MBG453 for Preleukemia

Recruiting at 2 trial locations

Overseen By Andrew Brunner, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: TIM-3 inhibitors, Prednisone

Disqualifiers: Chemotherapy, Radiotherapy, Autoimmune, Transplant, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Variable (based on individual response)

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but there is a requirement to stop any investigational agents and certain treatments at least 14 days before starting the study. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug MBG453 (Sabatolimab) for preleukemia?

Research shows that Sabatolimab, when combined with other treatments, has shown promise in improving survival and providing durable clinical responses in patients with high-risk myelodysplastic syndromes and chronic myelomonocytic leukemia, which are related conditions to preleukemia. ^{1 2 3 4 5}

What is known about the safety of MBG453 (Sabatolimab) in humans?

Sabatolimab (MBG453) has been studied in combination with other treatments for conditions like myelodysplastic syndromes and chronic myelomonocytic leukemia, showing a safety profile similar to existing treatments. In trials, it was generally well-tolerated, suggesting it is safe for human use in these contexts. ^{2 3 4 6 7}

How is the drug MBG453 unique for treating preleukemia?

MBG453, also known as sabatolimab, is unique because it targets TIM-3, a protein on immune and cancer cells, to both reactivate the immune system and directly attack cancer cells, offering a novel approach compared to traditional treatments. ^{3 4 6 7 8}

What is the purpose of this trial?

This research study is assessing the efficacy of MBG-453, a humanized monoclonal antibody, in treating myelodysplastic syndromes (MDS). The name of the study drug involved in this study is MBG453.

Research Team

Andrew M Brunner, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for adults with lower risk Myelodysplastic Syndromes (MDS) who need regular red blood cell transfusions, have not responded to previous treatments, or can't tolerate other medications. It's also open to those with specific genetic changes in their MDS and no available standard treatment options.

Inclusion Criteria

Patients with platelets < 50k/uL or ANC < 500 cells/uL who are felt to require treatment per the treating physician

I have MDS with '5q- syndrome' and lenalidomide didn't work for me.

I can't have standard treatments but have had luspatercept before.

Exclusion Criteria

I have another type of cancer that hasn't been treated yet.

Participants with clinically active HBV or HCV

I have not received a live vaccine in the last 28 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MBG453 on Day 1 of each 28-day cycle for as long as they and their doctor believe they are benefiting

Variable (based on individual response)

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• MBG453

Trial Overview The study is testing MBG453, a humanized monoclonal antibody designed to treat MDS. Researchers want to see how effective it is at improving the condition of patients who haven't had success with other therapies.

Participant Groups

Group I: MG MBG453 Experimental Treatment 1 Intervention

Participants will be given MBG453 On Day 1 of each cycle 28 days (4 weeks) study cycle

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Findings from Research

TIM-3 is a key immune checkpoint protein that plays a significant role in cancer immunosuppression and is a promising target for immunotherapy, particularly in solid tumors and myeloid leukemia stem cells.

Blocking TIM-3 has been shown to directly inhibit leukemia cells while also restoring T cell activation, suggesting it could enhance the effectiveness of cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting TIM-3 for hematological malignancy: latest updates from the 2022 ASH annual meeting. Tan, J., Tan, H., Li, Y.[2023]

Sabatolimab, an immunotherapy targeting TIM-3, was found to have a safety profile similar to hypomethylating agents (HMAs) when used in combination for treating high- or very high-risk myelodysplastic syndromes (HR/vHR-MDS) and chronic myelomonocytic leukemia (CMML).

The combination of sabatolimab and HMAs demonstrated durable clinical responses in patients, indicating its potential effectiveness and supporting further research into its use in MDS, CMML, and acute myeloid leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib study of sabatolimab (MBG453), a novel immunotherapy targeting TIM-3 antibody, in combination with decitabine or azacitidine in high- or very high-risk myelodysplastic syndromes. Brunner, AM., Esteve, J., Porkka, K., et al.[2023]

Sabatolimab is a novel immunotherapy targeting TIM-3, designed to reactivate the immune system and directly attack TIM-3+ leukemic cells, which could improve outcomes for patients with higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML).

The phase III STIMULUS-MDS2 trial is investigating the combination of sabatolimab and azacitidine to assess its effectiveness in enhancing survival rates for patients who are unfit for hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

STIMULUS-MDS2 design and rationale: a phase III trial with the anti-TIM-3 sabatolimab (MBG453) + azacitidine in higher risk MDS and CMML-2. Zeidan, AM., Giagounidis, A., Sekeres, MA., et al.[2023]

Sabatolimab, a humanized anti-TIM-3 monoclonal antibody, is being developed for treating myeloproliferative disorders like acute myeloid leukemia, showcasing its potential as a novel immunotherapy.

This therapy works through multiple mechanisms, including blocking TIM-3 and its ligands, modulating leukemic cell self-renewal, and promoting antibody-dependent phagocytosis of TIM-3-expressing leukemic cells, which may enhance the overall antitumor immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TIM-3: a tumor-associated antigen beyond checkpoint inhibition? Barth, S., Naran, K.[2023]

In a phase 2 trial involving 127 patients with higher-risk myelodysplastic syndromes, the addition of sabatolimab to hypomethylating agents did not significantly improve complete response rates or progression-free survival compared to placebo.

Despite the lack of significant efficacy, sabatolimab was generally well-tolerated, with manageable safety profiles, although there was one treatment-related death due to pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial. Zeidan, AM., Ando, K., Rauzy, O., et al.[2023]

In a phase I/II study involving 219 patients with advanced solid tumors, the combination of sabatolimab and spartalizumab was well tolerated, with fatigue being the most common treatment-related side effect.

While no responses were observed with sabatolimab alone, the combination treatment showed preliminary antitumor activity, with 5 patients achieving partial responses in various cancers, suggesting potential efficacy in specific populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/Ib Clinical Trial of Sabatolimab, an Anti-TIM-3 Antibody, Alone and in Combination with Spartalizumab, an Anti-PD-1 Antibody, in Advanced Solid Tumors. Curigliano, G., Gelderblom, H., Mach, N., et al.[2023]

The small molecule SMI402 effectively binds to the TIM-3 immune checkpoint, preventing its interaction with other molecules that contribute to T cell dysfunction, which is crucial in the tumor microenvironment.

In mouse models of cancer, SMI402 not only inhibited tumor growth but also enhanced the infiltration and function of CD8+ T cells and natural killer (NK) cells, suggesting its potential as a promising candidate for cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of a novel small-molecule inhibitor targeting TIM-3 for cancer immunotherapy. Wu, M., Wu, A., Zhang, X., et al.[2023]

Targeting the Tim-3 inhibitory receptor on T cells may enhance anti-tumor immunity in bladder cancer, especially since many patients do not respond to existing therapies like CTLA-4 and PD-1/PD-L1 blockade.

Tim-3 expression increases with the severity of bladder cancer, suggesting that developing monoclonal antibodies against Tim-3, either alone or with other treatments, could lead to better outcomes for patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Potential of T Cell Immunoglobulin and Mucin-Domain Containing-3 (Tim-3) in Designing Novel Immunotherapy for Bladder Cancer. Mohsenzadegan, M., Bavandpour, P., Nowroozi, MR., et al.[2022]

References

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

Targeting TIM-3 for hematological malignancy: latest updates from the 2022 ASH annual meeting. [2023]

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

Phase Ib study of sabatolimab (MBG453), a novel immunotherapy targeting TIM-3 antibody, in combination with decitabine or azacitidine in high- or very high-risk myelodysplastic syndromes. [2023]

3. England pubmed.ncbi.nlm.nih.gov

STIMULUS-MDS2 design and rationale: a phase III trial with the anti-TIM-3 sabatolimab (MBG453) + azacitidine in higher risk MDS and CMML-2. [2023]

4. England pubmed.ncbi.nlm.nih.gov

TIM-3: a tumor-associated antigen beyond checkpoint inhibition? [2023]

5. England pubmed.ncbi.nlm.nih.gov

Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial. [2023]

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

Phase I/Ib Clinical Trial of Sabatolimab, an Anti-TIM-3 Antibody, Alone and in Combination with Spartalizumab, an Anti-PD-1 Antibody, in Advanced Solid Tumors. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Identification of a novel small-molecule inhibitor targeting TIM-3 for cancer immunotherapy. [2023]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

The Potential of T Cell Immunoglobulin and Mucin-Domain Containing-3 (Tim-3) in Designing Novel Immunotherapy for Bladder Cancer. [2022]