Antibody Information
General Information of This Antibody
| Antibody ID | ANI0KQQRV |
|||||
|---|---|---|---|---|---|---|
| Antibody Name | Cantuzumab |
|||||
| Organization | ImmunoGen, Inc. |
|||||
| Indication | Solid tumors |
|||||
| Synonyms |
huC242
Click to Show/Hide
|
|||||
| Antibody Type | Monoclonal antibody (mAb) |
|||||
| Antibody Subtype | Humanized IgG1-kappa |
|||||
| Antigen Name | Syndecan-1 (SDC1) |
Antigen Info | ||||
| Click to Show/Hide the Sequence Information of This Antibody | ||||||
| Heavy Chain Sequence |
QVQLVQSGAEVKKPGETVKISCKASDYTFTYYGMNWVKQAPGQGLKWMGWIDTTTGEPTY
AQKFQGRIAFSLETSASTAYLQIKSLKSEDTATYFCARRGPYNWYFDVWGQGTTVTVSSA STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK Click to Show/Hide
|
|||||
| Light Chain Sequence |
DIVMTQSPLSVPVTPGEPVSISCRSSKSLLHSNGNTYLYWFLQRPGQSPQLLIYRMSNLV
SGVPDRFSGSGSGTAFTLRISRVEAEDVGVYYCLQHLEYPFTFGPGTKLELKRTVAAPSV FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Click to Show/Hide
|
|||||
Each Antibody-drug Conjugate Related to This Antibody
Full Information of The Activity Data of The ADC(s) Related to This Antibody
Cantuzumab ravtansine [Phase 2 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Patients Enrolled |
Eligible patients must have histologically confirmed, CanAg-positive (≥75% tumor cells with 2+/3+ staining) non-colorectal/pancreatic solid tumors that are inoperable/metastatic and refractory to standard therapy, excluding those with leptomeningeal or progressive brain disease. Key requirements include ECOG 0-2, adequate organ function (ANC ≥1,500/mm <sup>3</sup>, platelets ≥100,000/mm <sup>3</sup>, creatinine ≤1.5 mg/dL), no active infections, and ≥4-week washout from prior therapies. Strict exclusion criteria address comorbidities, concurrent malignancies, and treatment-related restrictions to ensure patient safety.
Click to Show/Hide
|
||||
| Administration Dosage |
Thirty patients were treated with huC242-DM4, receiving a single intravenous (IV) infusion once every three weeks. Cohorts of 3 patients initially were enrolled on each dose level. Patients have received huC242-DM4 at 18, 36, 60, 90, 126, 168, 223, and 297 mg/m2.
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT00352131 | Clinical Status | PHASE1 | ||
| Clinical Description |
A Phase I Study to Assess the Safety and Pharmacokinetics of huC242-DM4 Administered as a Single Intravenous Infusion Once Every Three Weeks to Subjects With Solid Tumors
|
||||
| Primary Endpoint |
The primary study objectives focus on assessing dose-limiting toxicities and determining the maximum tolerated dose of the investigational agent, with both measures being evaluated throughout the trial duration.
|
||||
| Other Endpoint |
Secondary endpoints involve comprehensive evaluation of toxicity profiles, pharmacokinetic properties, and antitumor activity, all monitored continuously during the trial period to assess treatment safety and preliminary efficacy.
|
||||
| Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
| Patients Enrolled |
ligibility requires histologically confirmed metastatic/locally advanced gastric/GEJ adenocarcinoma (AJCC IIIA-IV) with CanAg-positive expression, ECOG PS<1, one prior chemotherapy line failure, measurable disease per RECIST, and adequate organ function (ANC>1,500/mm <sup>3</sup>, platelets>100,000/mm <sup>3</sup>, creatinine≤1.5xULN). Key exclusions include active infections, grade≥2 neuropathy, CNS metastases, recent malignancies (<2yrs disease-free except non-melanoma skin/cervical CIS/prostate cancer), concurrent anticancer therapies, and significant comorbidities (uncontrolled diabetes, recent MI, heart failure). Reproductive-age patients require negative pregnancy testing and contraception compliance.
Click to Show/Hide
|
||||
| Administration Dosage |
dose of 126 mg/m2 or 168 mg/m2 given as IV once every 3 weeks
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT00620607 | Clinical Status | PHASE2 | ||
| Clinical Description |
A Phase II, Open Label, Multiple Center Study of huC242-DM4 Given as an Intravenous Infusion Once Every Three Weeks to Patients With Metastatic Gastric or Gastroesophageal Junction Carcinomas
|
||||
| Primary Endpoint |
The primary endpoint of the study is assessment of objective response rate, with evaluation conducted annually throughout the trial period to determine treatment efficacy.
|
||||
| Other Endpoint |
Secondary endpoints include duration of response, progression-free survival, safety/tolerability profile, pharmacokinetic analysis, and tumor FDG uptake effects-all monitored continuously during the study to characterize treatment durability, safety, pharmacologic properties, and metabolic impact.
|
||||
| Experiment 3 Reporting the Activity Date of This ADC | [3] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT00620607 | Clinical Status | Phase 2 | ||
| Clinical Description |
A phase 2, open label, multiple center study of HUC242-DM4 given as an intravenous infusion once every three weeks to patients with metastatic gastric or gastroesophageal junction carcinomas.
|
||||
| Experiment 4 Reporting the Activity Date of This ADC | [4] | ||||
| Patients Enrolled |
Metastatic or inoperable colorectal, pancreatic, and other CanAg-expressing tumors who have failed standard therapy (about 95% of pts. had received = 4 prior chemotherapy regimens).
|
||||
| Administration Dosage |
A single intravenous (IV) infusion once every three weeks, 18, 36, 60, 90, 126, 168, 223, and 297 mg/m2.
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT00352131 | Clinical Status | Phase 1 | ||
| Clinical Description |
A phase 1 study to assess the safety and pharmacokinetics of huC242-DM4 administered as a single intravenous infusion once every three weeks to subjects with solid tumors.
|
||||
| Primary Endpoint |
HuC242-DM4 was well tolerated at the 168 mg/m2 dose level. The MTD is not yet defined.
|
||||
| Other Endpoint |
No clinically significant myelosuppression and no formation of antibody to humanized antibody (HAHA) or drug (HADA).
|
||||
| Experiment 5 Reporting the Activity Date of This ADC | [5] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT00352131 | Clinical Status | Phase 1 | ||
| Clinical Description |
A phase 1 study to assess the safety and pharmacokinetics of huC242-DM4 administered as a single intravenous infusion once every three weeks to subjects with solid tumors.
|
||||
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 48.85% | Positive CD138 expression (CD138 +++/++) | ||
| Method Description |
MOLP-8 cells (1.5x107 cells per mouse) suspended in a 50:50 mixture of serum free media and matrigel were injected subcutaneously in the area under the right shoulder in 100 ul. Nine groups (n=6) were treated with a single intravenous injection of ADCs, each at doses of 250 ug/kg.
|
||||
| In Vivo Model | MOLP-8 CDX model | ||||
| In Vitro Model | Plasma cell myeloma | MOLP-8 cells | CVCL_2124 | ||
Cantuzumab mertansine [Phase 1 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [7] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
0%
|
|||
| Patients Enrolled |
Histological documentation of advanced or metastatic epithelial solid tumor which were likely to express the CanAg antigen, that were refractory or resistant to standard chemotherapy, or for which no effective standard therapy exists.
|
||||
| Administration Dosage |
IV infusion at an initial dose of 30 mg/m2, three times per week for three consecutive weeks for a total of nine doses.
|
||||
| Experiment 2 Reporting the Activity Date of This ADC | [8] | ||||
| Patients Enrolled |
Solid malignancies refractory to standard therapy or for whom no standard therapy existed.
|
||||
| Administration Dosage |
IV cantuzumab mertansine was administered at a rate of 1 mg/min for 30 minutes and then increased to 3 mg/min if hypersensitivity phenomena were not observed. Treatment courses were repeated every 3 weeks.
|
||||
B-B4-DM1 [Investigative]
Discovered Using Patient-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [9] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 87.90% | Positive CD138 expression (CD138+++/++) | ||
| Method Description |
The in vivo antitumor activity of B-B4-DM1 was evaluated in a CD138 positive OPM1 and OPM2 MM cells xenograft models. CB-17 SCID mice were inoculated subcutaneously in the interscapular area with 5x106 OPM1 (A-B) or OPM2 (C-D) MM cells. Animals were treated daily intravenously for 3 consecutive days with either vehicle alone (PBS; n = 5), unconjugated B-B4 (13.3 ug/kg; n = 5), B-B4DM1 (150 ug DM1/kg; n = 5), or control huC242-DM1 (150 ug DM1/kg; n = 5).
Click to Show/Hide
|
||||
| In Vivo Model | Multiple myeloma PDX model (PDX: OPM2) | ||||
| In Vitro Model | Multiple myeloma | Multiple myeloma cells | Homo sapiens | ||
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [9] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 27.30% | Positive CD138 expression (CD138+++/++) | ||
| Method Description |
The in vivo antitumor activity of B-B4-DM1 was evaluated in a CD138 positive OPM1 and OPM2 MM cells xenograft models. CB-17 SCID mice were inoculated subcutaneously in the interscapular area with 5x106 OPM1 (A-B) or OPM2 (C-D) MM cells. Animals were treated daily intravenously for 3 consecutive days with either vehicle alone (PBS; n = 5), unconjugated B-B4 (13.3 ug/kg; n = 5), B-B4DM1 (150 ug DM1/kg; n = 5), or control huC242-DM1 (150 ug DM1/kg; n = 5).
Click to Show/Hide
|
||||
| In Vivo Model | CD138-expressing OPM1 MM cells xenograft model | ||||
| In Vitro Model | Multiple myeloma | Multiple myeloma cells | Homo sapiens | ||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [9] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
25 nM
|
Positive CD138 expression (CD138+++/++) | ||
| Method Description |
The inhibitory activity of B-B4-DM1 against cancer cell growth was compared with B-B4 and DM1 against cancer cell growth in vitro. The cells were treated with B-B4-DM1, B-B4 and DM1 for 96 hours.
|
||||
| In Vitro Model | Plasma cell myeloma | MM1.R cells | CVCL_8794 | ||
References