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First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Mirvetuximab Soravtansine in Adults With Ovarian Cancer and Other Folate Receptor 1 (FOLR1)-Positive Solid Tumors

NCT01609556

Description:

The purpose of this study is to test mirvetuximab soravtansine (IMGN853) in participants with ovarian cancer and other FOLR-1 positive tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Mirvetuximab Soravtansine in Adults With Ovarian Cancer and Other Folate Receptor 1 (FOLR1)-Positive Solid Tumors
  • Official Title: A Phase 1, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of IMGN853 in Adults With Ovarian Cancer and Other FOLR1-Positive Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: IMGN853-0401
  • NCT ID: NCT01609556

Conditions

  • Tumors

Interventions

DrugSynonymsArms
Mirvetuximab soravtansineIMGN853Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W)

Purpose

The purpose of this study is to test mirvetuximab soravtansine (IMGN853) in participants with ovarian cancer and other FOLR-1 positive tumors.

Detailed Description

      The study consists of a dose-escalation phase that will evaluate 2 dosing schedules (Schedule
      A and Schedule B) of mirvetuximab soravtansine and up to 5 dose-expansion groups at the
      maximum tolerated dose (MTD). The first 4 escalation cohorts will be single participant
      cohorts. Subsequent escalation cohorts will use a standard 3+3 design, with each cohort
      consisting of 3 or 4 to 6 participants. Data were collected and analysed for the escalation
      and expansion groups by dose schedule and not by individual dose.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W)ExperimentalParticipants will receive mirvetuximab soravtansine intravenous (IV) infusion on Day 1 of every 21-day (every 3 weeks [Q3W]) cycle. Dose escalation for this group schedule will start at 0.15 milligrams per kilogram (mg/kg) and proceed through 7.0 mg/kg. Doses calculated initially based on participant's total body weight (TBW); then from protocol amendment 5 onwards, calculated based on adjusted ideal body weight (AIBW). Participants will continue to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever comes first, or until the sponsor terminate the study.
  • Mirvetuximab soravtansine
Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly)ExperimentalParticipants will receive mirvetuximab soravtansine IV infusion on Days 1, 8, and 15 of every 28-day cycle. Dose escalation for this group schedule will start at 1.1 mg/kg (calculated based on AIBW) and proceed through 2.5 mg/kg. Participants will continue to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever comes first, or until the sponsor terminate the study.
  • Mirvetuximab soravtansine
Dose Expansion:EOC Participants(Mirvetuximab Soravtansine Q3W)ExperimentalParticipants with epithelial ovarian cancer (EOC) will receive mirvetuximab soravtansine 6.0 mg/kg (maximum tolerated dose [MTD]) IV infusion on Day 1 of every 21-day (Q3W) cycle (calculated based on AIBW). Participants will continue to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever comes first, or until the sponsor terminated the study.
  • Mirvetuximab soravtansine
Dose Expansion: EC Participants(Mirvetuximab Soravtansine Q3W)ExperimentalParticipants with endometrial cancer (EC) will receive mirvetuximab soravtansine 6.0 mg/kg (MTD) IV infusion on Day 1 of every 21-day (Q3W) cycle (calculated based on AIBW). Participants will continue to receive mirvetuximab soravtansine (for clinical benefit) until unacceptable toxicity or withdrawal of consent, whichever comes first, or until the sponsor terminate the study.
  • Mirvetuximab soravtansine

Eligibility Criteria

        Inclusion Criteria

          -  Participants with advanced solid tumor that is refractory to standard treatment, for
             which no standard treatment is available, or the participant refuses standard therapy.

          -  Participants must be willing to provide an archival tumor tissue block or slides for
             biomarker analysis.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.

          -  Time from prior therapy:

               1. Systemic anti-neoplastic therapy: five half-lives or four weeks, whichever is
                  shorter (6 weeks for prior nitrosoureas or mitomycin C).

               2. Radiotherapy: wide-field radiotherapy (for example, greater than [>] 30 percent
                  [%] of marrow-bearing bones) completed at least four weeks, or focal radiation
                  completed at least two weeks, prior to starting study drug.

          -  Participants must have recovered or stabilized from all therapy-related toxicities.

          -  Major surgery (not including placement of vascular access device or tumor biopsies)
             must be completed four weeks prior to Day 1. Participants must have recovered or
             stabilized from the side effects prior to study treatment.

          -  Participants must have adequate hematologic, liver and kidney function.

          -  Participants with central nervous system (CNS) disease involvement are eligible if
             they have had brain metastases resected or have received radiation therapy ending at
             least 4 weeks prior to study day 1 and they meet all of the following criteria:
             Residual neurological symptoms less than or equal to (<=) Grade 1; No dexamethasone
             requirement; and Follow-up magnetic resonance imaging (MRI) shows no progression of
             treated lesions and no new lesions appearing.

          -  Participants must be willing and able to sign the informed consent form, and to adhere
             to the study visit schedule and other protocol requirements.

          -  Women of childbearing potential and men must agree to use effective contraceptive
             methods while on study and for at least twelve weeks after the last dose of study
             drug.

          -  Women of childbearing potential must have a negative pregnancy test prior to the first
             dose of study treatment.

        Exclusion Criteria

          -  Grade >1 neuropathy.

          -  Any active or chronic corneal disorder, including, but not limited to the following:
             Sjogren's syndrome, Fuch's corneal dystrophy (requiring treatment), history of corneal
             transplantation, active herpetic keratitis, and also active ocular conditions
             requiring ongoing treatment/monitoring such as wet age-related macular degeneration
             requiring intravitreal injections, active diabetic retinopathy with macular edema,
             presence of papilledema, acquired monocular vision.

          -  Serious concurrent illness, including, but not limited to the following:

               1. Clinically relevant active infection including known active hepatitis B or C,
                  Human Immunodeficiency Virus (HIV) infection, varicella-zoster virus (shingles)
                  or cytomegalovirus infection or any other known concurrent infectious disease,
                  requiring IV antibiotics within 2 weeks of study enrollment.

               2. Significant cardiac disease such as recent myocardial infarction (<=6 months
                  prior to Day 1), unstable angina pectoris, uncontrolled congestive heart failure
                  (New York Heart Association >class II), uncontrolled hypertension (greater than
                  or equal to [>=] Common Terminology Criteria for Adverse Events Version 4.03
                  [CTCAE v4.03] Grade 3), uncontrolled cardiac arrhythmias, severe aortic stenosis,
                  or >=Grade 3 cardiac toxicity following prior chemotherapy.

               3. History of multiple sclerosis or other demyelinating disease, Eaton-Lambert
                  syndrome (para-neoplastic syndrome), history of hemorrhagic or ischemic stroke
                  within the last six months, or alcoholic liver disease.

               4. Previous clinical diagnosis of treatment-related pneumonitis.

          -  Any other concomitant anti-cancer treatment such as immunotherapy, biotherapy,
             radiotherapy, chemotherapy, investigative therapy, or high-dose steroids; however, low
             dose steroids and Luteinizing Hormone Releasing Hormone (LHRH) at doses that have been
             stable for >=14 days are permitted for participants with prostate cancer.

          -  Known hypersensitivity to previous monoclonal antibody therapy or maytansinoids.

          -  Prior history of solid tumor malignancy within the last 3 years except for adequately
             treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ
             breast cancer, in situ prostate cancer (participants must have shown no evidence of
             active disease for 2 years prior to enrollment).

          -  Concomitant administration of folate-containing vitamins.

          -  Participants who have received prior allogeneic or autologous bone marrow transplants.

          -  Women of childbearing potential who are pregnant or breast feeding.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-Escalation Phase: Maximum Tolerated Dose (MTD) of Mirvetuximab Soravtansine
Time Frame:Cycle 1 (21 days)
Safety Issue:
Description:MTD was defined as the highest dose at which 1 or fewer among 6 participants or less than or equal to (<=) 33 percent (%) experienced a dose-limiting toxicity (DLT) (calculated based on adjusted ideal body weight [AIBW]). AIBW was calculated as ideal body weight (IBW) + 0.4 * (actual weight - IBW), where IBW for men was 0.9 * height in centimeters (cm) - 88 and IBW for women was 0.9 * height in cm - 92. DLT was defined as a treatment-emergent adverse event (TEAE) or abnormal laboratory value related to study treatment (that is, assessed as unrelated to disease, intercurrent illness, or concomitant medications), including those TEAEs and abnormal laboratory values that resulted in a failure to meet the criteria for re-treatment.

Secondary Outcome Measures

Measure:Number of Participants With TEAEs
Time Frame:From first dose of study drug up to 28 days after last dose of study drug (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Safety Issue:
Description:An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to study drug. Severity was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 on following scale: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening, Grade 5=death. Serious AEs include death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as any AE that emerged on or after the first dose, and within 28 days of the last dose.
Measure:Number of Participants With Shift From Baseline Grade <=2 in Clinical Laboratory Parameters to Grade 3 or Grade 4 on Study
Time Frame:From first dose of study drug up to 28 days after last dose of study drug (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Safety Issue:
Description:Laboratory parameters included serum chemistry (alanine aminotransferase [ALT]/serum glutamic pyruvic transaminase [SGPT], aspartate aminotransferase [AST]/serum glutamic oxaloacetic transaminase [SGOT], albumin, alkaline phosphatase, bilirubin, calcium, creatinine, glucose, magnesium, phosphorous, potassium, sodium), hematology (hemoglobin, lymphocytes, neutrophils, platelets, white blood cells) and coagulation (international normalized ratio [INR], partial thromboplastin time [PTT]). Clinically significant laboratory values were defined as per NCI CTCAE v.03 Grade 3 or higher. A grading (severity) scale was provided with grades ranging from 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), to 5 (death). Only participants who shifted from a baseline value of Grade <=2 to a post-baseline Grade 3/4 on-treatment, are reported.
Measure:Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings and Vital Signs
Time Frame:From first dose of study drug up to 28 days after last dose of study drug (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Safety Issue:
Description:Physical examination included assessments of general appearance, skin, head (eyes, ears, nose, and throat), neck, lungs, heart, abdomen, back, lymph nodes, extremities, and neurological system. Vital signs included assessment of blood pressure, pulse rate, respiratory rate and body temperature.
Measure:Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)
Time Frame:Baseline up to end of treatment (EOT) (up to maximum 124 weeks)
Safety Issue:
Description:Standard ECGs were performed in triplicate at 2- to 5-minute intervals during the study. A single ECG was performed at the end of treatment visit and as clinically indicated.
Measure:Number of Participants With Treatment-Emergent Ocular AEs
Time Frame:From first dose of study drug up to 28 days after last dose of study drug (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Safety Issue:
Description:Ocular AEs included keratopathy and blurred vision. An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to study drug. TEAEs were defined as any AE that emerged on or after the first dose, and within 28 days of the last dose.
Measure:Maximum Observed Plasma Concentration (Cmax) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D
Time Frame:Cycle 1, 3: Day 1 (pre-infusion; within 10 minutes [min] of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Safety Issue:
Description:Pharmacokinetic (PK) parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Measure:Cmax of Free DM4 and S-Methyl DM4 at RP2D
Time Frame:Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Safety Issue:
Description:PK parameters were calculated using standard non-compartmental methods. PK analysis of free N2'-[4-[(3-carboxypropyl)dithio]-4-methyl-1-oxo-2-sulfopentyl]-N2'-deacetylmaytansine (DM4) and S-methyl DM4 is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Measure:Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D
Time Frame:Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Safety Issue:
Description:PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Measure:AUC0-inf of Free DM4 and S-Methyl DM4 at RP2D
Time Frame:Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Safety Issue:
Description:PK parameters were calculated using standard non-compartmental methods. PK analysis of free DM4 and S-methyl DM4 is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Measure:Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D
Time Frame:Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Safety Issue:
Description:PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Measure:AUClast of Free DM4 and S-Methyl DM4 at RP2D
Time Frame:Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Safety Issue:
Description:PK parameters were calculated using standard non-compartmental methods. PK analysis of free DM4 and S-methyl DM4 is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Measure:Terminal Half-Life (t1/2) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-Methyl DM4 at RP2D
Time Frame:Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Safety Issue:
Description:PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine, total M9346A antibody, DM4, and S-methyl DM4 is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Measure:Clearance (CL) of Mirvetuximab Soravtansine and Total M9346A Antibody at RP2D
Time Frame:Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Safety Issue:
Description:PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Measure:CL of DM4 and S-Methyl DM4 at RP2D
Time Frame:Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Safety Issue:
Description:PK parameters were calculated using standard non-compartmental methods. PK analysis of DM4 and S-methyl DM4 is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Measure:Time to Reach Maximum Observed Concentration (Tmax) of Mirvetuximab Soravtansine, Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D
Time Frame:Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Safety Issue:
Description:PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine, free DM4, S-methyl DM4, and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Measure:Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine Free DM4, S-Methyl DM4, and Total M9346A Antibody at RP2D
Time Frame:Cycle 1, 3: Day 1 (pre-infusion; within 10 min of EOI; 2, 4, 6, 8 hrs post-infusion); Day 2, 3 (24, 48 hrs post-infusion); Day 4 or 5, 8, 15 (24 hrs post-infusion)
Safety Issue:
Description:PK parameters were calculated using standard non-compartmental methods. PK analysis of mirvetuximab soravtansine, free DM4, S-methyl DM4, and total M9346A antibody is presented for a subgroup of participants who received 6.0 mg/kg (RP2D) mirvetuximab soravtansine at Cycle 1 and Cycle 3.
Measure:Objective Response Rate (ORR): Percentage of Participants With Objective Response as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Time Frame:From first dose of study drug until first BOR of CR or PR (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Safety Issue:
Description:ORR was defined as percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). CR: Disappearance of all target or non-target lesions. All pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR: At least 30 percent (%) decrease in the sum of the longest diameters (SoD) of target lesions, taking as reference the baseline SoD.
Measure:Duration of Response (DOR) as Assessed by RECIST v1.1
Time Frame:From the date of first response (CR or PR) until the date of PD (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Safety Issue:
Description:DOR was defined as the time from the date of the first response (CR or PR), whichever was recorded first, until the date of progressive disease (PD). PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. DOR was only defined for participants who had a BOR of CR or PR using the method of Kaplan-Meier.
Measure:Progression-Free Survival (PFS) as Assessed by RECIST v1.1
Time Frame:From first dose of study drug until PD or death whichever occurred first (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Safety Issue:
Description:PFS was defined as the time from initiation of study drug until PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Measure:Time to Progression (TTP) as Assessed by RECIST v1.1
Time Frame:From first dose of study drug until PD (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Safety Issue:
Description:TTP was defined as the time from initiation of study drug until PD, estimated using the method of Kaplan-Meier. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Measure:Number of Participants With Anti-Drug Antibodies (ADA)
Time Frame:Baseline up to follow-up visit (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Safety Issue:
Description:During the conduct of the study, a single immunogenicity assay was developed to concurrently detect human antibodies against all components of mirvetuximab soravtansine, including the humanized anti-FOLR1 antibody, the cleavable disulfide linker, and the cytotoxic maytansinoid, DM4. Therefore, immunogenicity results were reported as ADA titers, and did not distinguish between human anti-drug or anti-human titers.
Measure:Number of Participants With Gynecologic Cancer Intergroup (GCIG) CA-125 Criteria Clinical Responses
Time Frame:From first dose of study drug until CA-125 response (maximum exposure: 36 weeks for dose-escalation Schedule A, 101.3 weeks for dose-escalation Schedule B, 124 weeks for dose-expansion EOC, 33.3 weeks for dose-expansion EC)
Safety Issue:
Description:CA-125 response was defined as at least 50% reduction in CA-125 levels from baseline. The date of response corresponded to the date when the CA 125 level was first reduced by 50%.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:ImmunoGen, Inc.

Trial Keywords

  • FOLR-1 solid tumors

Last Updated

February 17, 2021