Fallopian Tube Cancer, High Grade Ovarian Cancer, Primary Peritoneal Cancer
Conditions
Keywords
platinum sensitive, folate-receptor alpha expression, antibody-drug conjugate, cancer, ovarian neoplasm, high-grade ovarian
Brief summary
IMGN853-0420 is a multicenter, open-label, phase 2 study of carboplatin plus mirvetuximab soravtansine followed by mirvetuximab soravtansine continuation in folate receptor-alpha positive, recurrent platinum sensitive, high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancer following 1 prior line of platinum-based chemotherapy.
Detailed description
This Phase 2 study is designed to evaluate the efficacy and safety of MIRV in combination with carboplatin followed by MIRV continuation in FRα-positive participants with recurrent platinum-sensitive ovarian cancer (PSOC) following 1 prior line of platinum-based chemotherapy. Upon completion of carboplatin plus MIRV combination chemotherapy (6 cycles), participants without progressive disease will continue on single-agent MIRV. Participants must have confirmation of FRα positivity by the Ventana folate receptor 1 (FOLR1) Assay.
Interventions
DRUGMirvetuximab soravtansine
Mirvetuximab Soravtansine (MIRV) is an investigational antibody drug conjugate designed to selectively kill cancer cells. The antibody (protein) part of MIRV targets tumors by delivering a cell-killing drug to the tumor cells carrying a tumor-associated protein called FRα. It is being developed for the treatment of participants with recurrent platinum-sensitive, high grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with FRα expression. FRα positivity will be defined by the Ventana FOLR1 Assay.
DRUGCarboplatin
Carboplatin is considered to be the treatment agent of choice in relapsed PSOC.
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Must be ≥ 18 years of age. 2. Must have an Eastern Cooperative Oncology Group Performance Status of 0 or 1. 3. Must have a confirmed diagnosis of high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. 4. Must have relapsed after 1 prior line of platinum-based chemotherapy. 5. Must have platinum-sensitive disease defined as radiographic progression greater than 6 months from last dose of platinum-based chemotherapy. Note: Progression should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression. 6. If available locally and is the standard of care, breast cancer susceptibility gene (BRCA) testing on the tumor or prior germline testing is required for eligibility, and will need to be done prior to study entry. Somatic and germline BRCA-positive participants must have received prior treatment with a poly adenosine phosphate-ribose polymerase inhibitor (PARPi) unless documented as clinically contraindicated. 7. Must have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the investigator). 8. Must provide an archival tumor tissue block or slides, or undergo procedure to obtain a new biopsy using a low-risk, medically routine procedure for immunohistochemistry (IHC) confirmation of FRα positivity; FRα-expressing tumors will be defined and classified by the Ventana FOLR1 Assay into low, medium, and high expressions defined as 25%-49%, 50%-74%, and ≥ 75% of tumor cells with PS2+ staining intensity, respectively. Must have confirmation of FRα positivity of ≥ 25% of tumor staining at ≥ 2+ intensity for entry into the study. 9. Must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia) and have discontinued any maintenance therapy at least 4 weeks before the first dose of carboplatin plus MIRV. 10. Must have completed any major surgery at least 4 weeks before the first dose of carboplatin plus MIRV and have recovered or stabilized from the side effects of prior surgery before the first dose of carboplatin plus MIRV. 11. Must have adequate hematologic, liver, and kidney functions defined as: 1. Absolute neutrophil count ≥ 1.5 × 10\^9/ liter(L) (1500/ microliter \[μL\]) without granulocyte colony-stimulating factor or long-acting white blood cell growth factors in the 10 days prior to the Cycle 1 Day 1 (C1D1) dose 2. Platelet count ≥ 100 × 109/L (100,000/μL) without platelet transfusion in the 10 days prior to the C1D1 dose 3. Hemoglobin ≥ 9.0 grams/deciliter (g/dL) without packed red blood cell transfusion in the 14 days prior to the C1D1 dose 4. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) 5. Aspartate aminotransferase and alanine aminotransferase ≤ 3.0 × ULN 6. Serum bilirubin ≤ 1.5 × ULN (participants with documented diagnosis of Gilbert syndrome are eligible if total bilirubin \< 3.0 × ULN) 7. Serum albumin ≥ 2 g/dL 12. Must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements. 13. Females of childbearing potential (FCBP) must agree to use highly effective contraceptive method(s) while on study medication and for at least 3 months after the last dose of MIRV and 6 months after the last dose of carboplatin. 14. FCBP must have a negative pregnancy test within the 4 days prior to the C1D1 dose.
Exclusion criteria
1. Participants with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above types, or low-grade/ borderline ovarian tumor 2. More than one line of prior chemotherapy. Lines of prior anticancer therapy are counted with the following considerations: 1. Neoadjuvant ± adjuvant therapies are considered 1 line of therapy if the neoadjuvant and adjuvant correspond to 1 fully predefined regimen; otherwise, they are counted as 2 prior regimens. 2. Maintenance therapy (eg, bevacizumab, PARPi) will be considered part of the preceding line of therapy (ie, not counted independently). 3. Participants with prior wide-field radiotherapy affecting at least 20% of the bone marrow 4. Participants with \> Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE) 5. Participants with active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/ monitoring, such as uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, or monocular vision 6. Participants with serious concurrent illness or clinically relevant active infection, including, but not limited to the following: 1. Active hepatitis B virus (HBV) or hepatitis C virus (HCV)or C infection (whether or not on active antiviral therapy) 2. HIV infection if inclusion clarifying eligibility for HIV positive participants is not met 3. Active cytomegalovirus infection 4. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks prior to the first dose of carboplatin plus MIRV Note: Testing at screening is not required for the above infections unless clinically indicated. 7. Participants with a history of multiple sclerosis or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome) 8. Participants with clinically significant cardiac disease including, but not limited to, any of the following: 1. Myocardial infarction ≤ 6 months prior to first dose 2. Unstable angina pectoris 3. Uncontrolled congestive heart failure (New York Heart Association \> class II) 4. Uncontrolled ≥ Grade 3 hypertension (per CTCAE) 5. Uncontrolled cardiac arrhythmias 9. Participants with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment 10. Participants with a history of cirrhotic liver disease (Child-Pugh Class B or C) 11. Participants with a previous clinical diagnosis of noninfectious interstitial lung disease, including noninfectious pneumonitis (exception: Grade 1 noninfectious pneumonitis diagnosed on or within 6 weeks after treatment with an immunotherapeutic agent used in the treatment of their malignancy that has resolved per investigator or resolution of the radiologic findings) 12. Participants requiring use of folate-containing supplements (eg, folate deficiency) 13. Participants with prior hypersensitivity to monoclonal antibodies (mAb) 14. Females who are pregnant or breastfeeding 15. Participants who received prior treatment with MIRV or other FRαtargeting agents 16. Participants with untreated or symptomatic central nervous system metastases 17. Participants with a history of other malignancy within 3 years before enrollment Note: Participants with tumors with a negligible risk for metastasis or death (eg, adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin, or carcinoma in situ of the cervix or breast) are eligible. 18. Prior known hypersensitivity reactions or known contraindications to study drugs or any of their excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Up to 3 years | ORR following carboplatin plus MIRV combination as measured by the investigator and assessed according to RECIST v1.1, defined as the proportion of confirmed responders (CR or PR) among participants with FRα expression of ≥ 50% o ORR following carboplatin plus MIRV combination will also be measured, as a sensitivity analysis, by a blinded independent central review (BICR) in the same participant population |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Up to 3 years | DOR, defined as the time from first response to radiological progressive disease (PD) or death, whichever occurs first, following carboplatin plus MIRV followed by MIRV continuation by the investigator and assessed according to RECIST v1.1 among efficacy evaluable participants: * with FRα expression of ≥ 50% of tumor cells with PS2+ staining and * with FRα expression of ≥ 25% of tumor cells with PS2+ staining * DOR in the above populations will also be measured by BICR |
| Progression Free Survival (PFS) | Up to 3 years | PFS as measured by the investigator and by BICR in participants with * FRα expression of ≥ 50% of tumor cells with PS2+ staining and * FRα expression of ≥ 25% of tumor cells with PS2+ staining |
| Overall Response Rate (ORR) | Up to 3 years | ORR, defined as the proportion of confirmed responders (CR or PR) following carboplatin plus MIRV combination, as measured by the investigator and assessed according to RECIST v1.1, among patients with FRα expression of ≥ 25% of tumor cells with PS2+ staining intensity who have measurable disease per RECIST v1.1 at inclusion. o ORR will also be measured by a BICR, as a sensitivity analysis, in the same patient population. |
| Cancer Antigen (CA)-125 Response | Up to 3 years | CA-125 response as measured by the investigator, per Gynecologic Cancer Intergroup (GCIG), in the efficacy evaluable participants with * FRα expression of ≥ 50% of tumor cells with PS2+ staining and * FRα expression of ≥ 25% of tumor cells with PS2+ staining |
| Number of Participants With treatment Emergent Adverse Events (TEAEs) | Up to 3 years | — |
| Overall Survival (OS) | Up to 3 years | OS in participants with * FRα expression of ≥ 50% of tumor cells with PS2+ staining and * FRα of ≥ 25% of tumor cells with PS2+ staining |
Countries
Belgium, Canada, Georgia, Spain, United Kingdom, United States
Outcome results
None listed