CD123 positive Acute Myeloid Leukemia MedDRA version: 20.0 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: IMGN632
Product Code: IMGN632
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: IMGN632
Current S
Sponsors
ImmunoGen, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient must be = 18 years of age. 2. Patients must have confirmed diagnosis of AML (excluding acute promyelocytic leukemia) based on World Health Organization classification. 3. Disease characteristics and allowable prior therapy: a. Patients must be evaluated for any available standard of care therapies and, in the opinion of the treating physician, be deemed appropriate for this experimental therapy. b. Treatment-naïve (untreated) patients will be allowed in the Expansion Phase for Regimens A (IMGN632 + azacitidine) and C (IMGN632 + azacitidine + venetoclax). No prior treatments with HMAs for MDS are allowed. c. Patients must have CD123-positive AML as confirmed by local flow cytometry (or immunohistochemistry [IHC]). d. Patients may have received prior CD123-targeted therapies, except IMGN632, as long as CD123 remains detectable during screening. e. Relapsed AML patients will be allowed to enroll in the Escalation Phase of Regimens A, B, and C (IMGN632 + azacitidine, venetoclax, or azacitidine + venetoclax, respectively) and the Expansion Phase of Regimens A and B and may have received up to 2 prior lines of therapy, eg, frontline treatment (induction, consolidation [including transplant], and maintenance) and 1 salvage regimen. f. Patients enrolling in Regimen D must be in CR (CR/CRi) for no more than 6 months and be MRD+, confirmed by central laboratory testing, after intensive induction/consolidation therapy. 4. Patients enrolling on Regimen D (MRD+ AML), must first have an evaluable screening bone marrow sample confirmed as MRD+ by central flow testing of MRD. 5. Eastern Cooperative Oncology Group performance status = 1. If nonambulatory due to a chronic disability, must be Karnofsky performance status > 70. 6. Previous treatment-related toxicities must have resolved to Grade 1 or baseline (excluding alopecia). 7. Total white blood cell count must be less than 25 x 10e9 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. 8. Liver enzymes (AST and ALT) = 3 × the upper limit of normal (ULN). 9. Total bilirubin = 1.5 × the ULN within 14 days of enrollment. 10. Serum creatinine = 1.5 mg/dL within 14 days of enrollment. 11. Echocardiogram or multigated acquisition scan (MUGA) demonstrating an ejection fraction = 45%. 12. Patients with prior autologous and 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, and the patient must be off all systemic immunosuppression for at least 2 weeks before dosing. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of su
Exclusion criteria
Exclusion criteria: 1. 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. 2. Patients who have been previously treated with IMGN632. 3. Patients with myeloproliferative neoplasm–related secondary AML are excluded from the Dose Expansion Phase of the study. 4. 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. 5. Patients with a history of sinusoidal obstruction syndrome/venous occlusive disease of the liver. 6. 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. 7. 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). 8. Patients who have undergone a major surgery within 4 weeks (or longer if not fully recovered) before study enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1. Safety and Tolerability are assessed throughout the study and at the end of the treatment and end of the study 2. Anti-tumor activity data will be collected at the end of each cycle until a response or progression has reached. ; Main Objective: 1. Dose Escalation Cohorts: Evaluate the safety and tolerability and identify an RP2D of IMGN632 when administered in combination with azacitidine (Regimen A), venetoclax (Regimen B), azacitidine+venetoclax (Regimen C) in patients with relapsed AML. 2. Dose Expansion Cohorts: a. Assess preliminary antileukemia activity of IMGN632 when administered in combination with azacitidine (Regimen A), venetoclax (Regimen B), azacitidine+venetoclax (Regimen C) in patients with either relapsed or untreated AML and assess MRD levels. b. Regimen D (IMGN632 monotherapy in MRD + maintenance): Assess preliminary antileukemia activity of IMGN632 when administered as monotherapy in patients with MRD + AML after frontline therapy ; Secondary Objective: Dose Escalation Cohorts (Regimen A, B and C) 1. Evaluate the safety and tolerability of IMGN632 when administered in combination with azacitidine (Regimen A), venetoclax (Regimen B), azacitidine + venetoclax (Regimen C) in patients with AML 2. Characterize the PK of IMGN632 in combination with azacitidine (Regimen A), venetoclax (Regimen B), azacitidine + venetoclax (Regimen C) 3. Evaluate azacitidine, venetoclax and azacitidine + venetoclax concentrations when administered in combination with IMGN632 4. Characterize the immunogenicity of IMGN632 5. Assess MRD levels during the Escalation Phase Dose Expansion Cohort: Regimen D (IMGN632 monotherapy in MRD+ maintenance) 1. Evaluate the safety and toler | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Dose Escalation+ Dose Expansion Cohorts a. Regimen A (IMGN632+azacitidine), Regimen B (IMGN632+ venetoclax), Regimen C (IMGN632+ azacitidine+venetoclax ) i. TEAEs ii. IMGN632 PK parameters for intact ADC, total antibody, and free payload (FGN849) include, but are not limited to, Cycle 1 and Cycle 3 maximum plasma concentration (Cmax), area under the time-concentration curve (AUC), terminal half-life (t½), clearance (CL), volume of distribution at steady state (Vss), and time that Cmax occurs (tmax) iii. Blood concentration of azacitidine, venetoclax, azacitidine and venetoclax measured before and after their administration iv. ADA response v. MRD levels using central flow cytometry–based testing during dose escalation b. Regimen D (IMGN632 monotherapy in MRD+ maintenance) i. IMGN632 PK parameters for intact ADC, total antibody, and free payload (FGN849) include, but are not limited to, Cycle 1 and Cycle 3 Cmax, AUC, t½, CL, Vss, and tmax ii. ADA response ; Timepoint(s) of evaluation of this end point: 1. Safety and Tolerability are assessed throughout the study and at the end of the treatment and end of the study 2. Anti-tumor activity data will be collected at the end of each cycle until a response or progression has reached. | — |
Countries
France, Germany, Italy, Spain, United Kingdom, United States
Contacts
Public ContactKen Dhimitri
ImmunoGen, Inc.
Outcome results
None listed