow) with immune checkpoint inhibitors (which help the immune system recognize and attack cancer cells) has shown potential in overcoming immune suppression in cancer treatment, as seen in studies with similar drug combinations. ^{1 2 3 4 5}

What makes the drug BI 907828 + Ezabenlimab unique for advanced cancer?

This treatment combines BI 907828, a novel drug, with Ezabenlimab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. The combination may offer a new approach by potentially enhancing the immune response against tumors, which is different from standard treatments that often focus on either chemotherapy or single-agent immunotherapy. ^{1 2 3 6 7}

What is the purpose of this trial?

This study has 2 parts. The first part of the study is done. The first part was open to adults with different types of advanced cancer (solid tumors). The second part is open to people with specific types of soft tissue sarcoma, advanced lung cancer, and cancer in the stomach, bladder or bile ducts. 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 MDM2 inhibitor that is being developed to treat cancer. Ezabenlimab is an antibody that may help the immune system fight cancer (immune checkpoint inhibitor). When the study started, some participants got a third medicine called BI 754111 in addition. Treatment with BI 754111 was stopped because data from another study showed no additional effect of BI 754111. The purpose of the first part of the study was to find out the highest dose of brigimadlin that the participants could tolerate in combination with ezabenlimab. This dose is used in the second part of the study. The purpose of the second part is to see whether the combination of brigimadlin with ezabenlimab is able to make tumors shrink. The participants are in the study as long as they benefit from treatment and can tolerate it. Ezabenlimab treatment is limited to 2 years. During this time, they get infusions of ezabenlimab, and take tablets with brigimadlin every 3 weeks. The doctors check how many participants have health problems during the study. The doctors also monitor the size of the tumor.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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]

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]

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]

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]

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]

References

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

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

2. Ireland pubmed.ncbi.nlm.nih.gov

Anlotinib combined with anti-PD-1 antibody, camrelizumab for advanced NSCLCs after multiple lines treatment: An open-label, dose escalation and expansion study. [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. United States 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. [2023]

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

ARTEMIS highlights VEGF inhibitors as effective partners for EGFR TKIs in EGFR mutant NSCLC. [2021]

6. England 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. [2020]

7. United States 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. [2023]