Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0GKOZH
ADC Name
Mirvetuximab soravtansine
Brand Name
Elahere
Synonyms
IMGN853; M9346A-sulfo-SPDB-DM4; Anti-FOLR1 monoclonal antibody-maytansinoid conjugate; MIRV;HDM2002;IMGN-853;M9346-Asulfo-SPDB-DM4;M9346A-sSPDB-DM4;M9346A-sulfo-SPDB-DM4;Anti-FOLR1-monoclonal-antibody-maytansinoid-conjugate-IMGN-853;Mirvetuximab soravtansine-gynx
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Organization
ImmunoGen, Inc.; Hangzhou Zhongmeihuadong Pharmaceutical Co., Ltd.
Drug Status
Approved (FDA): Nov 14, 2022
Indication
In total 9 Indication(s)
Platinum resistant epithelial ovarian cancer [ICD11:2B5D]
Approved
Platinum resistant fallopian tube cancer [ICD11:2C74]
Approved
Platinum resistant peritoneal cancer [ICD11:2C51]
Approved
Epithelial ovarian cancer [ICD11:2B5D]
Phase 3
Fallopian tube cancer [ICD11:2C74]
Phase 3
Peritoneal cancer [ICD11:2C51]
Phase 3
Platinum resistant ovarian cancer [ICD11:2C73]
Phase 3
Endometrial cancer [ICD11:2C76]
Phase 2
Ovarian cancer [ICD11:2C73]
Phase 2
Drug-to-Antibody Ratio
3.4
Structure
Antibody Name
Mirvetuximab
  Antibody Info 
Antigen Name
Folate receptor alpha (FOLR1)
  Antigen Info 
Payload Name
Mertansine DM4
  Payload Info 
Therapeutic Target
Microtubule (MT)
  Target Info 
Linker Name
Sulfo-SPDB
  Linker Info 
Conjugate Type
Random conjugation through nucleophilic lysines.
Combination Type
Soravtansine
Absorption
For mirvetuximab soravtansine-gynx (6 mg/kg), mean Cmax was 137.3 (ug/mL) and mean AUC was 20.65 (mg x h/mL) following the first treatment cycle (21 days). For unconjugated DM4, mean Cmax was 4.11 (ng/mL) and mean AUC was 530 (ng x h/mL) following the first treatment cycle (21 days). For S-methyl-DM4, mean Cmax was 6.98 (ng/mL) and mean AUC was 1848 (ng x h/mL) following the first treatment cycle (21 days). The peak concentration of mirvetuximab soravtansine-gynx was observed near the end of intravenous infusion, while DM4 and S-methyl-DM4 concentrations peaked 2 and 3 days after administration.
Distribution
Mirvetuximab soravtansine-gynx has a steady-state volume of distribution of 2.63 L. Based on in vitro studies, the plasma protein binding of the mirvetuximab soravtansine-gynx component DM4 and its metabolite S-methyl DM4 is higher than 99%.
Metabolism
The monoclonal antibody portion of this drug is expected to be metabolized by catabolic pathways into small peptides. Unconjugated DM4 is reduced and S-methylated to form S-methyl-DM4. DM4 and S-methyl-DM4 are the main circulating metabolites of mirvetuximab soravtansine-gynx and correspond to approximately 0.4% and 1.4% of mirvetuximab soravtansine-gynx AUCs. Both DM4 and S-methyl-DM4 undergo metabolism by CYP3A4. After the first dose, the geometric mean terminal phase half-life of mirvetuximab soravtansine-gynx is 4.8 days. The geometric mean terminal phase half-lives of the unconjugated DM4 and its metabolite, S-methyl-DM4, are 2.8 and 5.0 days, respectively.
Elimination
Mirvetuximab soravtansine-gynx metabolites S-methyl DM4 and DM4-sulfo-SPDB-lysine were detected in urine within 24 hours. The total plasma clearance of mirvetuximab soravtansine-gynx is 18.9 mL/hour. The unconjugated DM4 has a total plasma clearance of 13.8 L/hour, while its metabolite, S-methyl-DM4, has a total plasma clearance of 4.3 L/hour.
Toxicity
Mirvetuximab soravtansine-gynx can cause severe ocular adverse reactions, including visual impairment, keratopathy (corneal disorders), dry eye, photophobia, eye pain, and uveitis. Ocular adverse reactions occurred in 61% of patients with ovarian cancer treated with ELAHERE.
Special Approval(s)
Priority review(FDA); Accelerated approval(FDA); Fast track(FDA); Orphan drug(FDA)
Puchem SID
472407177 , 252089960 , 319422335 , 473153838 , 347828725 , 350078327 , 312467982 , 385747827 , 405044259
Drugbank ID
DB12489
DrugMap ID
DM5S4LX
TTD ID
D0RP2W
ChEBI ID
CHEMBL3545132
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Click To Hide/Show 3 Activity Data Related to This Level
Standard Type NCT Number Clinical Status Clinical Trial Description
Objective Response Rate (ORR)  NCT02631876
Phase 3
FORWARD I: A randomized, open label phase 3 study to evaluate the safety and efficacy of mirvetuximab soravtansine (IMGN853) versus investigator's choice of chemotherapy in women with folate receptor alpha positive advanced epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer.

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Objective Response Rate (ORR)  NCT04296890
Phase 3
SORAYA: A Phase 3, single arm study of mirvetuximab soravtansine in platinum-resistant, advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression.

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Objective Response Rate (ORR)  NCT02606305
Phase 1b/2
A phase 1b/2 study to evaluate the safety, tolerability and pharmacokinetics of mirvetuximab soravtansine (IMGN853) in combination with bevacizumab, carboplatin, pegylated liposomal doxorubicin, pembrolizumab, or bevacizumab + carboplatin, in adults with folate receptor alpha positive advanced epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.

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Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Standard Type Value Units Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI) 
≈ 99.4
%
Uterine serous carcinomas PDX model (PDX: BIO(K)1)
Tumor Growth Inhibition value (TGI) 
≈ 100
%
Uterine serous carcinomas PDX model (PDX: END(K)265)
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 11 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
≈ 33
%
OV-90 cells
Ovarian adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 45
%
IGROV-1 cells
Ovarian endometrioid adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 64
%
OV-90 cells
Ovarian adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 82
%
OV-90 cells
Ovarian adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 82
%
OVCAR-3 cells
Ovarian serous adenocarcinoma
Tumor Growth Inhibition value (TGI) 
93
%
IGROV-1 cells
Ovarian endometrioid adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 93
%
IGROV-1 cells
Ovarian endometrioid adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 95
%
IGROV-1 cells
Ovarian endometrioid adenocarcinoma
Tumor Growth Inhibition value (TGI) 
99.07
%
KB cells
Human papillomavirus-related endocervical adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 100
%
OVCAR-3 cells
Ovarian serous adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 100
%
OVCAR-3 cells
Ovarian serous adenocarcinoma
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Standard Type Value Units Cell Line Disease Model
Half Maximal Inhibitory Concentration (IC50) 
0.15±0.08
nM
KB cells
Human papillomavirus-related endocervical adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
0.20±0.10
nM
JEG-3 cells
Gestational choriocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
1.00±0.40
nM
IGROV-1 cells
Ovarian endometrioid adenocarcinoma
Half Maximal Inhibitory Concentration (IC50) 
0.2
ug/mL
END-2 cells
Endometrial undifferentiated carcinoma
Half Maximal Inhibitory Concentration (IC50) 
74.6
ug/mL
END-1 cells
Endometrial undifferentiated carcinoma
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Objective Response Rate (ORR) 22.00% High FOLR1 expression (FOLR1+++)
Patients Enrolled
Platinum-resistant epithelial ovarian cancer (EOC); Eligible patients with 1-3 prior lines of therapy and whose tumors were positive for FR expression.
Administration Dosage
6 mg/kg Q3W.
Related Clinical Trial
NCT Number NCT02631876  Clinical Status Phase 3
Clinical Description FORWARD I: A randomized, open label phase 3 study to evaluate the safety and efficacy of mirvetuximab soravtansine (IMGN853) versus investigator's choice of chemotherapy in women with folate receptor alpha positive advanced epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer.
Primary Endpoint
For the ITT population, Kaplan-Meier estimates showed no significant difference (HR, 0.98; 95% Cl, 0.73-1.31; P=0.897) in progression-free survival (PFS) between groups Median PFS was 4.10 and 4.40 months for MIRV and IC chemotherapy, respectively. In the prespecified high FR subgroup, PFS was longer in patients in the MIRV group compared with IC chemotherapy (median, 4.80 months versus 3.30 months; HR, 0.69, 95% CI, 0.48 to 1.00; P = 0.049). Based on the Hochberg procedure used in the statistical analysis plan for the study, this P value did not meet statistical significanceBoth in the ITT group and high FR subgroup, OS were not significantly different.

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Other Endpoint
Mirvetuximab soravtansine vs IC chemotherapy in the ITT group: ORR=22.00% vs 12.00%, P=0.015; cancer antigen-125 (CA-125) responses=51.00% vs 27.00%, P<0001; median PFS2 duration (time from randomization to second disease progression or death)=10.00 vs 8.40 months, HR=0.64, 95% Cl, 0.49-0.84, P<0.001); PRO in the EORTC QLQ-OV28 Abdominal/GI Symptom Subscale=32.00% vs 14.00%, P=0.016; Mirvetuximab soravtansine vs IC chemotherapy in the high FR subset, ORR=24.00% vs 10.00%, P=0.014; cancer antigen-125 (CA-125) responses=53.00% vs 25.00%, P=0.001; median PFS2 duration=10.10 vs 8.40 months, HR=0.56, 95% Cl, 0.39-0.79, P<0.001); PRO in the EORTC QLQ-OV28 Abdominal/GI Symptom Subscale=27.00% vs 13.00%, P=0.143.

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Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Objective Response Rate (ORR) 31.73% High FOLR1 expression (FOLR1+++)
Patients Enrolled
Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression.
Administration Dosage
6 mg/kg Q3W.
Related Clinical Trial
NCT Number NCT04296890  Clinical Status Phase 3
Clinical Description SORAYA: A Phase 3, single arm study of mirvetuximab soravtansine in platinum-resistant, advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression.
Primary Endpoint
Confirmed Overall Response Rate=31.73% [(N=104, 95% Cl, 22.90-41.60), Complete response rate=4.80%, Partial response rate=26.90%].
Other Endpoint
Median duration of response=6.90 months (N=33, 95% Cl 5.60-9.70).
Experiment 3 Reporting the Activity Date of This ADC [3]
Efficacy Data Objective Response Rate (ORR) 39.00% Moderate FOLR1 expression (FOLR1++)
Patients Enrolled
Platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.
Administration Dosage
6 mg/kg (adjusted ideal body weight) once every 3 weeks.
Related Clinical Trial
NCT Number NCT02606305  Clinical Status Phase 1b/2
Clinical Description A phase 1b/2 study to evaluate the safety, tolerability and pharmacokinetics of mirvetuximab soravtansine (IMGN853) in combination with bevacizumab, carboplatin, pegylated liposomal doxorubicin, pembrolizumab, or bevacizumab + carboplatin, in adults with folate receptor alpha positive advanced epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
Primary Endpoint
For AURELIA-type patients (N=16, bevacizumab-naive and 1-2 prior lines of therapy, plus medium/high FRa expression), confirmed ORR=56.00%, median duration of response (mDOR)=12.0 months, median progression-free survival (mPFS) = 9.9 months.
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 99.40% (Day 30) Moderate ROR1 expression (ROR1++)
Method Description
In vivoexperiments comparing the antitumor activity of IMGN853 versus ADC isotype control, PBS and M9346A were conducted using both high grade endometrioid/clear cell xenografts as well as a uterine serous tumor PDX model (BIO (K)1).all treatments were given twice, one week apart by retro-orbital injection at a concentration of 5 mg/kg.
In Vivo Model Uterine serous carcinomas PDX model (PDX: BIO(K)1)
Experiment 2 Reporting the Activity Date of This ADC [4]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 25) Moderate ROR1 expression (ROR1++)
Method Description
In vivoexperiments comparing the antitumor activity of IMGN853 versus ADC isotype control, PBS and M9346A were conducted using both high grade endometrioid/clear cell xenografts as well as a uterine serous tumor PDX model (BIO (K)1).all treatments were given twice, one week apart by retro-orbital injection at a concentration of 5 mg/kg.
In Vivo Model Uterine serous carcinomas PDX model (PDX: END(K)265)
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 11 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 33.00% (Day 5) Positive FOLR1 expression (FOLR1 +++/++)
Method Description
Conjugates of the exemplary anti-FOLR1 antibodies were tested using an established xenograft model of OV-90 cells implanted subcutaneous into SCID mice. Mice were randomized by body weight into treatment groups and treated once post cell inoculation with 25 ug/kg of one of the conjugates listed above or with PBS only.
In Vivo Model OV-90 CDX model
In Vitro Model Ovarian adenocarcinoma OV-90 cells CVCL_3768
Experiment 2 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 45.00% (Day 6) Positive FOLR1 expression (FOLR1 +++/++)
Method Description
Conjugates of the exemplary anti-FOLR1 antibodies were tested using an established xenograft model of IGROV-1 cells implanted subcutaneous into SCID mice. Mice were randomized by body weight into treatment groups and treated once post cell inoculation with 25 ug/kg of one of the conjugates listed above or with PBS only.
In Vivo Model IGROV-1 CDX model
In Vitro Model Ovarian endometrioid adenocarcinoma IGROV-1 cells CVCL_1304
Experiment 3 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 64.00% (Day 26) Positive FOLR1 expression (FOLR1 +++/++)
Method Description
Conjugates of the exemplary anti-FOLR1 antibodies were tested using an established xenograft model of OV-90 cells implanted subcutaneous into SCID mice. Mice were randomized by body weight into treatment groups and treated once post cell inoculation with 50 ug/kg of one of the conjugates listed above or with PBS only.
In Vivo Model OV-90 CDX model
In Vitro Model Ovarian adenocarcinoma OV-90 cells CVCL_3768
Experiment 4 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 82.00% (Day 40) Positive FOLR1 expression (FOLR1 +++/++)
Method Description
Conjugates of the exemplary anti-FOLR1 antibodies were tested using an established xenograft model of OV-90 cells implanted subcutaneous into SCID mice. Mice were randomized by body weight into treatment groups and treated once post cell inoculation with 100 ug/kg of one of the conjugates listed above or with PBS only.
In Vivo Model OV-90 CDX model
In Vitro Model Ovarian adenocarcinoma OV-90 cells CVCL_3768
Experiment 5 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 82.00% (Day 21) Positive FOLR1 expression (FOLR1 +++/++)
Method Description
Conjugates of the exemplary anti-FOLR1 antibodies were tested using an established xenograft model of OVCAR-3 cells implanted subcutaneous into SCID mice. Mice were randomized by body weight into treatment groups and treated once post cell inoculation with 25 ug/kg of one of the conjugates listed above or with PBS only.
In Vivo Model OVCAR-3 CDX model
In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
Experiment 6 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) 93.00% (Day 32) High FOLR1 expression (FOLR1+++; 1,300,000 FOLR1 molecules/cell)
Method Description
Animals with established tumors of about 130 mm3 were treated with intravenous single injection of the M9346A-DM conjugates at 2.5±0.2 mg/kg, equivalent to 51±3 ug conjugated maytansinoid per kg The conjugates were injected on day 7 after cell inoculation.
In Vivo Model Ovarian carcinoma Igrov-1 CDX model
In Vitro Model Ovarian endometrioid adenocarcinoma IGROV-1 cells CVCL_1304
Experiment 7 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 93.00% (Day 41) Positive FOLR1 expression (FOLR1 +++/++)
Method Description
Conjugates of the exemplary anti-FOLR1 antibodies were tested using an established xenograft model of IGROV-1 cells implanted subcutaneous into SCID mice. Mice were randomized by body weight into treatment groups and treated once post cell inoculation with 50 ug/kg of one of the conjugates listed above or with PBS only.
In Vivo Model IGROV-1 CDX model
In Vitro Model Ovarian endometrioid adenocarcinoma IGROV-1 cells CVCL_1304
Experiment 8 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 95.00% (Day 67) Positive FOLR1 expression (FOLR1 +++/++)
Method Description
Conjugates of the exemplary anti-FOLR1 antibodies were tested using an established xenograft model of IGROV-1 cells implanted subcutaneous into SCID mice. Mice were randomized by body weight into treatment groups and treated once post cell inoculation with 100 ug/kg of one of the conjugates listed above or with PBS only.
In Vivo Model IGROV-1 CDX model
In Vitro Model Ovarian endometrioid adenocarcinoma IGROV-1 cells CVCL_1304
Experiment 9 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) 99.07% (Day 30) High FOLR1 expression (FOLR1+++; 4,500,000 FOLR1 molecules/cell)
Method Description
Animals with established tumors of about 130 mm3 were treated with intravenous single injection of the M9346A-DM conjugates at 2.5±0.2 mg/kg, equivalent to 51±3 ug conjugated maytansinoid per kg The conjugates were injected on day 20 after cell inoculation.
In Vivo Model FRalpha-positive KB CDX model
In Vitro Model Human papillomavirus-related endocervical adenocarcinoma KB cells CVCL_0372
Experiment 10 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 75) Positive FOLR1 expression (FOLR1 +++/++)
Method Description
Conjugates of the exemplary anti-FOLR1 antibodies were tested using an established xenograft model of OVCAR-3 cells implanted subcutaneous into SCID mice. Mice were randomized by body weight into treatment groups and treated once post cell inoculation with 50 ug/kg of one of the conjugates listed above or with PBS only.
In Vivo Model OVCAR-3 CDX model
In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
Experiment 11 Reporting the Activity Date of This ADC [5]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 120) Positive FOLR1 expression (FOLR1 +++/++)
Method Description
Conjugates of the exemplary anti-FOLR1 antibodies were tested using an established xenograft model of OVCAR-3 cells implanted subcutaneous into SCID mice. Mice were randomized by body weight into treatment groups and treated once post cell inoculation with 100 ug/kg of one of the conjugates listed above or with PBS only.
In Vivo Model OVCAR-3 CDX model
In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.15±0.08 nM
Method Description
Dilutions of conjugates or unconjugated maytansinoid in the appropriate culture medium were added to wells of 96-well flat-bottomed plates containing 1 x103 cells per well The plates were incubated at 37°C, 6% CO2 for either 5 days (continuos exposure) or for 4 hours followed by 5-day incubation in conjugate-free medium (short exposure). Cell viability was determined by the WST-8 assay in accordance with the manufacturer's protocol, and IC50 were generated using a sigmoidal dose-response (variable slope) nonlinear regression curve fit.

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In Vitro Model Human papillomavirus-related endocervical adenocarcinoma KB cells CVCL_0372
Experiment 2 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.20±0.10 nM
Method Description
Dilutions of conjugates or unconjugated maytansinoid in the appropriate culture medium were added to wells of 96-well flat-bottomed plates containing 1 x103 cells per well The plates were incubated at 37°C, 6% CO2 for either 5 days (continuos exposure) or for 4 hours followed by 5-day incubation in conjugate-free medium (short exposure). Cell viability was determined by the WST-8 assay in accordance with the manufacturer's protocol, and IC50 were generated using a sigmoidal dose-response (variable slope) nonlinear regression curve fit.

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In Vitro Model Gestational choriocarcinoma JEG-3 cells CVCL_0363
Experiment 3 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.00±0.40 nM
Method Description
Dilutions of conjugates or unconjugated maytansinoid in the appropriate culture medium were added to wells of 96-well flat-bottomed plates containing 1 x103 cells per well The plates were incubated at 37°C, 6% CO2 for either 5 days (continuos exposure) or for 4 hours followed by 5-day incubation in conjugate-free medium (short exposure). Cell viability was determined by the WST-8 assay in accordance with the manufacturer's protocol, and IC50 were generated using a sigmoidal dose-response (variable slope) nonlinear regression curve fit.

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In Vitro Model Ovarian endometrioid adenocarcinoma IGROV-1 cells CVCL_1304
Experiment 4 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 0.20 ug/mL Positive ROR1 expression (ROR1+++/++)
Method Description
Cell cytotoxicity was tested with IMGN853, ADC isotype control and M9346A in pure and mixed endometrial endometrioid cell lines harboring high FOLR1 expression.
In Vitro Model Endometrial undifferentiated carcinoma END-2 cells CVCL_B5KE
Experiment 5 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) 74.60 ng/mL Positive ROR1 expression (ROR1+++/++)
Method Description
Cell cytotoxicity was tested with IMGN853, ADC isotype control and M9346A in pure and mixed endometrial endometrioid cell lines harboring high FOLR1 expression.
In Vitro Model Endometrial undifferentiated carcinoma END-1 cells CVCL_B5JE
References
Ref 1 Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primaryanalysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765.
Ref 2 Tisotumab Vedotin Continued Treatment in Patients With Solid Tumors.
Ref 3 Phase Ib study of mirvetuximab soravtansine, a folate receptor alpha (FR)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer. Gynecol Oncol. 2020 May;157(2):379-385.
Ref 4 In Vitro and In Vivo Activity of IMGN853, an Antibody-Drug Conjugate Targeting Folate Receptor Alpha Linked to DM4, in Biologically Aggressive Endometrial Cancers. Mol Cancer Ther. 2018 May;17(5):1003-1011. doi: 10.1158/1535-7163.MCT-17-0930.
Ref 5 Folate receptor 1 antibodies and immunoconjugates and uses thereof; 2011-09-01.
Ref 6 IMGN853, a Folate Receptor- (FR)-Targeting Antibody-Drug Conjugate, Exhibits Potent Targeted Antitumor Activity against FR-Expressing Tumors. Mol Cancer Ther. 2015 Jul;14(7):1605-13.

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