Advanced Epithelial Ovarian Cancer, Primary Peritoneal Cancer or Primary Fallopian Tube Cancer MedDRA version: 18.1 Level: PT Classification code 10061269 Term: Malignant peritoneal neoplasm System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.1 Level: PT Classification code 10061328 Term: Ovarian epithelial cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version:
Conditions
Interventions
Product Name: Mirvetuximab soravtansina
Product Code: IMGN853
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Mirvetuximab Soravtansina
CAS Number: 1453084-37-1
Current
Sponsors
ImmunoGen, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must have one of the following pathologically documented, definitively diagnosed tumor types: a. Advanced EOC b. Primary peritoneal cancer c. Fallopian tube cancer 2. Patients must have at least one lesion that meets the definition of measurable according to RECIST v1.1. 3. Patients must have received at least three but not more than four prior systemic treatment regimens a. Adjuvant +/- Neoadjuvant will be considered as one regimen b. Maintenance therapy will be considered to be part of the preceding regimen 4. Patients must be willing to provide an archival tumor tissue block or slides, or fresh biopsy. Eligibility is determined based on the IHC performed on the archival tumor tissue. If archival tisuue is not available, then a fresh tumor biopsy, collected using a non significant risk procedure, may be used in place of archival tumor tissue. Patients who do not have archival tisuue and for whom the only sites of disease would require biopsy procedure considered to be of significant risk, must not be enrolled in the study. 5. Patients must have confirmation of FR? positivity by IHC (> 50% of tumor staining at >2+ intensity). 6. > or = 18 years of age 7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 8. Time from prior therapy: a. Systemic anti-neoplastic therapy: five half-lives or four weeks, whichever is shorter b. Radiotherapy: wide-field radiotherapy (e.g. > 30% of marrow-bearing bones) completed at least four weeks, or focal radiation completed at least two weeks, prior to starting study drug 9. Patients must have stabilized or recovered (Grade 1 or baseline) from all therapy-related toxicities. 10. Major surgery (not including placement of vascular access device or tumor punch/scrape biopsies) must be completed four weeks prior to Day 1. Patients must have recovered or stabilized from the side effects prior to study treatment 11. Patients must have adequate hematologic, liver and kidney function as defined by the following parameters: a. Absolute neutrophil count (ANC) > or = 1.5 x 10^9/L (1,500/?L) b. Platelet count > or = 100 x 10^9/L (100,000/microL); no transfusion within previous 10 days c. Hemoglobin > or = 9.0 g/dL d. Serum creatinine ? 1.5 x upper limit of normal (ULN) or 24-hour creatinine clearance of > or = 60 mL/minute e. AST < or = 2.5 x ULN; ALT < or = 2.5 x ULN f. Serum bilirubin < o = 1.5 x ULN (Patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 x ULN). 12. Patients must be willing and able to sign the informed consent form, and to adhere to the study visit schedule and other protocol requirements. 13. Women of child bearing potential (WCBP), defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months) must agree to use effective contraceptive methods (examples include oral, parenteral, or implantable hormonal contraceptive, intra-uterine device, barrier contraceptive with spermicide, partner?s latex condom or vasectomy) while on study treatment and for at least twelve weeks after the last dose of study drug. 14. WCBP must have a negative pregnancy test prior to the first dose of study treatment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderl
Exclusion criteria
Exclusion criteria: 1. Patients with clear cell or low grade ovarian cancer 2. Patients with > Grade 1 peripheral neuropathy 3. Active or chronic corneal disorder, including but not limited to the following: Sjogren?s syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and also active ocular conditions requiring on-going treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, and acquired monocular vision. 4. Serious concurrent illness or clinically-relevant active infection, including, but not limited to the following: a. Known active hepatitis B or C b. Human Immunodeficiency Virus (HIV) infection c. Varicella-zoster virus (shingles) d. Cytomegalovirus infection e. Any other known concurrent infectious disease, requiring IV antibiotics within 2 weeks of starting study treatment 5. Clinically-significant cardiac disease such as recent myocardial infarction ( class II), uncontrolled hypertension (> o = CTCAE v4.03 Grade 3), prior history of hypertensive crisis or hypertensive encephalopathy, uncontrolled cardiac arrhythmias, clinically-significant vascular disease (e.g., aortic aneurysm, or dissecting aneurysm), severe aortic stenosis, clinically significant peripheral vascular disease, or > o =Grade 3 cardiac toxicity following prior chemotherapy 6. History of multiple sclerosis or other demyelinating disease and/or Eaton-Lambert syndrome (para-neoplastic syndrome) 7. History of hemorrhagic or ischemic stroke within the last 6 months 8. History of cirrhotic liver disease 9. Previous clinical diagnosis of non-infectious pneumonitis 10. Required use of folate ?containing supplements (e.g. folate deficiency) 11. Prior hypersensitivity to monoclonal antibodies 12. Current or recent treatment with another investigational drug within four weeks before first study dose 13. Prior treatment with IMGN853
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Stage 1: -To determine the safety and anti-tumor activity of IMGN853 administered every 3 weeks and every 4 weeks -To select the schedule of IMGN853 to continue in Stage 2 Stage 2: -To compare the objective response rate (ORR) of patients with EOC, primary peritoneal cancer or fallopian tube cancer randomized to IMGN853 or selected standard of care chemotherapy;Secondary Objective: Stage 1: ?To evaluate the pharmacokinetics of IMGN853 ?Assess the immunogenicity of IMGN853 (Anti-drug antibodies, ADA) ?Assess the quality of life using the Fact-O Questionnaire Stage 2: ?To compare the safety and tolerability of IMGN853 with that of selected standard of care chemotherapy ?To compare the progression free survival (PFS), overall survival (OS), duration of response (DOR) of patients randomized to IMGN853 or selected standard of care chemotherapy ?To evaluate the pharmacokinetics of IMGN853 ?Assess the immunogenicity of IMGN853(Anti-drug antibodies, ADA) ?Assess the quality of life using the Fact-O Questionnaire;Primary end point(s): Stage 1 Primary Endpoints ? Treatment-emergent adverse events and clinically significant ? Grade 3 changes in laboratory test results, physical examination, ECGs or vital signs ? Anti-tumor activity as assessed by the number of patients with RECIST 1.1 criteria clinical responses and number of patients with GCIG CA-125 criteria clinical responses ? Objective response rate (ORR) ? Progression free survival (PFS) ? Duration of response (DOR) ? Overall Survival (OS) Stage 2 Number of patients with RECIST 1.1 criteria clinical responses and number of patients with GCIG CA-125 criteria clinical responses (Arm 1 and Arm 2) ? Objective response rate (ORR);Timepoint(s) of evaluation of this end point: Stage 1: Treatment-emergent adverse events - At each study visit ECG: D1 of C1 and C3, End of Treatment and 30-Day Follow up Anti-tumor activity: Evaluation at every 6 weeks (+/- 1 week) for first 24 weeks then every 12 weeks (+/ | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Stage 1: ? PK parameters, such as Cmax, Tmax, AUC, terminal half-life (t½?), clearance (Cl), and volume of distribution at steady state (Vss), for IMGN853 will be calculated if feasible. Otherwise, summary statistics of the concentration of each time point will be presented. ? Immunogenicity of IMGN853: Presence of Anti-drug antibodies, ADA ? Quality of life as assessed using Fact-O Questionnaire Stage 2: ? Treatment-emergent adverse events and clinically significant ? Grade 3 changes in laboratory test results, physical examination, ECGs or vital signs ? Calculation of time to event parameters ? Duration of response (DOR): the time from first objective response (CR/PR) to the time of PD or death among those who have achieved a PR or CR ? Progression-free survival (PFS): the time from the date of first dose until the time of death or PD ? Overall survival (OS): the time from the date of first dose until the date of death ? PK parameters, such as Cmax, Tmax, AUC, t½?, clearance (Cl) and volume of distribution at steady state (Vss), for IMGN853 will be calculated if feasible. Otherwise, summary statistics of the concentration for each time point will be presented. ? Immunogenicity of IMGN853: Presence of Anti-drug antibodies, ADA ? Quality of life as assessed using Fact-O Questionnaire;Timepoint(s) of evaluation of this end point: Stage 1: PK parameters: C1 (D1, D8 and D15), C2 (D1), C3 (D1, D8 and D15), C4 (D1), End of Treatment and 30-Day Follow up Immunogenicity: C1, C2 , C4 and C6 (D1), End of Treatment and 30 Day Follow up Quality of Life: C1 (D1) and C ?4 every 12 weeks and End of Treatment Stage 2: Treatment-emergent adverse events - At each study visit; ECG: D1 of C1 and C3, End of Treatment and 30-Day Follow up Anti-tumor activity: Evaluation at every 6 weeks (± 1 week) for first 24 weeks then every 12 weeks (± 1 week); CA-125: At day 1 of each cycle and at every 6 weeks (± 1 week) for first 24 weeks then every 12 weeks (± 1 w | — |
Countries
Belgium, Bulgaria, France, Germany, Italy, Netherlands, Poland, Spain, United Kingdom, United States
Contacts
Public ContactMarissa Volpe
ImmunoGen, Inc.
Outcome results
None listed