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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 (IMGN853-0401)

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ClinicalTrials.gov Identifier: NCT01609556
Recruitment Status : Completed
First Posted : June 1, 2012
Results First Posted : February 17, 2021
Last Update Posted : February 17, 2021
Sponsor:
Information provided by (Responsible Party):
ImmunoGen, Inc.

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

Condition or disease Intervention/treatment Phase
Tumors Drug: Mirvetuximab soravtansine Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 206 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 28, 2012
Actual Primary Completion Date : March 19, 2018
Actual Study Completion Date : March 19, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer

Arm Intervention/treatment
Experimental: Dose Escalation: Schedule A (Mirvetuximab Soravtansine Q3W)
Participants 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.
Drug: Mirvetuximab soravtansine
Mirvetuximab soravtansine IV infusion will be administered as per dose and schedule specified in the respective arms.
Other Name: IMGN853

Experimental: Dose Escalation: Schedule B (Mirvetuximab Soravtansine Weekly)
Participants 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.
Drug: Mirvetuximab soravtansine
Mirvetuximab soravtansine IV infusion will be administered as per dose and schedule specified in the respective arms.
Other Name: IMGN853

Experimental: Dose Expansion:EOC Participants(Mirvetuximab Soravtansine Q3W)
Participants 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.
Drug: Mirvetuximab soravtansine
Mirvetuximab soravtansine IV infusion will be administered as per dose and schedule specified in the respective arms.
Other Name: IMGN853

Experimental: Dose Expansion: EC Participants(Mirvetuximab Soravtansine Q3W)
Participants 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.
Drug: Mirvetuximab soravtansine
Mirvetuximab soravtansine IV infusion will be administered as per dose and schedule specified in the respective arms.
Other Name: IMGN853




Primary Outcome Measures :
  1. Dose-Escalation Phase: Maximum Tolerated Dose (MTD) of Mirvetuximab Soravtansine [ Time Frame: Cycle 1 (21 days) ]
    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.

  2. Dose-Escalation Phase: Recommended Phase 2 Dose (RP2D) of Mirvetuximab Soravtansine [ Time Frame: Cycle 1 (21 days) ]
    RP2D was determined by MTD. MTD was defined as the highest dose at which 1 or fewer among 6 participants or <=33% experienced a DLT. DLT was defined as a 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. Available clinical data indicated that the MTD defined for the Q3W schedule was equal to the RP2D.


Secondary Outcome Measures :
  1. 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) ]
    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.

  2. 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) ]
    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.

  3. 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) ]
    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.

  4. Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) [ Time Frame: Baseline up to end of treatment (EOT) (up to maximum 124 weeks) ]
    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.

  5. 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) ]
    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.

  6. 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) ]
    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.

  7. 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) ]
    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.

  8. 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) ]
    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.

  9. 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) ]
    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.

  10. 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) ]
    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.

  11. 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) ]
    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.

  12. 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) ]
    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.

  13. 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) ]
    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.

  14. 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) ]
    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.

  15. 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) ]
    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.

  16. 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) ]
    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.

  17. 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) ]
    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.

  18. 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) ]
    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.

  19. 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) ]
    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.

  20. 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) ]
    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.

  21. 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) ]
    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.

  22. 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) ]
    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%.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01609556


Locations
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United States, Kansas
University of Kansas Medical Center Research Institute
Fairway, Kansas, United States, 66205
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02062
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
United States, Oklahoma
University of Oklahoma Stephenson Cancer Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
CTRC at the University of Texas Health Science Center
San Antonio, Texas, United States, 78229
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
McGill University Health Centre
Montreal, Quebec, Canada, H4A3J1
Sponsors and Collaborators
ImmunoGen, Inc.
  Study Documents (Full-Text)

Documents provided by ImmunoGen, Inc.:
Study Protocol  [PDF] September 2, 2015
Statistical Analysis Plan  [PDF] February 1, 2018

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Responsible Party: ImmunoGen, Inc.
ClinicalTrials.gov Identifier: NCT01609556    
Other Study ID Numbers: IMGN853-0401
First Posted: June 1, 2012    Key Record Dates
Results First Posted: February 17, 2021
Last Update Posted: February 17, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ImmunoGen, Inc.:
FOLR-1 solid tumors
Additional relevant MeSH terms:
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Maytansine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action