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Also known as CD123-targeted ADC
IMGN632 · 2 trials · 3 indications
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.
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.
Assess Minimal Residual Disease Levels using central flow cytometry-based testing.
CCR rate was defined as percentage of participants with complete remission/response (CR) and clinical complete remission (CRc). CR was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/microliter \[μL\]) and platelet count (≥ 100,000/μL); absence of leukemic blasts; 100% clearance of all skin lesions from baseline; no new lesions in participants without lesions at baseline; nodal masses regression to normal size on computed tomography (CT); and spleen and liver not palpable and nodules disappeared. CRc was defined as normalization of blast percentage (≤ 5%); normalization of neutrophil count (≥ 1000/μL) and platelet count (≥ 100,000/μL); absence of leukemic blasts; marked clearance of all skin lesions from baseline, residual hyperpigmentation or abnormality with BPDCN identified on biopsy (or no biopsy performed); nodal masses regression to normal size on CT; and spleen and liver not palpable and nodules disappeared.
| Arm | Type | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| Escalation and Expansion | EXPERIMENTAL | Escalation: IMGN632 was administered by IV on 2 different schedules for participants with relapsed/refractory AML, ALL, or BPDCN. Expansion: IMGN632 was administered by IV: * Cohort 1: Relapsed or refractory BPDCN participants who have received 1-3 prior systemic therapies (incl. tagraxofusp-erzs and/or any other systemic therapy deemed appropriate for the treatment of BPDCN) * Cohort 2: Relapsed AML * Cohort 3: Relapsed or refractory ALL * Cohort 4: Other relapsed or refractory hematologic malignancies * Cohort 5: Relapsed or refractory AML at alternate dose or schedule * Cohort 6: Pivotal cohort for frontline BPDCN participants who have not received prior systemic therapy and participants with frontline BPDCN who have prior or concomitant hematologic malignancy (PCHM) and have not received prior systemic therapy. |
| Name | Type | Description |
|---|---|---|
| Azacitidine | DRUG | Commercially available formulation given subcutaneously (SC) or intravenous (IV) |
| IMGN632 | DRUG | Study formulation given intravenously (IV) |
| Venetoclax | DRUG | Commercially available formulation administered orally |
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 fo...
IMGN632 is an investigational therapy being studied for CD123-positive acute myeloid leukemia and for blastic plasmacytoid dendritic cell neoplasm, including untreated and relapsed or refractory BPDCN. It is also being evaluated in combination with venetoclax and/or azacitidine in adults with AML.
IMGN632 targets CD123, a cell surface receptor found on leukemic cells in acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm. By binding CD123, the small molecule is designed to deliver its cytotoxic payload selectively to CD123-positive cancer cells.
IMGN632 is being developed by AbbVie Inc., which trades on the New York Stock Exchange under the ticker ABBV. AbbVie acquired the asset through its acquisition of ImmunoGen.
IMGN632 is in Phase 1 clinical development. It is investigational and has not been approved by the FDA for any indication. The Phase 1 program is evaluating the drug as monotherapy and in combination regimens in adults with CD123-positive hematologic malignancies.
IMGN632 is being studied in two Phase 1 trials. NCT04086264 evaluates IMGN632 as monotherapy or with venetoclax and/or azacitidine in CD123-positive acute myeloid leukemia, and NCT03386513 evaluates IMGN632 in untreated and relapsed or refractory blastic plasmacytoid dendritic cell neoplasm. Both are active and not recruiting.
The IMGN632 Phase 1 program has enrolled 218 participants in the acute myeloid leukemia trial NCT04086264 and 179 participants in the blastic plasmacytoid dendritic cell neoplasm trial NCT03386513. Both studies are active but no longer recruiting, and they are being conducted across the United States and several European countries.