IMGN632 as Monotherapy or With Venetoclax and/or Azacitidine for Participants With CD123-Positive Acute Myeloid Leukemia

NCT ID: NCT04086264

Last Updated: 2025-08-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 218 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-06
• Study Completion Date: 2027-02-28

Brief Summary

This is an open-label, multicenter, Phase 1b/2 study to determine the safety and tolerability of IMGN632 and assess the antileukemia activity of IMGN632 when administered in combination with azacitidine and/or venetoclax in participants with relapsed and frontline CD123-positive AML.

Detailed Description

This study explores multiple IMGN632 doses in combination and monotherapy Regimens, including (A - closed to enrollment)) azacitidine, (B-closed to enrollment) venetoclax, (C) azacitidine+venetoclax, and (D- closed to enrollment) monotherapy in MRD+ AML. For combination Regimens A-C, a Phase 1b Dose Escalation Cohort will determine the recommended Phase 2 dose (RP2D) of IMGN632 in that specific combination Regimen, followed by a Phase 2 Dose Expansion Cohort for each combination Regimen to characterize the safety profile further and assess the antileukemia activity of the different combination Regimens.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Regimen A (Closed to Enrollment)

IMGN632, administered intravenously on Day 7 of a 28 day cycle at 0.015 mg/kg, 0.045 mg/kg, or 0.09 mg/kg, in combination with azacitidine, administered subcutaneously or intravenously daily at 75 mg/m2 on Days 1 to 7 of a 28 day cycle. Cycle 1 azacitidine dose in subsequent cohorts may be reduced.

Group Type: EXPERIMENTAL

Azacitidine

Intervention Type: DRUG

Commercially available formulation given subcutaneously (SC) or intravenous (IV)

IMGN632

Intervention Type: DRUG

Study formulation given intravenously (IV)

Regimen B (Closed to Enrollment)

IMGN632, administered intravenously on Day 7 of a 21 day cycle at 0.015 mg/kg, 0.045 mg/kg, or 0.09 mg/kg, in combination with venetoclax, administered orally daily at 100 mg on Day 1, 200mg on Day 2, and 400 mg on the day 3 up to Day 21 of a 21 day cycle. Alternate schedules with reduced venetoclax administration may be explored.

Group Type: EXPERIMENTAL

IMGN632

Intervention Type: DRUG

Study formulation given intravenously (IV)

Venetoclax

Intervention Type: DRUG

Commercially available formulation administered orally

Regimen C-Frontline&Relapsed/Refractory(Closed to Enrollment)

IMGN632, administered intravenously on Day 7 of a 28 day cycle at 0.015 mg/kg or 0.045 mg/ kg, in combination with azacitidine, administered subcutaneously or intravenously daily at 35-75 mg/ m2 given for Days 1 to 7 of a 28 day cycle and venetoclax, administered orally daily at 100 mg on Day 1, 200mg on Day 2, and 400 mg on Day 3 up to Day 28 of a 28 day cycle. Alternate schedules with reduced venetoclax administration or reduced azacitidine dose or administration may be explored.

Group Type: EXPERIMENTAL

Azacitidine

Intervention Type: DRUG

Commercially available formulation given subcutaneously (SC) or intravenous (IV)

IMGN632

Intervention Type: DRUG

Study formulation given intravenously (IV)

Venetoclax

Intervention Type: DRUG

Commercially available formulation administered orally

Regimen D (Closed to Enrollment)

IMGN632, administered intravenously on Day 1 of a 21 day cycle at 0.045 mg/kg, as a monotherapy for Fit and Unfit MRD+ patients.

Group Type: EXPERIMENTAL

IMGN632

Intervention Type: DRUG

Study formulation given intravenously (IV)

Interventions

Azacitidine

Commercially available formulation given subcutaneously (SC) or intravenous (IV)

Intervention Type: DRUG

IMGN632

Study formulation given intravenously (IV)

Intervention Type: DRUG

Venetoclax

Commercially available formulation administered orally

Intervention Type: DRUG

Other Intervention Names

Vidaza; Decitabine; CD123-targeted ADC; Venclexta; Venclyxto

Eligibility Criteria

Inclusion Criteria

• Patient must be ≥ 18 years of age.
• Patients must have confirmed diagnosis of AML (excluding acute promyelocytic leukemia) based on World Health Organization classification (Arber 2016).
• Disease characteristics and allowable prior therapy:

• Patients must be evaluated for any available standard of care therapies (including induction, consolidation chemotherapy and/or transplant) and, in the opinion of the treating physician, be deemed appropriate for this experimental therapy.
• Treatment-naïve (untreated) patients will be allowed in the Expansion Phase for Regimen C (Triplet) (IMGN632 + azacitidine + venetoclax). No prior treatments with hypomethylating agents (HMAs) for MDS are allowed.
• Patients must have CD123-positive AML as confirmed by local flow cytometry (or immunohistochemistry [IHC]).
• Patients may have received prior CD123-targeted therapies, except IMGN632, as long as CD123 remains detectable during screening.
• Relapsed or refractory CD123-positive AML patients will be allowed to enroll in the Escalation Phase of Regimens A, B, and C (Triplet (IMGN632 + azacitidine, venetoclax, or azacitidine + venetoclax, respectively) and relapsed CD123-positive AML patients will be allowed to enroll the Expansion Phase of Regimens A-C. Note: Patients may also have received up to 2 prior lines of therapy, eg, frontline treatment (induction, consolidation [including transplant], and maintenance) and 1 salvage regimen.
• Patients enrolling in Regimen D must be in CR (CR/CRh/CRp/ CRi) and be MRD+ at the time of screening, confirmed by central laboratory testing. Patients may have no more than 2 prior lines of therapy (which may include stem cell transplant), ie, frontline or first salvage. Note: Fit patients who received intensive treatment (eg 3+7, HiDAC) are eligible for Regimen D Cohort D1. Unfit patients who received non-intensive treatment (eg, HMA, low dose cytarabine) are eligible for Regimen D Cohort D2.
• Previous treatment-related toxicities must have resolved to Grade 1 or baseline (excluding alopecia).
• For patients enrolling in Regimens A-D, total WBC count must < 25 × 10^9 cells/L. Hydroxyurea may be used to control blood counts before Cycle 1 Day 1, at the discretion of the treating physician, according to institutional practice. During the Escalation Phase in Regimens A-C, hydroxyurea may also be used during Cycle 1.
• Liver enzymes (AST and ALT) ≤ 3 × the upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 × the ULN; patients with Gilbert syndrome must have total bilirubin < 3.0 × ULN with direct bilirubin < 1.0 × ULN at the time of enrollment.
• An estimated glomerular filtration rate (eGFR) of > 30 mL/min/1.73 m2 or creatinine clearance of > 30 mL/min.
• Left ventricular ejection fraction (LVEF) ≥ 45% for patients enrolling in Regimens A-D based on locally available assessment, eg, echocardiogram or other modality.
• Patients with prior autologous or allogeneic bone marrow transplant are eligible. Patients with an allogeneic transplant must meet the following conditions: The transplant must have been performed more than 120 days before the date of dosing on this study, the patient must not have active ≥ Grade 2 graft versus host disease (GvHD), or extensive chronic GvHD of any severity, and must be off all immunosuppression for at least 2 weeks prior to first dose of IMGN632.
• Participants or their legally authorized representative must voluntarily sign and date an informed consent, approved by an Institutional Review Board/Independent Ethics Committee (IRB/IEC), before performance of any study-related procedure not part of normal medical care.
• Women of childbearing potential (WCBP), defined as sexually mature women who have not undergone surgical sterilization or who have not been naturally postmenopausal for at least 12 consecutive months (ie, who have had menses any time in the preceding 12 consecutive months), must agree to use acceptable contraceptive methods while on study drug and for at least 7 months after the last dose of IMGN632.
• WCBP must have a negative pregnancy test within 3 days before the first dose of study drug.
• Male patients who are able to father children must agree to use acceptable methods of contraception throughout the study and for at least 4 months after the last dose of study drug(s).
• Patients with prior malignancy are eligible; however, the patient's malignancy must be well-controlled or stable and have completed all systemic chemotherapy and radiotherapy for the prior malignancy at least 6 months before enrollment, and all treatment-related toxicities must have resolved to ≤ Grade 1 (excluding alopecia). Note: patients with prostate cancer or breast cancer on adjuvant hormonal therapy are eligible and may or may not be on long-term maintenance treatment that is unlikely to interfere with study therapy. Note: patients with tumors with a negligible risk for metastasis or death (eg, adequately controlled basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast) are eligible.
• Patients in expansion Cohorts C1 and C2 must be considered ineligible for intensive induction therapy defined by the following:

• ≥ 75 years of age OR
• < 75 years of age with at least one of the following co-morbidities documented within 28 days of Cycle 1 Day 1:
• ECOG performance status of 2 or 3
• History of congestive heart failure requirement treatment or ejection fraction ≤ 50% or chronic stable angina
• Diffusing capacity of the lung for carbon monoxide ≤ 65% or forced expiratory volume in 1 second ≤ 65%
• Creatinine clearance ≥ 30 mL/min to < 45 mL/min
• Moderate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0 × ULN
• Patients in Cohort C1 and C2 must have an ECOG performance status of 0 to 2 for those ≥ 75 years of age OR 0 to 3 for < 75 years of age.
• Patients must not be incarcerated and must be freely willing and able to provide informed consent. Examples of patients unable to freely provide informed consent may include some adults under legal protection measure (eg, under guardianship/curatorship) or unable to express their consent and select adults under psychiatric care. Investigator's discretion should be applied.

Exclusion Criteria

• Patients who have received any anticancer therapy, including investigational agents, within 14 days (or within 28 days for checkpoint inhibitors) before drug administration on this study (hydroxyurea is allowed before beginning study treatment). Patients must have recovered to baseline from all acute toxicity from this prior therapy.
• Patients who have been previously treated with IMGN632.
• Patients with myeloproliferative neoplasm-related secondary AML are excluded from the Dose Expansion Phase of the study.
• Patients with active central nervous system (CNS) AML will be excluded. A lumbar puncture does not need to be performed unless there is clinical suspicion of CNS involvement per investigator judgement. Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS AML is allowed with the approval of the sponsor.
• Patients with a history of sinusoidal obstruction syndrome/venous occlusive disease of the liver.
• Myocardial infarction within 6 months before enrollment or New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities before study entry.
• Clinically relevant active infection including known active hepatitis B or C, HIV infection, or cytomegalovirus or any other known concurrent infectious disease that, in the judgment of the investigator, would make a patient inappropriate for enrollment into this study (testing not required).
• Patients who have undergone a major surgery within 4 weeks (or longer if not fully recovered) before study enrollment.
• Serious or poorly controlled medical conditions that could be exacerbated by treatment or that would seriously compromise safety assessment or compliance with the protocol, in the judgment of the investigator.
• Women who are pregnant or breastfeeding
• Prior known hypersensitivity reactions to monoclonal antibodies (≥ Grade 3).
• Prior known hypersensitivity reactions to study drugs and/or any of their excipients.
• Patients who have a history of allergy to IMGN632 (or any of its excipients), azacitidine, or venetoclax.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

City of Hope National Medical Center /ID# 269273

Duarte, California, United States

University Of California Irvine Medical Center /ID# 269275

Orange, California, United States

Moffitt Cancer Center /ID# 269269

Tampa, Florida, United States

Northwestern University- Robert H. Lurie Comprehensive Cancer Center /ID# 269642

Chicago, Illinois, United States

Dana-Farber Cancer Institute /ID# 269267

Boston, Massachusetts, United States

University of Michigan /ID# 269079

Ann Arbor, Michigan, United States

Mayo Clinic Hospital Rochester /ID# 269643

Rochester, Minnesota, United States

Roswell Park Cancer Institute /ID# 269266

Buffalo, New York, United States

New York Presbyterian Hospital Weill Cornell Medical Center /ID# 269271

New York, New York, United States

Duke University Health System /ID# 269268

Durham, North Carolina, United States

Cleveland Clinic - Cleveland /ID# 269272

Cleveland, Ohio, United States

MD Anderson Houston /ID# 269265

Houston, Texas, United States

Fred Hutchinson Cancer Research Center /ID# 269270

Seattle, Washington, United States

Institut Paoli-Calmettes /ID# 269080

Marseille, Bouches-du-Rhone, France

IUCT Oncopole /ID# 269284

Toulouse, Occitanie, France

Hôpital Saint-Louis /ID# 269282

Paris, Paris, France

Centre Antoine-Lacassagne /ID# 269285

Nice, Provence-Alpes-Côte d'Azur Region, France

Hospices Civils de Lyon - Centre Hospitalier Lyon-Sud /ID# 269286

Pierre-Bénite, Rhone, France

Centre Hospitalier de Versailles André Mignot /ID# 269287

Le Chesnay, , France

Universitaetsklinikum Ulm /ID# 269686

Ulm, Baden-Wurttemberg, Germany

Universitaetsklinikum Muenster /ID# 269688

Münster, North Rhine-Westphalia, Germany

Universitaetsklinikum Leipzig /ID# 269682

Leipzig, Saxony, Germany

IRCCS AOU di Bologna Policlinico Sant Orsola Malpighi /ID# 269281

Bologna, Bologna, Italy

Istituto Europeo Di Oncologia /ID# 269646

Milan, Milano, Italy

Azienda Ospedaliero Universitaria Maggiore Della Carità /ID# 269280

Novara, Novara, Italy

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST - IRCCS /ID# 269279

Meldola, Reggio Emilia, Italy

Hospital MD Anderson Cancer Center Madrid /ID# 269641

Madrid, Madrid, Spain

Hospital Universitario y Politecnico La Fe /ID# 269278

Valencia, Valencia, Spain

Oxford University Hospital NHS Trust /ID# 269647

Oxford, Oxfordshire, United Kingdom

Countries

United States; France; Germany; Italy; Spain; United Kingdom

Related Links

https://www.abbvieclinicaltrials.com/study/?id=IMGN632-0802

Related Info

Other Identifiers

2024-514197-50-00

Identifier Type: OTHER

Identifier Source: secondary_id

IMGN632-0802

Identifier Type: -

Identifier Source: org_study_id