Cusatuzumab in Combination With Background Therapy for the Treatment of Participants With Acute Myeloid Leukemia

Conditions

Leukemia, Myeloid, Acute

Brief summary

The purpose of the study is to characterize safety and tolerability of cusatuzumab in combination with various therapies used to treat acute myeloid leukemia (AML).

Roboz GJ, Pabst T, Aribi A, Brandwein JM, Döhner H, Fiedler W, Riether C, Gandini D, Geddes M, Hou JZ, Yee K, Hultberg A, Huselton E, Jacobs J, Zabrocki P, Lech-Marańda E, Louwers M, Nottage K, Platzbecker U, Rampal R, Salman M, Shah P, Wilson K, Stuart M, Subklewe M, Sumbul A, Wang ES, Wierzbowska A, Yao B, Patel R, George A, Islam N, Smith C, Boyiadzis M, Borthakur G.

2026-09-03

10.3324/haematol.2026.300917

Trial in Progress: A Multicenter, Open Label, Randomized, Phase 2 Study of Venetoclax and Azacitidine Plus Cusatuzumab Versus Venetoclax and Azacitidine Alone in Newly Diagnosed AML Patients Who Are Not Candidates for Intensive Therapy

Gail J. Roboz, Ahmed Aribi, Adrian F. Ochsenbein, Carsten Riether, Monic J. Stuart et al. (11 authors)

Blood2024-11-05

10.1182/blood-2024-202648

Cusatuzumab plus azacitidine in newly diagnosed acute myeloid leukaemia ineligible for intensive chemotherapy (CULMINATE): part one of a randomised, phase 2, dose optimisation study.

Pabst T, Papayannidis C, Demirkan F, Doronin V, Fogliatto LM, Guttke C, Gyan E, Hamad N, Herrera P, Hultberg A, Jacobs J, Johnson AJ, Langlois A, Ma X, Martinelli G, Arnan M, Müller R, Nottage K, Ofran Y, Özcan M, Samoilova O, Tolbert JA, Trudel GC, Xiu L, Vey N, Wei AH.

2023-11-0110 citations

10.1016/s2352-3026(23)00207-7

Interventions

DRUGAzacitidine

Azacitidine will be administered 75 mg/m\^2 subcutaneously or intravenously.

DRUGVenetoclax

Venetoclax will be administered orally and the dose will ramp-up to 400 mg.

DRUGCusatuzumab

Cusatuzumab will be administered as a dose of 10mg/kg or 20mg/kg intravenously.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Diagnosis of acute myeloid leukemia (AML) according to World Health Organization 2016 criteria . Participants with acute promyelocytic leukemia (APL) are not eligible * Must be ineligible for intensive chemotherapy * De novo or secondary AML * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Previously untreated AML except: emergency leukapheresis, hydroxyurea, and/or 1 dose 1-2 gram per meter square (g/m\^2) cytarabine during the Screening Phase to control hyperleukocytosis. These treatments must be discontinued greater than or equal to (\>=) 24 hours prior to start of study drug. Empiric all trans retinoic acid (ATRA) treatment for presumed acute promyelocytic leukemia (APL) is permitted but APL must be ruled out and ATRA must be discontinued \>=24 hours prior to the start of study drug * Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies

Exclusion criteria

* Leukemic involvement of the central nervous system * Eligible for an allogeneic hematopoietic stem cell transplantation at study entry * Received a live, attenuated vaccine within 4 weeks prior to initiation of study drug * A history of human immunodeficiency virus (HIV) antibody positive or tests positive for HIV if tested at screening * Known allergies, hypersensitivity, or intolerance to cusatuzumab, venetoclax, azacitidine, or their excipients (example: mannitol, an excipient of azacitidine)

Design outcomes

Primary

Measure	Time frame	Description
Frequency and Severity of Adverse Events (AEs), Laboratory Abnormalities, and Physical Exam Findings as a Measure of Safety	Up to 42 months	Frequency and severity of AEs, laboratory abnormalities, and physical exam findings will be reported.

Secondary

Measure	Time frame	Description
Serum Concentration of Cusatuzumab	Up to 23 months	Serum concentration of cusatuzumab will be assessed.
Number of Participants with Anti-cusatuzumab Antibodies	Up to 23 months	Number of participants with anti-drug antibodies to cusatuzumab will be reported.
Percentage of Participants with Complete Response (CR)	Up to 42 months	Percentage of participants with complete response based on European Leukemia Network (ELN) 2017 response criteria assessment will be reported.
Percentage of Participants with Complete Remission with Partial Hematological Recovery (CRh)	Up to 42 months	Percentage of participants with CRh will be reported based on ELN 2017 response criteria assessment.
Percentage of Participants with CR with Incomplete Recovery (CRi)	Up to 42 months	Percentage of participants with CRi will be reported based on ELN 2017 response criteria assessment.
Percentage of Participants with CR plus CRh	Up to 42 months	Percentage of participants with CR plus CRh will be reported based on ELN 2017 response criteria assessment.
Overall Response Rate (ORR)	Up to 42 months	ORR is defined as percentage of participants with CR, CRh and CRi based on ELN 2017 response criteria assessment.
Percentage of Participants with CR without MRD	Up to 42 months	Percentage of participants with CR without minimal residual disease (MRD) will be reported and is defined as less than (\<) 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level \<10\^-3).
Percentage of Participants with Negative MRD who Achieved CR, CRh, CRi, or Morphologic Leukemia-free State (MLFS)	Up to 42 months	Percentage of participants with negative MRD who achieved CR, CRh, CRi, or MLFS will be reported and is defined as \< 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level \<10\^-3).
Cohort 2 and 3: Time to Response	Up to 42 months	Time to response is defined as time from first dose to achieving the first response of CR, CRh, or CRi.
Cohort 2 and 3: Duration of Response	Up to 42 months	Duration of response is defined as time from achieving the first response of CR, CRh, or CRi to hematologic relapse or death of any cause.
Cohort 2 and 3: Red Blood Cell (RBC) or Platelet Transfusion Independence	Up to 42 months	Transfusion independence (RBC or platelets) is defined as a period of greater than or equal to (\>=) 56 consecutive days with no transfusion between first dose of study drug and the last dose of study drug +30 days.

Countries

Canada, Germany, Poland, Switzerland, United States

Contacts

STUDY_DIRECTORClayton Smith, MD

OncoVerity, Inc.

Outcome results

None listed