Vibecotamab for Acute Myeloid Leukemia

Overseen By Nicholas Short, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antileukemic agents

Disqualifiers: Organ dysfunction, Serious infection, HIV, 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: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called vibecotamab (also known as XmAb14045) to determine its safety and effectiveness for people with certain blood cancers. It focuses on two groups: those with acute myeloid leukemia (AML) who still show signs of the disease after treatment, and those with myelodysplastic syndrome (MDS) that did not improve with standard therapy. Eligible participants include individuals with AML who have undergone prior chemotherapy and those with MDS whose condition did not improve with other drugs. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people.

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.

Is there any evidence suggesting that vibecotamab is likely to be safe for humans?

Research has shown that vibecotamab is generally safe for people with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). It has been tested in patients whose AML and MDS have returned or are difficult to treat. Results indicate that patients tolerate the treatment well. The main side effect reported was cytokine release syndrome (CRS), a strong immune system reaction, which was usually mild to moderate.

For patients with MDS, one study found that 68% responded well after other treatments failed. This suggests that vibecotamab may be effective for those who have not had success with other therapies. Overall, studies show that vibecotamab is a promising treatment with manageable side effects for AML and MDS patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute myeloid leukemia?

Vibecotamab is unique because it targets CD123, a protein often found on the surface of leukemia cells, which is different from standard treatments like chemotherapy that broadly attack rapidly dividing cells. This targeted approach allows for a more precise attack on cancer cells, potentially reducing damage to normal cells and minimizing side effects. Researchers are excited about Vibecotamab because it uses a bispecific antibody design, which can engage both the cancer cells and the body's immune system to work together in fighting the leukemia. This dual action could offer a more effective treatment option for patients with acute myeloid leukemia, especially those who have residual disease after initial therapies.

What evidence suggests that vibecotamab might be an effective treatment for acute myeloid leukemia?

Research has shown that vibecotamab holds promise for treating acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). This trial will divide participants into two cohorts: one for AML and another for MDS post-HMA failure. Studies have found that vibecotamab, a type of antibody therapy, effectively helped patients with relapsed or hard-to-treat AML achieve complete responses. In MDS patients who did not respond to previous treatments, the treatment achieved a response rate of up to 68%. Vibecotamab targets specific proteins on cancer cells, aiding the immune system in finding and attacking these cells. Overall, the treatment has shown a good safety profile and has been well-tolerated in these patient groups. ^{2 4 5 6 7}

Who Is on the Research Team?

Nicholas Short

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Vibecotamab

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

The study evaluated MK-8242 in 26 subjects with refractory/recurrent acute myeloid leukemia (AML), finding that a 7on/14off dosing regimen (210mg or 300mg BID) had a more favorable safety profile compared to the 7on/7off regimen, with no dose-limiting toxicities observed in the higher doses.

Efficacy was demonstrated with responses including one partial response and one complete response in patients, suggesting that MK-8242, an HDM2 inhibitor, warrants further investigation for treating AML.

NCBI (Pubmed)

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). Ravandi, F., Gojo, I., Patnaik, MM., et al.[2018]

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]

Citations

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Updated Results from a Phase II Study of Vibecotamab, a CD3 ... Vibecotamab was safe and active in low-blast, high-risk myeloid ... Complete Responses in Relapsed/Refractory Acute Myeloid Leukemia (AML) ...

2. investors.xencor.com investors.xencor.com/news-releases/news-release-details/xencor-present-data-phase-1-study-vibecotamab-acute-myeloid

Xencor to Present Data from Phase 1 Study of Vibecotamab in ... Data from the Phase 1 study of vibecotamab suggest that patients with AML having low baseline disease burden and specific T-cell signatures may be more likely ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10632668/

Phase 1 study of vibecotamab identifies an optimized dose for ... A dose-optimized schedule of priming, step-up, and target vibecotamab doses mitigated CRS while achieving response. Low blast-count AML and low PD-1 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02730312

NCT02730312 | PH 1 Study to Evaluate Safety and ... Phase 1 study of vibecotamab identifies an optimized dose for treatment of relapsed/refractory acute myeloid leukemia. Blood Adv. 2023 Nov 14;7(21):6492 ...

5. cancernetwork.com cancernetwork.com/view/phase-1-study-of-vibecotamab-identifies-an-optimized-dose-for-treatment-of-relapsed-refractory-acute-myeloid-leukemia

Phase 1 Study of Vibecotamab Identifies an Optimized ... A phase 1 clinical trial has found the optimal dosing schedule with a tolerable safety profile of vibecotamab in patients with relapsed/ ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37647601/

Phase 1 study of vibecotamab identifies an optimized dose ... This phase 1 study's primary objectives were safety and tolerability and identification of a maximum tolerated dose/recommended dose for use as monotherapy in ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118696636

613.Acute Myeloid Leukemia: Clinical Studies Complete ... Vibecotamab demonstrated evidence of antileukemic activity in heavily pretreated patients with relapsed/refractory AML treated at the ≥0.75 μg/kg doses cohorts ...