Clinical trial NCT06679582: Luveltamab Tazevibulin (STRO-002) in Infants and Children < 12 Years of Age with Relapsed/Refractory CBFA2T3::GLIS2 AML
Official title: A Phase 1/2, Open-label Study Evaluating the Efficacy, Safety, and Pharmacokinetics (PK) of Luveltamab Tazevibulin (STRO-002) in Infants and Children < 12 Years of Age with CBFA2T3::GLIS2 Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia (AML)
Keywords: CBFA2T3::GLIS2 Fusion
CBFA2T3::GLIS2 AML
RAM Phenotype (CD56pos); CD45, CD38, HLA-DR weak or absent)
REFRaME
AML, Child
Pediatric AML
Levelatamab
REFRaME-P1
Lead sponsor: Sutro Biopharma, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Children's Oncology Group
name: Innovative Therapies For Children with Cancer Consortium
First posted: 2024-11-07
Enrollment: 24
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This trial has two parts, Part 1 will use a parallel model by assessing two luveltamab tazevibulin doses (3.5 and 4.3 mg/kg every 2 weeks). Two cohorts will be run in parallel. The transition from part 1 to part 2 is sequential, with part 2 testing the dose selected at the end of part 1.
Primary purpose: TREATMENT

Brief summary: This trial will evaluate whether luveltamab tazevibulin is well tolerated and active against a rare form of AML carrying a particular genetic abnormality called CBFA2T3::GLIS2 that arises in infants and children. To be treated in this trial children must have a leukemia which did not respond or recurred after prior treatment. Luveltamab tazevibulin is an antibody-drug conjugate, which brings tazevibulin, an anticancer drug, to a molecule called FOLR1, present on the surface of CBFA2T3::GLIS2 AML cells.

Detailed description: This is a registrational international, multicenter, two-part open label Phase 1/2 trial in an extremely rare pediatric disease (around 17 new patients a year in US and 10 in EU). Part 1 randomizes subjects 1:1 to one of two luveltamab tazevibulin dose cohorts (1a and 1b). Part 2 further evaluates the safety and the efficacy of the selected dose. Subjects who achieve complete remission after two cycles of treatment may continue luveltamab tazevibulin as monotherapy, while non-responders at PI discretion may add luveltamab tazevibulin with stadard of care (SOC) AML treatments. Luveltamab tazevibulin is given IV every two week as monotherapy and every 4 weeks when given with chemotherapy.

Eligibility criteria: Inclusion Criteria:

* AML with CBFA2T3::GLIS2 gene fusion centrally confirmed
* Refractory or relapsed disease with ≥ 5% bone marrow involvement with leukemic blasts by morphology
* Age \< 12 years.
* Lansky performance of ≥ 50
* Adequate organ functions

Exclusion Criteria:

* Active central nervous system (CNS) disease (CNS3)
* Pre-existing clinically significant corneal disorders or constitutional diseases associated with an increased risk of AML treatment toxicities
* Active or uncontrolled infections or other active severe intercurrent illnesses,
* Prior treatment with a FOLR1- targeting ADCs or with ADCs that contain a tubulin inhibitor
* History of allogeneic hematopoietic stem cell transplant or any organ transplant in the prior 84 days
* Graft versus host disease (GVHD) of any grade or GVHD treatment with exception of low dose steroids

Primary outcomes:
measure: Evaluate efficacy of luveltamab tazevibulin monotherapy
timeFrame: Up to 12 weeks
Secondary outcomes:
measure: Assess additional efficacy outcome measures
timeFrame: Up to 2 years
measure: Evaluate safety measures
timeFrame: Up to 2 years
measure: To characterize the PK of luveltamab tazevibulin
timeFrame: Up to 2 years
measure: Assess the immunogenic potential of luveltamab tazevibulin
timeFrame: Up to 2 years
measure: Assess additional efficacy outcome measures
timeFrame: Up to 2 years
measure: Assess additional efficacy outcome measures
timeFrame: Up to 2 years
measure: Assess additional efficacy outcome measures
timeFrame: Up to 2 years
measure: Assess additional efficacy outcome measures
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Childrens Hospital of Alabama
state: Alabama
city: Washington
country: United States
facility: Childrens National Hospital
state: District of Columbia
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia (CHOP)
state: Pennsylvania
city: Richmond
country: United States
facility: VCU Massey Cancer Center-Adult Outpatient Pavillion
state: Virginia
Study officials:
affiliation: Sutro Biopharma
name: Craig Berman, MD
role: STUDY_DIRECTOR
References: