MBG-453 + Azacitidine for AML

Overseen By Courtney DiNardo, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, Immunosuppressants, TIM3 inhibitors

Disqualifiers: HIV, Active infection, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining MBG-453 (an experimental treatment) and Azacitidine for individuals with acute myeloid leukemia (AML), a type of blood cancer. Researchers seek to determine if this treatment can effectively target and manage the disease. Eligible participants should have AML, have completed some initial treatments such as a stem cell transplant, and not have any active infections or other uncontrolled 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 need to stop taking your current medications, but it does mention that you cannot be on systemic chronic corticosteroid therapy or any immunosuppressive therapy within 7 days of the first dose of the study treatment. It's best to discuss your current medications with the trial team.

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

Research has shown that using MBG-453 with azacitidine is generally safe. In earlier studies, this combination did not cause any unexpected safety problems. The side effects were similar to those expected from azacitidine alone, indicating they were not worse.

Another study found no new safety issues when using MBG-453 alone or with azacitidine. Importantly, these studies reported no treatment-related deaths in patients with newly diagnosed acute myeloid leukemia (AML).

Overall, these findings suggest that MBG-453, when combined with azacitidine, is safe enough for further testing in clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of MBG-453 and Azacitidine for treating acute myeloid leukemia (AML) because it introduces a novel approach to combatting this aggressive cancer. Unlike traditional options like chemotherapy, which broadly target rapidly dividing cells, MBG-453 is a TIM-3 inhibitor that specifically targets immune checkpoint pathways, potentially enhancing the immune system's ability to fight cancer cells. This targeted mechanism not only aims to improve the effectiveness of treatment but also holds promise for reducing some of the side effects associated with conventional therapies. By combining MBG-453 with Azacitidine, which helps to modify and regulate gene expression, there is potential for a synergistic effect that could offer better outcomes for patients with AML.

What evidence suggests that MBG-453 + Azacitidine could be an effective treatment for AML?

Research has shown that MBG-453, also known as sabatolimab, may be beneficial when combined with azacitidine for treating acute myeloid leukemia (AML). In studies involving newly diagnosed AML patients, 41.2% responded to the treatment, with some achieving complete or partial remission. This combination has demonstrated lasting effects and a safety profile similar to azacitidine alone. Participants in this trial will receive the combination of MBG-453 with azacitidine, which could be effective for AML patients. ^{1 2 3 6 7}

Who Is on the Research Team?

Courtney DiNardo, MD

Principal Investigator

The University of Texas MD Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with Acute Myeloid Leukemia (AML) who are at risk of relapse. Specific eligibility criteria details were not provided, so it's important to consult the trial organizers for more information on who can participate.

Inclusion Criteria

I had a stem cell transplant, my lymphocyte count is healthy, and I don't have active GVHD.

My kidneys work well enough, with a creatinine clearance of at least 30 mL/min.

My recent tests show I'm eligible for INTERCEPT therapy.

Exclusion Criteria

Subject is HIV positive

Patients with .5% myeloblasts in bone marrow on morphologic assessment

Presence of any general exclusion criteria outlined in the AMLM26 INTERCEPT Master Protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive targeted and tailored sequential therapy based on decision-rule guided therapy

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MBG-453

Trial Overview The study tests a combination of MBG-453 and Azacitidine as a treatment strategy for AML. It aims to assess how effective this tailored therapy is in preventing early relapse and managing clonal evolution in AML patients.

How Is the Trial Designed?

Group I: Treatment with MBG453 + Azacitidine Experimental Treatment 1 Intervention

Participants will be randomized to arm

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Australasian Leukaemia and Lymphoma Group

Collaborator

Trials

17

Recruited

4,300+

Published Research Related to This Trial

Azacitidine (AZA) demonstrated efficacy in elderly patients with acute myeloid leukemia (AML), achieving an overall response rate of 36.2% and hematologic improvement in 37.7% of patients, including those previously unresponsive to treatment.

The study found that patients who experienced any hematologic improvement had a median overall survival of 14 months, compared to 10 months for those without improvement, suggesting that even modest responses to AZA can significantly impact survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Azacitidine in the Treatment of Elderly Patients with Acute Myeloid Leukemia: Results of a Retrospective Multicenter Study. Tombak, A., Uçar, MA., Akdeniz, A., et al.[2018]

In a study involving 302 acute myeloid leukemia (AML) patients, including 172 with over 30% bone marrow blasts, azacitidine demonstrated an overall response rate of 48%, indicating its potential efficacy even in a challenging patient population.

Patients who achieved any form of disease stabilization or hematologic improvement had significantly better median overall survival (OS), with those showing a combination of responses having an OS of 18.9 months compared to just 3.2 months for those without response, suggesting that disease stabilization is a meaningful endpoint for treatment continuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine in 302 patients with WHO-defined acute myeloid leukemia: results from the Austrian Azacitidine Registry of the AGMT-Study Group. Pleyer, L., Burgstaller, S., Girschikofsky, M., et al.[2021]

In a trial involving 214 older patients with untreated acute myeloid leukemia (AML), adding azacitidine to standard chemotherapy did not improve event-free survival or overall survival compared to chemotherapy alone, with median overall survival being 15 months for the azacitidine group and 21 months for the chemotherapy-only group.

While the combination treatment resulted in higher toxicity, with more adverse events reported, it did not lead to a significant difference in early death rates, indicating that azacitidine may not be beneficial for unselected older patients with AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the Study Alliance Leukemia. Müller-Tidow, C., Tschanter, P., Röllig, C., et al.[2018]

Azacitidine is an effective front-line treatment for older patients with acute myeloid leukemia (AML), showing potential to prolong overall survival with less toxicity compared to other approved therapies.

It is particularly beneficial for older patients with unfavorable cytogenetics, and real-world clinical outcomes align closely with those observed in controlled trials, indicating its effectiveness in community settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine in adult patients with acute myeloid leukemia. Schuh, AC., Döhner, H., Pleyer, L., et al.[2018]

In a study of 38 acute myeloid leukemia (AML) patients treated with azacitidine, the median overall survival was approximately 10 months for both newly diagnosed and relapsed patients, indicating its efficacy as a treatment option for those unfit for intensive chemotherapy.

The treatment showed a 29% positive effect on reducing transfusion dependency, which was linked to better survival outcomes, highlighting the potential benefits of azacitidine in managing symptoms and improving quality of life for AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Azacitidine in De Novo and Relapsed Acute Myeloid Leukemia: A Retrospective Comparative Study. Gemuenden, C., Benz, R., Senn, O., et al.[2015]

In a phase 3 trial involving 488 patients aged 65 and older with newly diagnosed acute myeloid leukemia (AML), azacitidine significantly improved median overall survival to 10.4 months compared to 6.5 months with conventional care regimens (CCRs).

The one-year survival rate was also higher for azacitidine at 46.5% versus 34.2% for CCR, indicating that azacitidine is a promising treatment option for older patients with AML, while maintaining a safety profile consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Dombret, H., Seymour, JF., Butrym, A., et al.[2022]

In a trial involving 70 patients with relapsed/refractory acute myeloid leukemia (AML), the combination of azacitidine and nivolumab resulted in an overall response rate of 33%, with particularly promising results in patients who had not previously received hypomethylating agents, achieving a response rate of 58%.

The treatment was generally safe, with only 11% of patients experiencing grade 3 to 4 immune-related adverse events, and pretherapy levels of CD3 and CD8 in bone marrow and blood were identified as potential biomarkers for predicting patient response to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Biomarkers of Response to Azacitidine and Nivolumab in Relapsed/Refractory Acute Myeloid Leukemia: A Nonrandomized, Open-Label, Phase II Study. Daver, N., Garcia-Manero, G., Basu, S., et al.[2020]

In a study of 1406 patients receiving azacitidine, the most common severe adverse events were hematologic, with grade 3-4 anemia occurring in 43.4% of patients, which was higher than reported in clinical trials.

Despite the high frequency of adverse events, treatment discontinuation due to these events was low (5.1%), indicating that with proper management, azacitidine can be safely administered to most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events in 1406 Patients Receiving 13,780 Cycles of Azacitidine within the Austrian Registry of Hypomethylating Agents-A Prospective Cohort Study of the AGMT Study-Group. Leisch, M., Pfeilstöcker, M., Stauder, R., et al.[2022]

Azacitidine is effective for treating adult patients with acute myeloid leukemia (AML) who have 20%-30% blasts and multilineage dysplasia, significantly prolonging median overall survival compared to conventional care, as shown in the AZA-001 phase III trial.

The review also highlights the potential benefits of combining azacitidine with other treatments for AML, suggesting it may enhance patient outcomes further.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azacitidine for the treatment of patients with acute myeloid leukemia with 20%-30% blasts and multilineage dysplasia. Font, P.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04150029

NCT04150029 | A Study of MBG453 in Combination With ... This trial will seek to extend the preliminary findings of efficacy of MBG453 in combination with hypomethylating agents (HMA)

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37994196/

Phase Ib study of sabatolimab (MBG453), a novel ... Sabatolimab + HMA had a safety profile similar to that reported for HMA alone and demonstrated durable clinical responses in patients with HR/vHR-MDS. These ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118698532

Efficacy and Safety of Sabatolimab (MBG453) in ... No other treatment-related deaths were reported. Among 34 evaluable pts with ND AML, overall response rate (ORR) was 41.2%: 8 CR, 3 CRi, 3 PR.

4. ash.confex.com ash.confex.com/ash/2020/webprogram/Paper136855.html

Efficacy and Safety of Sabatolimab (MBG453 ... Among 34 evaluable pts with ND AML, overall response rate (ORR) was 41.2%: 8 CR, 3 CRi, 3 PR. M ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/ajh.27161

American Journal of Hematology | Blood Research Journal Phase Ib study of sabatolimab (MBG453), a novel immunotherapy targeting TIM-3 antibody, in combination with decitabine or azacitidine in high- or very high- ...

6. novctrd.com novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=2540

A clinical trial to learn more about the effects of MBG453 in ... The researchers did not find any new safety concerns with the use of MBG453 alone or in combination with azacitidine in this trial. However, they could only.

7. novartis.com novartis.com/news/novartis-receives-fda-fast-track-designation-sabatolimab-mbg453-myelodysplastic-syndromes

Novartis receives FDA fast track designation for ... “Study of Efficacy and Safety of MBG453 in Combination With Azacitidine in Subjects With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) ...