Linker Information
General Information of This Linker
| Linker ID |
LIN0WJIST
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| Linker Name |
SMCC-hydrazide
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| Antibody-Linker Relation |
Cleavable
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| Structure |
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Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
Milatuzumab doxorubicin [Phase 1/2 (discontinued)]
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
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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
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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
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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)
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| 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
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| 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