Evaluation of Luveltamab Tazevibulin (STRO-002) Monotherapy in Pediatric Patients with CBFA2T3::GLIS2 Acute Myeloid Leukemia (AML)

Trial ID: 2023-506240-16-00
Protocol: REFRaME-P1
Sponsor: Sutro Biopharma Inc.

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Diseases & Conditions

Acute myeloid leukaemia

Objectives

The primary objective of this study is to evaluate the **efficacy** of luveltamab tazevibulin monotherapy in infants and children under 12 years of age diagnosed with CBFA2T3::GLIS2 **Acute Myeloid Leukemia (AML)**. This is clinically relevant as it aims to determine the therapeutic potential of luveltamab tazevibulin in a specific pediatric population affected by a rare and aggressive form of leukemia, potentially offering a new treatment option.

Secondary objectives include:

Assessing additional efficacy outcome measures to provide a comprehensive understanding of the drug's impact.
Evaluating safety measures to ensure the treatment's risk profile is acceptable for the pediatric population.
Characterizing the pharmacokinetics (PK) of luveltamab tazevibulin to understand its absorption, distribution, metabolism, and excretion in the body.
Assessing the immunogenic potential of luveltamab tazevibulin to evaluate the likelihood of immune response development against the drug.

These secondary objectives are crucial for a holistic evaluation of the drug's performance and safety in the target population.

Participants

The clinical trial involves a total of **17 participants** diagnosed with **Acute Myeloid Leukemia (AML)**, specifically those with relapsed or refractory AML with CBFA2T3::GLIS2 fusion. The study population includes both male and female subjects under the age of 12, with a Lansky performance score of 50 or higher, indicating a moderate level of general health. Participants were selected based on specific inclusion criteria, including a diagnosis of AML with a certain level of bone marrow involvement and specific genetic translocation. The trial population is considered vulnerable due to the age group involved. Lifestyle considerations such as diet and physical activity are not specified, but participants must adhere to reproductive health guidelines, including the use of contraceptives if applicable. The selection process ensures that participants meet health criteria such as liver function, kidney function, and cardiac health, as indicated by specific laboratory values and clinical assessments.

Plans and Procedures

The clinical trial is a **Phase 1/2, open-label study** designed to evaluate the efficacy, safety, and pharmacokinetics of **luveltamab tazevibulin** in infants and children under 12 years of age diagnosed with relapsed or refractory **Acute Myeloid Leukemia (AML)** with CBFA2T3::GLIS2 fusion. The trial is not categorized as low intervention and involves the administration of the investigational product, STRO-002, as a **solution for infusion** via **intravenous use**. The study is expected to commence recruitment in September 2024 and is estimated to conclude by September 2029.

The trial design includes a sequence of study visits beginning with an inclusion (screening) visit, where eligibility is confirmed based on specific criteria such as age, performance status, and laboratory parameters. Participants must have a Lansky performance score of at least 50, and specific laboratory values must be within defined limits. The screening process also involves a lumbar puncture to confirm central nervous system disease status. Following the screening, participants will undergo regular follow-up visits to monitor the treatment's efficacy and safety, assess the complete remission rate, and evaluate secondary endpoints such as duration of remission, event-free survival, and overall survival. The end-of-study visit will conclude the participant's involvement, where final assessments and data collection will occur.

Participant involvement is expected to last throughout the trial duration unless early termination is warranted. Conditions that may lead to early termination include significant adverse events, withdrawal of consent, or any situation where continued participation is deemed not in the participant's best interest by the investigator. The primary endpoint of the study is the complete remission rate, while secondary endpoints include response rates, survival metrics, and the incidence of adverse events. The study aims to provide comprehensive data on the investigational product's impact on this specific pediatric population with AML.

Treatment

The clinical trial involves the administration of **Luveltamab Tazevibulin (STRO-002)**, an investigational medication developed by Sutro Biopharma, Inc. This experimental drug is formulated as a **solution for infusion** and is administered via the **intravenous route**. The active substance, STRO-002, is a protein-based compound, specifically categorized under "Protein - Other". The pharmaceutical form of the medication is designed for direct infusion into the bloodstream, ensuring rapid systemic distribution. The study does not specify a pediatric formulation, indicating that the same formulation is used across the study population. The frequency and dosage of administration are determined by the study protocol, although specific dosing schedules are not detailed in the provided data.

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are mentioned. The focus is solely on evaluating the efficacy, safety, and pharmacokinetics of Luveltamab Tazevibulin monotherapy in infants and children under 12 years of age diagnosed with CBFA2T3::GLIS2 **Acute Myeloid Leukemia (AML)**. Participant compliance with the treatment regimen is monitored throughout the study, although specific compliance measures are not detailed in the available information. The trial is conducted as an open-label study, allowing for direct observation of the drug's effects without the use of blinding.

Efficacy

Efficacy in this clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is the **Complete Remission (CR) rate**. Secondary endpoints include the duration of CR, response rate including complete remission with partial hematologic recovery (CRh) rate [CR + CRh], event-free survival (EFS), relapse-free survival (RFS), overall survival (OS), and the incidence and severity of adverse events (AEs) and clinical laboratory abnormalities as per NCI CTCAE v5.0. Additionally, the concentration of luveltamab tazevibulin (ADC, TAb, and SC209) in the blood and the incidence of anti-drug antibodies (ADAs) will be measured.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Signed informed consent form and pediatric assent form, if applicable
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
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

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Exclusion Criteria

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.
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.
Active or uncontrolled viral, bacterial, or fungal infection. May be receiving ongoing therapy for controlled infection
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.
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.
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.
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)

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Austria	Not Recruiting	01 Sept 2024	2
Denmark	Not Recruiting	01 Sept 2024	2
France	Not Recruiting	01 Sept 2024	2
Germany	Not Recruiting	01 Sept 2024	2
Italy	Not Recruiting	01 Sept 2024	2
The Netherlands	Not Recruiting	01 Sept 2024	—
Spain	Not Recruiting	01 Sept 2024	2
Netherlands	—	—	2