A clinical trial to assess the safety, distribution, effects on certain immune cells and anti-leukaemia effects of LAVA-1266 in patients with acute myeloid leukaemia or certain types of myelodysplastic syndrome

ACTRN 12624001214527

Brief Summary

This study is a first in human (FIH) clinical trial evaluating a drug called LAVA-1266 in patients with myelodysplastic syndrome (MDS) and relapsed/refractory acutenew, recent, comes with an urgent or significant sense, is sudden, sharp myeloid leukaemiacancer of blood and/or blood forming tissues (R/R AML).

Intervention/Treatment

• Drug: LAVA-1266

Inclusion Criteria

Patients are eligible to be included in the study only if all of the following criteria apply:

1. Patient must be 18 years of age or above at the time of signing the informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment..
2. Patients with documented diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of AML or MDS; (defined using the most recent International Consensus Classification (ICC) guidelines).
3. AML:
   • Patients with relapsed/refractory AML (defined as relapsed disease or refractory disease as per the most recent ELN guidelines).
   • Patients may have extramedullary disease (Note: a response monitoring plan must be developed a priori for subjects with extramedullary disease).
4. MDS:
   • Patients with MDS should have morphologically confirmed diagnosis with marrow blasts > 5%.
5. Prior lines of therapy:
   • MDS: Patients with MDS must have progressed after prior therapy with at least 4 cycles of at least one prior hypomethylating agent.
   • AML: Patients must be relapsed from or refractory to one or more prior lines of therapy which can include induction chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells, stem cell transplanta procedure that involves replacing unhealthy blood-forming cells (stem cells) with healthy stem cells (including those who have received donor lymphocyte infusions), salvage chemotherapy and/or venetoclax-based regimens.
6. Patients must have CD123-positive AML or MDS as confirmed by local flow cytometry (or immunohistochemistry).
7. Patients who are not amenable to further standard treatment or for whom no standard treatments are available as per investigator judgement.
8. Males or non-pregnant, non-breastfeeding females who fulfil any of the following criteria:
   • Surgically sterile (hysterectomycomplete or partial removal of the uterus, bilateralaffecting both sides oophorectomyremoval of one (unilateral) or both (bilateral) ovaries or bilateral salpingectomyremoval of one (unilateral) or both (bilateral) fallopian tubes, vasectomy).
   • Female of childbearing potential with a negative pregnancy test prior to first dosing and compliant with a highly effective contraceptive regimen (i.e., pregnancy rate of < 1% per year: oral contraceptives, intrauterine device, intrauterine hormone-releasing systems) from signing of the informed consent form (ICF) through 90 days after the last IMP administration. Abstinence is not considered an adequate contraceptive regimen.
   • Female, postmenopausal defined as continuous amenorrhea for at least 12 consecutive months without an alternative medical cause and/or a serum follicle-stimulating hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body measurement of > 40 IU/L.
   • Male participants with female partners must be compliant with an effective contraceptive regimen (i.e., use of male condom with female partner and assuring use of an additional highly effective contraceptive method with a failure rate of < 1% per year when having sexual intercourse with a woman of childbearing potential who is not currently pregnant) from signing of the ICF through 90 days after the last IMP administration).
   • Male, refraining from donating sperm following from signing of the ICF through 90 days after the last IMP administration.
9. Predicted life-expectancy of greater than or equal to 3 months.
10. Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group performance status of 0-2.
11. Adequate Organ Function, defined as:
    • Estimated glomerular filtration rate per local laboratory greater than or equal to 60 mL/min/1.73 m-squared.
    • Total bilirubin < 1.5 times upper limit of normal (ULN), unless in patients with known Gilbert’s syndrome who must have total bilirubin less than or equal to 3 times ULN (Patient with leukaemic organ involvement as assessed by the study investigator, Serum direct bilirubin less than or equal to 5.0 x ULN), and
    • Aspartate aminotransferase and alanine aminotransferase less than or equal to 3.0 times ULN or < 5 times ULN if leukaemic liver involvement.
12. Patients should be at least 14 days or 5 half-lives (whichever is longer) from having received prior therapy and have resolved adverse reactions to prior therapy to no more than Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells 1, except for alopeciathe partial or complete absence of hair from areas of the body where it normally grows; baldness or peripheral neuropathy.
13. Capable of giving signed and dated informed consent prior to initiation of any trial-related procedure that is not considered Standard of Care which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.