A Study of Mirvetuximab Soravtansine in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression

Launched by IMMUNOGEN, INC. · Mar 3, 2020

Keywords

ClinConnect Summary

This study is designed to evaluate the efficacy and safety of mirvetuximab soravtansine (MIRV) in participants with platinum-resistant high-grade serous epithelial ovarian cancer, primary peritoneal, or fallopian tube cancer, whose tumors express a high-level of Folate Receptor Alpha (FRα). Participants will be, in the opinion of the Investigator, appropriate for single-agent therapy for their next line of therapy. FRα positivity will be defined by the Ventana FOLR1 (Folate Receptor 1/Folate Receptor Alpha) Assay.

Approximately 110 eligible participants will be enrolled to achieve a total ...

Gender

FEMALE

Eligibility criteria

• Inclusion Criteria:
• • 1. Female participants ≥ 18 years of age
• • 2. Participants must have a confirmed diagnosis of high-grade serous epithelial ovarian cancer (EOC), primary peritoneal cancer, or fallopian tube cancer
• 3. Participants must have platinum-resistant disease:
• • 1. Participants who have only had 1 line of platinum based therapy must have received at least 4 cycles of platinum, must have had a response (complete response/remission \[CR\] or partial response/remission \[PR\]) and then progressed between \> 3 months and ≤ 6 months after the date of the last dose of platinum
• • 2. Participants who have received 2 or 3 lines of platinum therapy must have progressed on or within 6 months after the date of the last dose of platinum
• • 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
• • Note: Participants who are platinum refractory during front-line treatment are excluded (see exclusion criteria)
• • 4. Participants must have progressed radiographically on or after their most recent line of anticancer therapy.
• • 5. Participants must be willing to 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 Folate Receptor α (FRα) positivity
• • 6. Participant's tumor must be positive for FRα expression as defined by the Ventana FOLR1 Assay
• • 7. Participants must have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the Investigator)
• 8. Participants must have received at least 1 but no more than 3 prior systemic lines of anticancer therapy, including at least 1 line of therapy containing bevacizumab, and for whom single-agent therapy is appropriate as the next line of treatment:
• • 1. Adjuvant ± neoadjuvant considered 1 line of therapy
• • 2. Maintenance therapy (e.g., bevacizumab, poly adenosine diphosphate-ribose polymerase (PARP) inhibitors) will be considered part of the preceding line of therapy (i.e., not counted independently)
• • 3. Therapy changed due to toxicity in the absence of progression will be considered part of the same line (i.e., not counted independently)
• • 4. Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance
• • 9. Participants must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
• 10. Participants must have completed prior therapy within the specified times below:
• • 1. Systemic antineoplastic therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to first dose of MIRV
• • 2. Focal radiation completed at least 2 weeks prior to first dose of MIRV
• • 11. Participants must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia)
• • 12. Participants must have completed any major surgery at least 4 weeks prior to first dose of MIRV and have recovered or stabilized from the side effects of prior surgery
• 13. Participants must have adequate hematologic, liver and kidney functions defined as:
• • 1. Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (1,500/μL) without G-CSF in the prior 10 days or long-acting WBC growth factors in the prior 20 days
• • 2. Platelet count ≥ 100 x 10\^9/L (100,000/μL) without platelet transfusion in the prior 10 days
• • 3. Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 21 days
• • 4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
• • 5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
• • 6. Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin \< 3.0 x ULN)
• • 7. Serum albumin ≥ 2 g/dL
• • 14. Participants or their legally authorized representative must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements
• • 15. Women of childbearing potential (WCBP) must agree to use highly effective contraceptive method(s) while on MIRV and for at least 3 months after the last dose
• • 16. WCBP must have a negative pregnancy test within the 4 days prior to the first dose of MIRV
• Exclusion Criteria:
• • 1. Male participants
• • 2. Participants with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade/borderline ovarian tumor
• • 3. Participants with primary platinum-refractory disease, defined as disease that did not respond to (CR or PR) or has progressed within 3 months of the last dose of first-line platinum-containing chemotherapy
• • 4. Participants with prior wide-field radiotherapy (RT) affecting at least 20 percent of the bone marrow
• • 5. Participants with \> Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE)
• • 6. 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, and /or monocular vision
• 7. Participants with serious concurrent illness or clinically relevant active infection, including, but not limited to the following:
• • 1. Active hepatitis B or C infection (whether or not on active antiviral therapy)
• • 2. Human immunodeficiency virus (HIV) infection
• • 3. Active cytomegalovirus infection
• • 4. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks prior to the first dose of MIRV
• • Note: Testing at screening is not required for the above infections unless clinically indicated
• • 8. Participants with a history of multiple sclerosis (MS) or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
• 9. 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
• • 10. Participants with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment
• • 11. Participants with a history of cirrhotic liver disease (Child-Pugh Class B or C)
• • 12. Participants with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis
• • 13. Participants requiring use of folate-containing supplements (eg, folate deficiency)
• • 14. Participants with prior hypersensitivity to monoclonal antibodies (mAb)
• • 15. Women who are pregnant or breastfeeding
• • 16. Participants who received prior treatment with MIRV or other FRα-targeting agents
• • 17. Participants with untreated or symptomatic central nervous system (CNS) metastases
• • 18. Participants with a history of other malignancy within 3 years prior to 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
• • 19. Prior known hypersensitivity reactions to study drugs and/or any of their excipients