Vibecotamab for Acute Myeloid Leukemia

Recruiting in Palo Alto (17 mi)

Overseen by Nicholas Short

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antileukemic agents

Disqualifiers: Organ dysfunction, Serious infection, HIV, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing vibecotamab, a medicine that helps the immune system target cancer cells, in patients with AML or MDS who haven't responded to standard treatments. It works by connecting immune cells to cancer cells, making it easier for the immune system to attack the cancer.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking any antileukemic or chemotherapy agents at least 7 days or 5 half-lives before joining. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug Vibecotamab (XmAb14045) for treating Acute Myeloid Leukemia?

Recent advances in targeted and antibody-based therapies for acute myeloid leukemia (AML) have shown better response rates and less toxicity compared to standard treatments. Immunotherapies, like antibody-based treatments, have been promising in other blood cancers, suggesting potential effectiveness for AML. ^{1 2 3 4 5}

What makes the drug Vibecotamab unique for treating acute myeloid leukemia?

Vibecotamab is a bispecific T-cell engager antibody that uniquely targets both CD3 on T-cells and CD123 on leukemia cells, helping the immune system directly attack the cancer cells, which is different from traditional chemotherapy or single-target antibodies. ^{2 6 7 8 9}

Research Team

Nicholas Short

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults over 18 with Acute Myeloid Leukemia (AML) in remission but still showing signs of disease, or Myelodysplastic Syndrome (MDS) unresponsive to prior treatments. Participants must have a certain level of CD123 expression on cancer cells and be able to perform daily activities with some limitations. Women who can bear children and men must use effective birth control.

Inclusion Criteria

Signed informed consent

My AML shows signs of returning or not going away, with a specific test result.

My MDS blasts are at least 20% positive for CD123.

Exclusion Criteria

Patients with a prior or concurrent malignancy whose natural history or treatment is not anticipated to interfere with the safety or efficacy assessment of the investigational regimen may be included only after discussion with the PI

I haven't taken any cancer medication in the last 7 days or 5 half-lives.

Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vibecotamab intravenously over 4 cycles, each cycle lasting 28 days

16 weeks

Cycle 1: 6 visits (in-person), Cycles 2-4: 4 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Vibecotamab (Monoclonal Antibodies)

Trial Overview The trial is testing vibecotamab, an antibody targeting leukemia cells, along with supportive medications like dexamethasone, acetaminophen, and diphenhydramine for safety and effectiveness in AML patients with residual disease and MDS patients after treatment failure.

Participant Groups

Group I: MDS post-HMA failure cohort only Experimental Treatment 4 Interventions

Each study cycle is 28 days. Vibecotamab by vein (IV) over about 2 hours On Days 1, 3, 5, 8, 15 and 22 of Cycle 1 and then on Days 1, 8, 15 and 22 of Cycles 2-4.

Group II: AML MRD cohort only Experimental Treatment 4 Interventions

Each study cycle is 28 days. Vibecotamab by vein (IV) over about 2 hours On Days 1, 3, 5, 8, 15 and 22 of Cycle 1 and then on Days 1, 8, 15 and 22 of Cycles 2-4.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Dr. Peter WT Pisters

M.D. Anderson Cancer Center

Chief Executive Officer since 2017

MD from University of Western Ontario

Dr. Jeffrey E. Lee

M.D. Anderson Cancer Center

Chief Medical Officer

MD from Stanford University School of Medicine

Findings from Research

Targeted and antibody-based therapies for acute myeloid leukemia (AML) show higher response rates and lower toxicity compared to standard treatments, marking a significant advancement in AML therapy.

The review emphasizes the need for improved frontline therapies for elderly patients and highlights the potential of molecularly targeted therapies for all AML patients, both in initial treatment and in cases where the disease has relapsed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myeloid leukemia: advancing clinical trials and promising therapeutics. Daver, N., Cortes, J., Kantarjian, H., et al.[2018]

Recent advancements in the treatment of acute myeloid leukemia (AML) include new drugs and improved therapies, but long-term survival rates for certain types of AML remain low, highlighting the need for better treatments.

Immunotherapies, such as antibody-based therapies and checkpoint inhibitors, show promise for AML but face challenges due to the unique characteristics of AML cells, necessitating further research into effective antigenic targets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in Acute Myeloid Leukemia: A Literature Review of Emerging Strategies. Guarnera, L., Bravo-Perez, C., Visconte, V.[2023]

The combination of ficlatuzumab, an anti-HGF antibody, with cytarabine showed a favorable safety profile in a phase Ib trial with 17 patients, establishing 20 mg/kg as the recommended dose and achieving a 53% overall response rate with all complete remissions.

The treatment effectively suppressed the p-MET pathway, and high-dimensional analyses revealed that interferon response genes could predict adverse outcomes, highlighting the potential for personalized treatment strategies in acute myeloid leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of MET Signaling with Ficlatuzumab in Combination with Chemotherapy in Refractory AML: Clinical Outcomes and High-Dimensional Analysis. Wang, VE., Blaser, BW., Patel, RK., et al.[2022]

Recent advances in molecular diagnostics for acute myeloid leukemia (AML) have improved our understanding of the disease, particularly through the identification of key mutations like FLT3, which can guide treatment decisions and risk stratification for patients, especially regarding allogeneic transplantation.

New therapeutic targets have been identified, including FLT3 mutations for tyrosine kinase inhibitors and CD33 for monoclonal antibodies, paving the way for personalized medicine approaches that aim to provide effective treatments with reduced toxicity for AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapy of acute myeloid leukemia in 2012: towards individualized therapy. Foran, JM.[2015]

Immune checkpoint inhibitors alone have shown limited effectiveness in treating acute myeloid leukemia (AML), indicating that monotherapy may not be sufficient for this type of cancer.

Combining immune checkpoint inhibitors with hypomethylating agents appears to be a safe and potentially more effective approach, with ongoing clinical trials exploring these combinations to enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors in Acute Myeloid Leukemia: Novel Combinations and Therapeutic Targets. Stahl, M., Goldberg, AD.[2020]

Magrolimab, an antibody that targets CD47, shows clinical activity in treating acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) by promoting macrophage phagocytosis of cancer cells.

Sabatolimab, which inhibits the TIM3 protein, enhances T-cell function and induces tumor cell death, demonstrating promising results in AML/MDS treatment, highlighting the potential of immunotherapy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes. Gallazzi, M., Ucciero, MAM., Faraci, DG., et al.[2022]

The study identifies LILRB4 as a promising target for antibody-drug conjugates (ADCs) in treating acute myelomonocytic (M4) and acute monocytic (M5) leukemia, as it is expressed at higher levels on these cancer cells compared to normal cells.

The developed anti-LILRB4 ADCs demonstrated high potency in killing LILRB4-positive AML cells while sparing normal progenitor cells, showing significant therapeutic effects and low toxicity in a mouse model of human AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LILRB4-targeting Antibody-Drug Conjugates for the Treatment of Acute Myeloid Leukemia. Anami, Y., Deng, M., Gui, X., et al.[2022]

Immune-based therapies, including monoclonal antibodies and CAR-T cells, are being explored for treating acute myeloid leukemia (AML), which is challenging due to its poor prognosis, especially in older patients or those with relapsed disease.

Current research focuses on various strategies, such as bispecific T-cell engagers and immune checkpoint inhibitors, to enhance the immune response against leukemia cells, with ongoing clinical trials expected to clarify their effectiveness and safety in AML treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Harnessing the Immune System Against Leukemia: Monoclonal Antibodies and Checkpoint Strategies for AML. Masarova, L., Kantarjian, H., Garcia-Mannero, G., et al.[2023]

References

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

Acute myeloid leukemia: advancing clinical trials and promising therapeutics. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Immunotherapy in Acute Myeloid Leukemia: A Literature Review of Emerging Strategies. [2023]

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

Inhibition of MET Signaling with Ficlatuzumab in Combination with Chemotherapy in Refractory AML: Clinical Outcomes and High-Dimensional Analysis. [2022]

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

Targeted therapy of acute myeloid leukemia in 2012: towards individualized therapy. [2015]

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

A phase I trial of the human double minute 2 inhibitor (MK-8242) in patients with refractory/recurrent acute myelogenous leukemia (AML). [2018]

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

Immune Checkpoint Inhibitors in Acute Myeloid Leukemia: Novel Combinations and Therapeutic Targets. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes. [2022]

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

LILRB4-targeting Antibody-Drug Conjugates for the Treatment of Acute Myeloid Leukemia. [2022]

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

Harnessing the Immune System Against Leukemia: Monoclonal Antibodies and Checkpoint Strategies for AML. [2023]