BI 1831169 + Ezabenlimab for Advanced Cancers

Recruiting at 51 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must not be taking: Interferon, Immunotherapy, Tamoxifen

Disqualifiers: Brain metastases, HIV, Autoimmune, others

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

Compensation: Varies

Number of Visits: 6

190 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine, BI 1831169, for individuals with advanced cancers that have spread and cannot be surgically removed. The goal is to determine the highest dose patients can tolerate, both alone and in combination with a checkpoint inhibitor, Ezabenlimab, which aids the immune system in fighting cancer. In Part 1, participants receive only BI 1831169, while Part 2 involves the combination treatment. The trial seeks participants who have not responded to other treatments and have tumors accessible for injections or biopsies. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

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.

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

Research shows that BI 1831169, an experimental virus treatment, is undergoing safety testing in people with advanced cancers. Early studies suggest it targets and destroys cancer cells while sparing healthy ones. Although still in early human testing, initial safety results indicate it is generally well-tolerated.

Ezabenlimab, another treatment in this trial, is a type of immunotherapy known as a checkpoint inhibitor. Research has shown that ezabenlimab is usually well-tolerated, with side effects similar to other drugs in its category. These side effects can include mild to moderate issues like tiredness or skin rash, which can be managed.

The combination of BI 1831169 and ezabenlimab is under study to assess their joint effectiveness against cancer. While detailed safety information for the combination is still being gathered, early findings do not reveal any unexpected safety concerns beyond what is known for each treatment alone. Doctors closely monitor trial participants for any health issues that might occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BI 1831169 combined with Ezabenlimab because these treatments bring a fresh approach to fighting advanced cancers. Unlike traditional therapies, which often rely on broad mechanisms like chemotherapy or radiation, these drugs target specific pathways involved in cancer cell growth and survival. BI 1831169 works by inhibiting a key enzyme that cancer cells rely on, while Ezabenlimab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. Together, they offer a potentially powerful combination that might overcome resistance to existing treatments and provide new hope for patients with difficult-to-treat cancers.

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

Research has shown that BI 1831169, a virus targeting cancer cells, has shown promise in lab studies. It effectively destroys cancer cells and triggers the immune system to fight tumors. In this trial, some participants will receive BI 1831169 as monotherapy. Additionally, ezabenlimab, a drug that aids the immune system in attacking cancer, has shown potential in treating advanced solid tumors by boosting natural defenses. Other participants will receive a combination of BI 1831169 and ezabenlimab. Together, these treatments aim to directly target cancer cells and enhance the immune system's ability to fight cancer. Early study results suggest this combination may be effective for advanced cancers, but further research is needed to confirm these findings in humans. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• BI 1831169
• Ezabenlimab

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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

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]

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 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]

In a study involving 137 patients with advanced solid tumors, the combination of lenvatinib and pembrolizumab showed a manageable safety profile, with common side effects including fatigue, diarrhea, and hypertension.

The treatment demonstrated promising antitumor activity, with objective response rates at week 24 ranging from 25% to 63% across different cancer types, indicating its potential effectiveness in various advanced cancers.

NCBI (Pubmed)

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. Taylor, MH., Lee, CH., Makker, V., et al.[2021]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35699077/

Phase I study of VSV-GP (BI 1831169) as monotherapy or ... This first-in-human study will investigate VSV-GP on its own and in combination with an ICI called ezabenlimab for the treatment of late-stage cancer.

2. tandfonline.com tandfonline.com/doi/full/10.2217/fon-2022-0439

Phase I study of VSV-GP (BI 1831169) as monotherapy or ... This first-in-human study will investigate VSV-GP on its own and in combination with an ICI called ezabenlimab for the treatment of late-stage cancer.

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02605-X/fulltext

1027P First results for intravenous (IV) VSV-GP (BI ... VSV-GP (BI 1831169), a selective oncolytic virus, generates potent cancer cell oncolysis in vitro and initiates adaptive antitumor immunity in vivo.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05155332

NCT05155332 | A Study to Test Different Doses of BI ... The purpose of this study is to find the highest dose of a medicine called BI 1831169 that people with advanced cancer can tolerate when taken with or without a ...

5. content.boehringer-ingelheim.com content.boehringer-ingelheim.com/DAM/7cd755fc-b2aa-4ebd-a4f7-b1f0008579f4/congress%20hub%20esmo%202024%20poster%201027p%20oliva%20%28vsv-gp%29.pdf

First results for IV VSV-GP (BI 1831169) in patients with ... First results for IV VSV-GP (BI 1831169) in patients with advanced solid tumors from the 1456-0001 study ... antibody ezabenlimab (Part 2), and to assess ...

6. content.boehringer-ingelheim.com content.boehringer-ingelheim.com/DAM/3de0bd33-b87f-4c19-abdf-b0f500dc07b4/vsv-gp__esmo%20io_poster_final.pdf

First-in-human results from a Phase I dose-escalation study ... ... VSV-GP (BI 1831169) in patients with advanced solid tumors. 459. Stephane ... • First safety data from the 1456-0001 study suggest that VSV-GP is well ...

7. oncology-central.com oncology-central.com/phase-i-study-of-vsv-gp-bi-1831169-as-monotherapy-or-combined-with-ezabenlimab-in-advanced-and-refractory-solid-tumors/

Phase I study of VSV-GP (BI 1831169) as monotherapy or ... Here, we describe the background and design of this study in progress which aims to find out if VSV-GP alone or in combination with ezabenlimab ...