Unknown Cancer NIHR-supported project Infection & Immunity

A Phase 1, First-in-Human, Dose Escalation Study of JNJ-89853413 for Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Neoplasms

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AI plain-English summary

A new antibody-based drug, JNJ-89853413, is being tested in people for the first time, aiming to force the body’s own immune T-cells to latch onto and kill cancer cells in two hard-to-treat blood cancers. This matters because patients with relapsed or refractory acute myeloid leukemia (AML) and higher-risk myelodysplastic neoplasms (MDS) have very few treatment options left. Current therapies often fail, and survival times are short. The drug works by binding two things at once: a protein called CD33 found on the surface of AML and MDS blast cells, and a specific receptor on Vγ9Vδ2 T-cells. This physical bridge is designed to make the T-cells selectively destroy the cancer cells, sparing healthy tissue. If the trial succeeds, it could establish a safe dose and show that this bispecific antibody is tolerable enough to move into larger studies. That would open a new treatment pathway for patients who currently have no effective standard of care. The research is a first-in-human dose-escalation study, so its immediate goal is safety and dosing—not efficacy—but a positive result could eventually change clinical practice for thousands of people with these aggressive blood cancers.

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Acute leukemias are characterized by uncontrolled proliferation of immature white blood cells (WBCs) in bone marrow (soft, fatty tissue inside of bone cavities), peripheral blood and/or other sites in the body. Acute myeloid leukemia (AML) & Myelodysplastic neoplasms (MDS) are cancers in which abnormal myeloid cells, called blasts, grow uncontrollably, instead of developing into cells that fight infections & help healing.JNJ-89853413 (CD33xV?2) is a bispecific antibody* that binds CD33 protein on AML & MDS blast cells & the V?2 chain on V?9V?2 T-cells. The goal of binding these two cells together is that the T-cells will selectively kill cancer cells.*Type of protein that binds to other proteins & fights off an infection.In this study, researchers want to determine the safety & tolerability of JNJ-89853413 & to identify safe doses in participants with relapsed or refractory (R/R) AML or R/R higher-risk types of MDS.Participants aged 18 years or older or those who are at least the age of majority diagnosed with R/R AML or R/R higher-risk types of MDS.Study will be conducted in 2 parts:Part 1 (Dose Escalation): In part 1, participants will get JNJ-89853413 with increasing doses. The goal of increasing dose is to study safety of each dose & to establish a safe dose for further evaluation in part 2.Part 2 (Cohort Expansion): Participants will get treatment at the recommended dose & schedule of JNJ-89853413 established from part 1.Study will consist of a screening period followed by a treatment period. During treatment period, participants will be treated with JNJ-89853413 until worsening of AML/MDS, serious side effects, or withdrawal from study. After discontinuation of treatment, participants will be followed to monitor their health.Safety assessments include blood tests, vital sign measurements, & physical exams. Blood samples will be taken at multiple timepoints to understand how the body responds to treatment.

Researchers

Emma Searle (Principal Investigator)

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89853413AML1001 - A Phase 1, First-in-Human, Dose Escalation Study of JNJ-89853413 for Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Neoplasms
A Phase 1b Study of JNJ-75276617 in Combination with AML Directed Therapies for Participants with Acute Myeloid Leukemia Harboring KMT2A or NPM1 Alterations
75276617ALE1002: A Phase 1b Study of JNJ-75276617 in Combination with AML Directed Therapies for Participants with Acute Myeloid Leukemia Harboring KMT2A or NPM1 Alterations
A First in Human Study of the Menin-KMT2A (MLL1) Inhibitor JNJ-75276617 in Participants with Acute Leukemia
CA091-P01 (CC-91633-AML-001) - A Phase 1, open-label, dose-finding study of CC-91633 (BMS-986397) in subjects with relapsed or refractory acute myeloid leukemia or relapsed or refractory higher-risk myelodysplastic syndromes.

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