Bexmarilimab + Standard Care for Acute Myeloid Leukemia

(BEXMAB Trial)

Not currently recruiting at 10 trial locations

Overseen By Patient Enrollment Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Faron Pharmaceuticals Ltd

Must be taking: Azacitidine, Venetoclax

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: APL, Auto-immune disorders, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new drug, bexmarilimab (an anti-CLEVER-1 antibody), combined with standard treatments for certain blood cancers. The focus is on patients with myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML). The researchers aim to determine the optimal dose of bexmarilimab and its effectiveness when paired with other common cancer drugs. Prospective participants typically have a confirmed diagnosis of one of these conditions, especially if previous treatments have failed. As a Phase 1 trial, the research seeks to understand how the treatment works in people, offering participants a chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you require certain treatments like systemic corticosteroids or if you have had recent chemotherapy or immunotherapy.

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

Research has shown that bexmarilimab, when combined with azacitidine, has a manageable safety profile, with side effects similar to those expected from azacitidine alone. In earlier studies, patients tolerated this combination well, with encouraging results and no unexpected side effects.

Additionally, research suggests that combining bexmarilimab with venetoclax and standard care is also safe. Although specific side effect details are not provided, this combination is being tested in an early-stage trial to ensure patient tolerance.

These studies are in the early stages, focusing on safety before larger trials. For those considering joining a trial, this information indicates that the treatment combinations are being closely monitored for safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for acute myeloid leukemia (AML) because they introduce a novel approach by combining bexmarilimab with standard care options like azacitidine and venetoclax. Unlike existing treatments, bexmarilimab targets a specific immune checkpoint, potentially enhancing the body's immune response against cancer cells. This combination aims to improve patient outcomes, especially for those who have not responded well to traditional therapies or are newly diagnosed but not fit for intensive induction therapy. By leveraging bexmarilimab's unique mechanism of action alongside standard care, there is hope for more effective and faster results in managing AML.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia?

This trial will evaluate the combination of bexmarilimab with standard treatments for patients with myeloid cancers. Research has shown that bexmarilimab can enhance the immune system's ability to fight cancer cells. In this trial, some participants will receive azacitidine, which studies have found can extend the lives of patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Others will receive venetoclax, which has helped many older AML patients achieve remission. Together, these treatments offer promising results for tackling these challenging blood cancers. ^{6 7 8 9 10}

Who Is on the Research Team?

Mika Kontro

Principal Investigator

Helsinki University Central Hospital

Are You a Good Fit for This Trial?

Adults with certain blood cancers like MDS, CMML-2, or AML who have specific risk levels or treatment histories can join. They need good kidney and liver function and a low enough white blood cell count. People with acute promyelocytic leukemia, poor physical status, recent transplants, active autoimmune diseases (with some exceptions), current heavy immunosuppression use, or recent other cancer treatments cannot participate.

Inclusion Criteria

My CMML or MDS did not improve with HMA treatment.

My kidneys are working well.

I have AML and cannot undergo standard treatment, but can take azacitidine-venetoclax.

Exclusion Criteria

I have APL or CMML with a high white blood cell count.

Pregnant or lactating women.

My physical condition limits my daily activities, except if I have newly diagnosed AML and am under 75.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants receive bexmarilimab at increasing dose levels combined with standard of care to identify the maximum tolerated dose

28-day cycle, repeated as necessary

Weekly visits for dose escalation, then bi-weekly

Phase 2 Treatment

Participants receive bexmarilimab at the recommended phase 2 dose combined with standard of care to evaluate safety and preliminary efficacy

28-day cycle, repeated as necessary

Bi-weekly visits

End of Treatment Follow-up

Participants are monitored for safety after the end of treatment

4 weeks

Disease Progression/Survival Follow-up

Participants are monitored for disease progression and survival

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Bexmarilimab
• Venetoclax

Trial Overview The trial is testing Bexmarilimab combined with standard treatments Azacitidine and Venetoclax in patients with specific types of blood cancers. It's in two phases: the first to find the safest dose level of Bexmarilimab and the second to see how well it works at that dose for these conditions.

How Is the Trial Designed?

Group I: Phase 2 - Intermediate/high risk MDS, CMML, MDS/CMML failure to HMA, r/r AML & newly diagnosed AML Experimental Treatment 3 Interventions

Standard of care venetoclax and/or azacitidine as per label plus bexmarilmab

Group II: Phase 1 - Newly diagnosed AML patients non-fit for induction therapy Experimental Treatment 3 Interventions

Standard of care azacitidine and venetoclax as per label; bexmarilimab 4 dose levels Q1W followed by Q2W; 28-day cycle

Group III: Phase 1 - Intermediate/high risk MDS, CMML 10-19%, MDS/CMML failure to HMA, r/r AML Experimental Treatment 2 Interventions

Standard of care azacitidine as per label; bexmarilimab 4 dose levels at once every week (Q1W) followed by once every 2 weeks (Q2W); 28-day cycle

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

Faron Pharmaceuticals Ltd

Lead Sponsor

Trials

9

Recruited

780+

Published Research Related to This Trial

ASP1235, an antibody drug conjugate targeting FLT3, shows promising anti-tumor effects when combined with venetoclax and azacitidine in a preclinical model of acute myeloid leukemia (AML), particularly in THP-1 cells.

The combination treatment demonstrated superior efficacy compared to monotherapy and did not result in significant body weight loss, suggesting a favorable safety profile for this triple therapy in AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-tumor effect of antibody drug conjugate ASP1235 targeting Fms-like tyrosine kinase 3 with venetoclax plus azacitidine in an acute myeloid leukemia xenograft mouse model. Tsuzuki, H., Kawase, T., Nakazawa, T., et al.[2023]

In a phase II trial involving 209 patients with metastatic colorectal cancer, the addition of bevacizumab to fluorouracil and leucovorin (FU/LV) significantly improved median progression-free survival to 9.2 months compared to 5.5 months with placebo, indicating a strong therapeutic benefit.

While bevacizumab treatment was associated with a higher incidence of grade 3 hypertension (16% vs. 3% in the placebo group), this side effect was manageable with medication and did not lead to discontinuation of the treatment, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. Kabbinavar, FF., Schulz, J., McCleod, M., et al.[2022]

In a study of 31 patients with metastatic colorectal cancer who had previously failed chemotherapy, 32.2% showed an objective response to bevacizumab combined with FOLFIRI or FOLFOX, indicating potential efficacy in chemorefractory cases.

The treatment resulted in a median progression-free survival of 9.7 months and an overall survival of 18.4 months, with acceptable tolerance, suggesting that bevacizumab can be a viable option for patients who have not previously received it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab plus FOLFIRI or FOLFOX in chemotherapy-refractory patients with metastatic colorectal cancer: a retrospective study. Lièvre, A., Samalin, E., Mitry, E., et al.[2021]

In a phase 1/2 study involving six Japanese patients aged 60 and older with acute myeloid leukaemia, the combination of venetoclax and azacitidine demonstrated a high response rate, with 83% of patients achieving a response, including three complete remissions.

The treatment was generally well tolerated, with a median overall survival of 15.7 months, although some patients experienced serious adverse events, including grade 3 fungal pneumonia, which required treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. Taniguchi, S., Yamauchi, T., Choi, I., et al.[2021]

In a study of 60 patients with acute myeloid leukemia (AML), the combination of venetoclax and azacitidine (Ven+AZA) demonstrated a high response rate, with 70.8% of previously untreated patients unfit for standard chemotherapy achieving complete remission (CR) or CR with incomplete hematological recovery (CRi) after one cycle.

Ven+AZA was found to be safe and tolerable, with some patients achieving minimal residual disease (MRD) negativity, particularly in those with favorable genetic mutations like NPM1, IDH1/IDH2, and TP53, indicating its potential effectiveness in specific patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience]. Yu, WJ., Jia, JS., Wang, J., et al.[2022]

In a study of 198 Chinese patients with advanced non-small cell lung cancer (NSCLC), first-line treatment with bevacizumab combined with chemotherapy showed a high objective response rate of 68.8%, indicating its efficacy in this population.

The treatment was generally safe, with only 8 cases of severe adverse events related to bevacizumab and a low incidence of grade 3 adverse events (<9%), confirming that the safety profile aligns with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of first-line bevacizumab combination therapy in Chinese population with advanced non-squamous NSCLC: data of subgroup analyses from MO19390 (SAiL) study. Zhou, CC., Bai, CX., Guan, ZZ., et al.[2022]

In a study of 33 untreated acute myeloid leukemia (AML) patients receiving off-label venetoclax/azacitidine, the complete remission rate was 63.3%, which is lower than the 84.9% rate observed in a clinical trial cohort, although the difference was not statistically significant (P = .081).

The median overall survival for off-trial patients was 381 days, significantly shorter than the 880 days for trial patients (P = .041), indicating that while off-trial use is feasible, it may lead to inferior outcomes compared to clinical trial settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of venetoclax with azacitidine for untreated patients with acute myeloid leukemia. Winters, AC., Gutman, JA., Purev, E., et al.[2020]

In a study of 409 patients with metastatic colorectal cancer, first-line treatment with XELOX plus bevacizumab (XELOX-Bev) resulted in a median overall survival of 25 months, compared to 20 months for FOLFIRI plus bevacizumab (FOLFIRI-Bev), indicating XELOX-Bev is more effective.

XELOX-Bev also demonstrated a higher response rate of 56.4% compared to 26.1% for FOLFIRI-Bev, along with a better safety profile, making it a preferable first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

XELOX plus bevacizumab vs. FOLFIRI plus bevacizumab treatment for first-line chemotherapy in metastatic colon cancer: a retrospective study of the Anatolian Society of Medical Oncology. Duran, AO., Karaca, H., Besiroglu, M., et al.[2020]

In a phase 2 clinical trial involving 133 patients with refractory metastatic colorectal cancer, the addition of atezolizumab to capecitabine and bevacizumab therapy resulted in a median progression-free survival (PFS) of 4.4 months compared to 3.6 months for the placebo group, indicating a potential benefit, although not clinically meaningful.

Patients with microsatellite-stable disease and those without liver metastasis showed greater benefits from the combination therapy, suggesting that specific patient characteristics may influence the efficacy of atezolizumab in this treatment context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Capecitabine and Bevacizumab With or Without Atezolizumab for the Treatment of Refractory Metastatic Colorectal Cancer: A Randomized Clinical Trial. Mettu, NB., Ou, FS., Zemla, TJ., et al.[2022]

In a study of nine AML patients with acquired resistance to venetoclax, the typical BCL2 mutation associated with resistance was not found, suggesting that this mutation is not necessary for developing resistance in AML.

The study identified that existing mutations, particularly the expansion of FLT3-ITD, were primarily responsible for venetoclax resistance, indicating that monitoring these mutations could help in developing strategies to prevent or overcome resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Not BCL2 mutation but dominant mutation conversation contributed to acquired venetoclax resistance in acute myeloid leukemia. Zhang, X., Qian, J., Wang, H., et al.[2022]

In a Japanese subgroup of the phase 3 VIALE-A trial, venetoclax-azacitidine significantly improved overall survival rates compared to placebo-azacitidine, with 67% of patients alive at 12 months versus 46% in the placebo group.

The treatment also resulted in a high complete response (CR) and CR with incomplete hematologic recovery (CRi) rate of 67%, while maintaining a safety profile similar to the global study, indicating it is a viable first-line treatment for Japanese patients with acute myeloid leukemia ineligible for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. Yamamoto, K., Shinagawa, A., DiNardo, CD., et al.[2023]

The combination of 225 Ac-lintuzumab and venetoclax showed a synergistic effect in killing tumor cells in venetoclax-resistant acute myeloid leukemia (AML) models, indicating a potential new treatment strategy.

This combination therapy not only induced DNA damage but also reduced MCL-1 protein levels, which is linked to resistance against venetoclax, leading to better tumor control and prolonged survival in preclinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

225Ac-labeled CD33-targeting antibody reverses resistance to Bcl-2 inhibitor venetoclax in acute myeloid leukemia models. Garg, R., Allen, KJH., Dawicki, W., et al.[2021]

Citations

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Clinical Utility of Azacitidine in the Management of Acute ... The data suggest that oral AZA maintenance is an effective maintenance strategy to prolong survival in high-risk as well as favorable-risk AML ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2213048916300486

Clinical outcomes of AML patients treated with Azacitidine ... The AZA-001 phase III trial has demonstrated effectiveness of azacitidine (AZA) in a dose of 75 mg/m2 daily for 7 consecutive days in patients with high-risk ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2425/531542/Real-World-Treatment-Patterns-and-Outcomes-with

Real-World Treatment Patterns and Outcomes with Oral ... At 12 mo, estimated OS and rwRFS rates from Oral-AZA initiation were 88.2% (standard error [SE], 2.3) and 85.5% (SE, 2.5), respectively. Median ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2817034/

5-azacitidine prolongs overall survival in patients with ... Patients with intermediate-2 and high-risk myelodysplastic syndrome (MDS) have a survival rate of 0.4 to 1.2 years as well as a high risk of their disease ...

5. nature.com nature.com/articles/s41375-025-02730-3

Outcomes of patients treated with venetoclax plus ... The 5-year relative survival of patients with AML is ~32%, and survival rates are dependent on age at diagnosis. Patients <50 years of age have ...

6. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/2915/503393/Encouraging-Efficacy-Observed-in-Bexmab-Study-A

Encouraging Efficacy Observed in Bexmab Study: A Phase 1/2 ... The ongoing BEXMAB clinical study investigates safety and efficacy of BEX combined with standard of care (SoC) in patients with myeloid malignancies.

7. faron.com faron.com/releases-and-publications/farons-bexmarilimab-demonstrates-immune-activating-and-drug-sensitizing-potential-in-myeloid-malignancies/

Faron's Bexmarilimab demonstrates immune-activating and ... New preclinical data published in Scientific Reports confirms CLEVER-1 inhibition by Bexmarilimab increases antigen presentation and overcoming resistance to ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05428969

NCT05428969 | A Study to Assess Safety, Tolerability and ... This is a study to assess the safety of increasing dose levels of bexmarilimab when combined with standard of care (SoC) in patients with myelodysplastic ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40449509/

Bexmarilimab plus azacitidine for high-risk myelodysplastic ... Bexmarilimab in combination with azacitidine has a manageable safety profile, consistent with azacitidine, and shows promising clinical activity in patients ...

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123095174

Encouraging Efficacy Observed in Bexmab Study: A Phase ... A Phase 1/2 study to assess safety and efficacy of bexmarilimab in combination with standard of care in myeloid malignancies.