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

NCT04086264 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: IMGN632-08022024-514197-50-00
• Study Type: interventional
• Target: 218
• Locations: 6 countries
• Sites: 29

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.

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; AML; Minimal detectable disease; MRD; CD123; Relapsed/refractory; Frontline

Outcome Measures

Primary Outcomes (3)

• Safety and Tolerability

  Evaluate the safety and tolerability and identify an RP2D of IMGN632 when administered in combination with azacitidine, with venetoclax, and with azacitidine and venetoclax in patients with relapsed or refractory CD123-positive AML through review of Treatment Emergent Adverse Events and abnormal laboratory values that result in a failure to meet the criteria for re-treatment.

  approximately 3 years

• Preliminary antileukemia activity

  Assess preliminary antileukemia activity of IMGN632 when administered as a monotherapy in MRD+ Fit and MRD + Unfit AML patient populations, and in combination with azacitidine, with venetoclax, and with azacitidine and venetoclax in patients with relapsed or untreated AML as assessed by complete response, complete remission with partial hematologic recovery, complete remission with incomplete platelet recovery, morphologic leukemia-free state, partial response, and duration of remission.

  approximately 20 months

• Minimal Residual Disease Levels

  Assess Minimal Residual Disease Levels using central flow cytometry-based testing.

  approximately 18 months

Secondary Outcomes (4)

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs) (Dose Expansion Phase)

  Up to approximately 12 months

• Study Drug Concentration (Dose Escalation and Expansion)

  Up to approximately 12 months

• Anti-drug Antibody Concentration (Dose Escalation and Expansion)

  Up to approximately 12 months

• Minimal Residual Disease Levels (Dose Escalation)

  Up to approximately 7 months

Study Arms (4)

Regimen A (Closed to Enrollment)

EXPERIMENTAL

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.

Drug: Azacitidine; Drug: IMGN632

Regimen B (Closed to Enrollment)

EXPERIMENTAL

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.

Drug: IMGN632; Drug: Venetoclax

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

EXPERIMENTAL

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.

Drug: Azacitidine; Drug: IMGN632; Drug: Venetoclax

Regimen D (Closed to Enrollment)

EXPERIMENTAL

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.

Drug: IMGN632

Interventions

Azacitidine DRUG

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

Also known as: Vidaza, Decitabine

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

IMGN632 DRUG

Study formulation given intravenously (IV)

Also known as: CD123-targeted ADC

Regimen A (Closed to Enrollment); Regimen B (Closed to Enrollment); Regimen C-Frontline&Relapsed/Refractory(Closed to Enrollment); Regimen D (Closed to Enrollment)

Venetoclax DRUG

Commercially available formulation administered orally

Also known as: Venclexta, Venclyxto

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (29)

City of Hope National Medical Center /ID# 269273

Duarte, California, 91010, United States

Location

University Of California Irvine Medical Center /ID# 269275

Orange, California, 92868, United States

Location

Moffitt Cancer Center /ID# 269269

Tampa, Florida, 33612, United States

Location

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

Chicago, Illinois, 60611-3015, United States

Location

Dana-Farber Cancer Institute /ID# 269267

Boston, Massachusetts, 02215, United States

Location

University of Michigan /ID# 269079

Ann Arbor, Michigan, 48109-2800, United States

Location

Mayo Clinic Hospital Rochester /ID# 269643

Rochester, Minnesota, 55905, United States

Location

Roswell Park Cancer Institute /ID# 269266

Buffalo, New York, 14263, United States

Location

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

New York, New York, 10461, United States

Location

Duke University Health System /ID# 269268

Durham, North Carolina, 27705-3976, United States

Location

Cleveland Clinic - Cleveland /ID# 269272

Cleveland, Ohio, 44195, United States

Location

MD Anderson Houston /ID# 269265

Houston, Texas, 77030-4000, United States

Location

Fred Hutchinson Cancer Research Center /ID# 269270

Seattle, Washington, 98109, United States

Location

Institut Paoli-Calmettes /ID# 269080

Marseille, Bouches-du-Rhone, 13273, France

Location

IUCT Oncopole /ID# 269284

Toulouse, Occitanie, 31059, France

Location

Hôpital Saint-Louis /ID# 269282

Paris, Paris, 75010, France

Location

Centre Antoine-Lacassagne /ID# 269285

Nice, Provence-Alpes-Côte d'Azur Region, 06189, France

Location

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

Pierre-Bénite, Rhone, 69310, France

Location

Centre Hospitalier de Versailles André Mignot /ID# 269287

Le Chesnay, 78157, France

Location

Universitaetsklinikum Ulm /ID# 269686

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Universitaetsklinikum Muenster /ID# 269688

Münster, North Rhine-Westphalia, 48149, Germany

Location

Universitaetsklinikum Leipzig /ID# 269682

Leipzig, Saxony, 04103, Germany

Location

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

Bologna, Bologna, 40138, Italy

Location

Istituto Europeo Di Oncologia /ID# 269646

Milan, Milano, 20141, Italy

Location

Azienda Ospedaliero Universitaria Maggiore Della Carità /ID# 269280

Novara, Novara, 28100, Italy

Location

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

Meldola, Reggio Emilia, 47014, Italy

Location

Hospital MD Anderson Cancer Center Madrid /ID# 269641

Madrid, Madrid, 28033, Spain

Location

Hospital Universitario y Politecnico La Fe /ID# 269278

Valencia, Valencia, 46026, Spain

Location

Oxford University Hospital NHS Trust /ID# 269647

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

Azacitidine; Decitabine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2019
• First Posted: September 11, 2019
• Study Start: November 6, 2019
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (4); DE (3); FR (6); GB (1); US (13); ES (2)