A study to see how safe and effective the drug Luveltamab Tazevibulin (STRO-002) is in treating infants and children under 12 years old with a specific type of acute myeloid leukemia (AML)

Prior treatment

• Radiation therapy, including CNS, < 21 days prior to the start of luveltamab tazevibulin, with the exception of no time restriction if the volume of bone marrow treated is less than 10% and also the subject has measurable/evaluable disease outside the radiation field.
• Prior treatment with folate receptor-targeting anti-cancer agent(s) or with ADCs that contain a tubulin inhibitor.
• Prior treatment with an investigational anti cancer treatment within 4 weeks or 5 half lives of the drug, whichever is shorter, prior to the first luveltamab tazevibulin infusion. a) Note: ADC therapies washout period is ≥ 3 half-lives (see Exclusion #9)
• Active or uncontrolled viral, bacterial, or fungal infection. May be receiving ongoing therapy for controlled infection
• Prior systemic chemotherapy within 21 days prior to the first luveltamab tazevibulin infusion, with the exception of: a) Hydroxyurea ≥ 1 day. b) Azacytidine/decitabine and/or venetoclax: ≥ 7 days. c) Antibody drug conjugate therapies: ≥ 3 half-lives.

Other illness

• Active CNS disease at the time of enrollment (defined as CNS3)
• Subjects with the following constitutional conditions are not eligible: Fanconi anemia, Shwachman Diamond syndrome, subjects with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21, telomere disorders, germline predispositions known, or suspected by the treating physician to increase risk of toxicity with AML therapy.
• Known human immunodeficiency virus, hepatitis B virus, or hepatitis C virus infection, unless on treatment and have an undetectable viral load.
• Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, congestive heart failure, cardiac arrhythmia, or social situations that would limit compliance with study requirements or in the opinion of the Investigator would pose an unacceptable risk to the subject. If the subject is in remission from a prior second malignancy, they may be considered for enrollment.
• History of severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biologic composition to any agents used in study or in the manufacturing of the cells.

Lab values

• Subjects with a history of an allogeneic (non-autologous) hematopoietic stem cell transplant, boost infusion (any stem cell product; not including donor lymphocyte infusion [DLI]), or any organ transplant are excluded if any of the following are met: a) Subjects are less than 84 days post-transplant. b) Subjects have graft-versus-host disease (GVHD) of any severity and/or receive any immunosuppressive therapy with the exception of topical steroids for cutaneous GVHD and/or systemic steroid in doses equal or less than 10 mg of prednisone daily, which are permitted if doses were not changed in the last 14 days. Prednisone dose must be adjusted for body surface area in young children. Physiologic doses of hydrocortisone for subjects with adrenal insufficiency are allowed. c) Subjects who after relapse continue to receive cyclosporine, tacrolimus, or other agents to treat or prevent either GVHD post-bone marrow transplant or organ rejection post-transplant are not eligible. They must be off medications to treat or prevent either GVHD post-bone marrow transplant or organ rejection post transplant for at least 28 days prior to enrollment. A stable steroid dose as mentioned above is allowed. d) Cellular therapy: less than 30 days after the completion of DLI or any type of cellular therapy (eg, modified T cells, NK cells, dendritic cells, etc.) at enrollment. After 30 days, subjects will be eligible.

Age

• Clinically significant active or chronic corneal disorder, particularly corneal epitheliopathy, or any eye disorder that may predispose subject to this condition, or unable to comply with an age-appropriate ophthalmic examination.

• Signed informed consent form and pediatric assent form, if applicable
• Female subjects that have experienced menarche and male subjects that have reached puberty must agree to undergo physician-approved reproductive education and discuss the side effects of the study therapy on reproduction with parent(s) and/or guardian(s).
• Female subjects who have experienced menarche must have a negative pregnancy test within 7 days of the first dose of study drug. All subjects (male and female) who have undergone puberty and are potentially sexually active must agree to use a physical barrier (condoms) during heterosexual contact. At the discretion of the treating physician females may also use additional contraceptive methods, including hormonal contraceptives. Pregnancy prevention must continue while participating in the study, during dose interruptions, and for at least 6 months following luveltamab tazevibulin discontinuation
• Diagnosis of relapsed or refractory AML with CBFA2T3::GLIS2 fusion. Subjects must have refractory (induction/reinduction failure) or relapsed disease with ≥ 5% bone marrow involvement with leukemic blasts as determined by morphology (by local laboratory testing). Subjects must undergo a lumbar puncture at screening to confirm (CNS) disease. Subjects with CNS1 and CNS2 are eligible (please refer to definitions below in Inclusion Criteria #3). Flow cytometry results (by central or local laboratory) will not affect subject eligibility. Eligibility requires the documentation of the CBFA2T3::GLIS2 translocation.
• Age < 12 years
• Lansky performance of ≥ 50
• Direct bilirubin < 1.5 × upper limit of normal (ULN). Subjects with Gilbert’s disease will also require direct bilirubin < 1.5 × ULN.
• Alanine aminotransaminase (ALT) and aspartate aminotransferase (AST) < 2.5 × ULN (unless related to leukemic involvement). • Subjects with hepatic EMD, ALT and AST may be ≤ 5.0 × ULN. • To note, for subjects with hepatic EMD who have baseline LFT > 2.5 × ULN but < 3 × ULN, DLT criteria for LFT remain. For those who start with LFT > 3 × ULN, they will not be evaluable for LFT DLT
• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70/mL/min/1.73 m2 OR a serum creatinine based on age/gender
• Corrected QTcF < 450 msecs
• Left ventricular ejection fraction > 50% by ECHO