Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0ZIJNR
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| ADC Name |
Milatuzumab doxorubicin
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| Synonyms |
milatuzumab doxorubicin; hLL1-DOX; IMMU-110
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| Organization |
Immunomedics (Top20 MNC) (Originator)
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| Drug Status |
Phase 1/2 (discontinued)
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| Drug-to-Antibody Ratio |
8
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| Structure |
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| Antibody Name |
Milatuzumab
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Antibody Info | ||||
| Antigen Name |
HLA class II histocompatibility antigen gamma chain (CD74)
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Antigen Info | ||||
| Payload Name |
Doxorubicin
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Payload Info | ||||
| Therapeutic Target |
DNA topoisomerase 2-alpha (TOP2A)
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Target Info | ||||
| Linker Name |
SMCC-hydrazide
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Linker Info | ||||
| Conjugate Type |
Random Cysteines
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The indication landscape of This ADC(2027 Update)
The clinical trial pipeline of This ADC(2027 Update)
| Indication | Phase 1 | Phase 1/2 | Phase 2 | Phase 2/3 | Phase 3 | New Drug Application | Approved | ||
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| Chronic lymphocytic leukemia |
1 Trials
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| Multiple myeloma |
1 Trials
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| Unspecific non-hodgkin lymphoma |
1 Trials
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General Information of The Activity Data Related to This ADC
Revealed Based on the Cell Line Data
Identified from the Human Clinical Data
Full List of Activity Data of This Antibody-drug Conjugate
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 0.8 uM | Positive CD74 expression (CD74+++/++) | ||
| Method Description |
Briefly, cells were placed in 96-well plates (2 x105 per well) and subsequently incubated with serial dilutions of IMMU-110,naked hLL1,nonspecific negative control mAb-drug conjugate (hRS7-doxorubicin),or nonspecific mAb (hRS7) on ice for 1.5 hours. 4-hour IC50 values of IMMU-110,hRS7-doxorubicin,and free doxorubicin against the multiple myeloma cell line (MC/CAR) and other CD74-positive non-Hodgkin's lymphoma cell lines (Daudi and Raji).
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| In Vitro Model | EBV-related Burkitt lymphoma | Raji cells | CVCL_0511 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 0.9 uM | Positive CD74 expression (CD74+++/++) | ||
| Method Description |
Briefly, cells were placed in 96-well plates (2 x105 per well) and subsequently incubated with serial dilutions of IMMU-110,naked hLL1,nonspecific negative control mAb-drug conjugate (hRS7-doxorubicin),or nonspecific mAb (hRS7) on ice for 1.5 hours. 4-hour IC50 values of IMMU-110,hRS7-doxorubicin,and free doxorubicin against the multiple myeloma cell line (MC/CAR) and other CD74-positive non-Hodgkin's lymphoma cell lines (Daudi and Raji).
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| In Vitro Model | Normal | MC/CAR cells | CVCL_1397 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 1.5 uM | Positive CD74 expression (CD74+++/++) | ||
| Method Description |
Briefly, cells were placed in 96-well plates (2 x105 per well) and subsequently incubated with serial dilutions of IMMU-110,naked hLL1,nonspecific negative control mAb-drug conjugate (hRS7-doxorubicin),or nonspecific mAb (hRS7) on ice for 1.5 hours. 4-hour IC50 values of IMMU-110,hRS7-doxorubicin,and free doxorubicin against the multiple myeloma cell line (MC/CAR) and other CD74-positive non-Hodgkin's lymphoma cell lines (Daudi and Raji).
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| In Vitro Model | Burkitt lymphoma | Daudi cells | CVCL_0008 | ||
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Patients Enrolled |
Eligible patients (≥18 years) must have recurrent B-cell NHL or CLL (≥1 prior therapy), measurable disease, and adequate organ/hematologic function, while excluding those with active HBV/HCV/HIV, heart failure, uncontrolled arrhythmias, recent cardiac events, autoimmune diseases, bulky tumors (>10cm), steroid dependence (>20mg/day prednisone), or pregnancy/lactation. Allogeneic transplant recipients ≥12 weeks post-procedure may enroll.
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| Administration Dosage |
hLL1-DOX is administered intravenously at one of 4 dose levels on days 1, 4, 8 and 11 of 21-day treatment cycles, with up to 8 cycles administered.
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| Related Clinical Trial | |||||
| NCT Number | NCT01585688 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | A Phase I/II Study of Immunotherapy With hLL1-DOX in Patients With Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL) | ||||
| Primary Endpoint |
The study assesses hLL1-DOX's safety profile using NCI CTCAE v4.0 for AE grading and evaluates efficacy through response rates (PR/CR) per dose level, with Kaplan-Meier analysis for progression-free survival (time to progression/death) and duration of response (time from response to relapse), monitoring patients every 3 months for up to 2 years post-treatment.
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| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Patients Enrolled |
Eligibility requires relapsed/refractory MM (≥2 prior therapies including immunomodulators/PIs), measurable disease, Karnofsky ≥70%, and adequate organ function, while excluding transplant candidates, prior anthracycline exposure >300mg/m2, active HIV/HBV/HCV, autoimmune disorders, recent radiation/chemotherapy (14-28 days), or uncontrolled comorbidities. Pregnancy and inadequate contraception are exclusionary.
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| Administration Dosage |
hLL1-DOX will be administered intravenously (through a vein) on days 1, 4, 8 & 11 every 21 days for up to 8 treatment cycles. 4 different dose levels of hLL1-DOX will be studied for safety and tolerability.
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| Related Clinical Trial | |||||
| NCT Number | NCT01101594 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | A Phase I/II Study of hLL1-DOX (Milatuzumab-Doxorubicin Antibody-Drug Conjugate) in Patients With Multiple Myeloma | ||||
| Primary Endpoint |
Safety will be analyzed for all treated patients with intensive monitoring (pre-infusion, every 15min during infusion, plus 30/60/90/120min post-infusion), categorizing AEs by MedDRA v8.0 SOC/Preferred Term and NCI CTC v3 toxicity grades per dose cohort.
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| Other Endpoint |
The efficacy population includes patients receiving ≥1 full dose with response data, evaluating IMWG response rates, response duration, and PFS by descriptive statistics across dose groups, assessed at 4/8/12 weeks then quarterly for 2 years.
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References