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

Study Overview
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Brief Summary
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This study is designed to evaluate the efficacy and safety of mirvetuximab soravtansine (MIRV) in patients 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). Patients will be, in the opinion of the Investigator, appropriate for single-agent therapy for their next line of therapy. All patients will receive single-agent MIRV at 6 mg/kg adjusted ideal body weight administered on Day 1 of every 3-week cycle.

Detailed Description
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This study is designed to evaluate the efficacy and safety of mirvetuximab soravtansine (MIRV) in patients 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). Patients 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 patients will be enrolled to achieve a total of 105 efficacy evaluable patients. Efficacy evaluable patients include those who have measurable lesions per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) at baseline and received at least 1 dose of MIRV. All patients will receive single-agent MIRV at 6 mg/kg adjusted ideal body weight (AIBW) administered on Day 1 of every 3-week cycle (Q3W). Tumor response will be evaluated by the Investigator using RECIST v1.1. Computerized tomography (CT) or magnetic resonance imaging (MRI) scans will be collected for sensitivity analysis by blinded independent central review (BICR). Patients will continue to receive MIRV until disease progression, unacceptable toxicity, withdrawal of consent, death, or until the Sponsor terminates the study (whichever comes first). Tumor assessments, including radiological assessments by CT/MRI scans will be performed at Screening and subsequently every 6 weeks (± 1 week) from Cycle 1 Day 1 (C1D1) for the first 36 weeks then every 12 weeks (± 3 weeks) until disease progression, death, the start of new anticancer therapy, or patient's withdrawal of consent (whichever occurs first). Patients who discontinue MIRV for reasons other than progressive disease (PD) will continue with tumor assessments until documentation of PD or the start of a new anticancer therapy, whichever comes first. Prior to Week 36 (from Cycle 1, Day 1), assessments should occur every 6 weeks (± 1 week) as allowed by local requirements but must occur at an interval of no more than 12 weeks. After Week 36, assessment will occur every 12 weeks (± 3 weeks) until documentation of PD or the start of new anticancer therapy. All patients who discontinue MIRV will be followed for survival every 3 months (± 1 month) until death, lost to follow-up, withdrawal of consent for survival follow-up, or end of study (EOS) (whichever comes first). Additional survival follow-up calls may occur periodically, if needed.

Official Title
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SORAYA: A Phase 3, Single Arm Study of Mirvetuximab Soravtansine in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression

Conditions
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Epithelial Ovarian Cancer, Peritoneal Cancer, Fallopian Tube Cancer

Intervention / Treatment
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* Drug: Mirvetuximab Soravtansine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients ≥ 18 years of age Patients must have a confirmed diagnosis of high-grade serous epithelial ovarian cancer (EOC), primary peritoneal cancer, or fallopian tube cancer Patients must have platinum-resistant disease: Patients 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 Patients 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: Patients who are platinum refractory during front-line treatment are excluded (see exclusion criteria) Patients must have progressed radiographically on or after their most recent line of anticancer therapy. Patients 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 Patient's tumor must be positive for FRα expression as defined by the Ventana FOLR1 Assay Patients must have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the Investigator) Patients 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: Adjuvant ± neoadjuvant considered 1 line of therapy 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) Therapy changed due to toxicity in the absence of progression will be considered part of the same line (i.e., not counted independently) Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance Patients must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 Patients must have completed prior therapy within the specified times below: Systemic antineoplastic therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to first dose of MIRV Focal radiation completed at least 2 weeks prior to first dose of MIRV Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia) Patients 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 Patients must have adequate hematologic, liver and kidney functions defined as: 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 Platelet count ≥ 100 x 10^9/L (100,000/μL) without platelet transfusion in the prior 10 days Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 21 days Serum creatinine ≤ 1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 x ULN) Serum albumin ≥ 2 g/dL Patients or their legally authorized representative must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements Women of childbearing potential (WCBP) must agree to use highly effective contraceptive method(s) (as defined in Section 5.8.6 of the protocol) while on MIRV and for at least 3 months after the last dose WCBP must have a negative pregnancy test within the 4 days prior to the first dose of MIRV Exclusion Criteria: Male patients Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade/borderline ovarian tumor Patients 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 Patients with prior wide-field radiotherapy (RT) affecting at least 20 percent of the bone marrow Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE) Patients 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 Patients with serious concurrent illness or clinically relevant active infection, including, but not limited to the following: Active hepatitis B or C infection (whether or not on active antiviral therapy) Human immunodeficiency virus (HIV) infection Active cytomegalovirus infection 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 Patients with a history of multiple sclerosis (MS) or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome) Patients with clinically significant cardiac disease including, but not limited to, any of the following: Myocardial infarction ≤ 6 months prior to first dose Unstable angina pectoris Uncontrolled congestive heart failure (New York Heart Association > class II) Uncontrolled ≥ Grade 3 hypertension (per CTCAE) Uncontrolled cardiac arrhythmias Patients with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C) Patients with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis Patients requiring use of folate-containing supplements (eg, folate deficiency) Patients with prior hypersensitivity to monoclonal antibodies (mAb) Women who are pregnant or breastfeeding Patients who received prior treatment with MIRV or other FRα-targeting agents Patients with untreated or symptomatic central nervous system (CNS) metastases Patients with a history of other malignancy within 3 years prior to enrollment. Note: patients 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 Prior known hypersensitivity reactions to study drugs and/or any of their excipients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All patients will receive single-agent MIRV at 6 mg/kg adjusted ideal body weight (AIBW) administered on Day 1 of every 3-week cycle (Q3W)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>All patients will receive single-agent mirvetuximab soravtansine (MIRV) at 6 mg/kg adjusted ideal body weight (AIBW) administered on Day 1 of every 3-week cycle (Q3W). | Drug: Mirvetuximab Soravtansine<br>* Mirvetuximab Soravtansine is an antibody drug conjugate designed to target folate receptor α (FRα). It consists of the humanized anti-FRα mAb M9346A attached via a cleavable disulfide linker to the cytotoxic maytansinoid, DM4.<br>* Other names: MIRV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective response rate (ORR), which includes best response of complete response (CR) or partial response (PR) as assessed by the Investigator. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | The time from initial Investigator-assessed response (CR or PR) until progressive disease (PD) as assessed by the Investigator | Up to 2 years | 
| Adverse Events (AEs) | Adverse Events (AE's) will be evaluated according to the NCI CTCAE v5.0. AE's will be coded using the latest Medical Dictionary for Regulatory Activities (MedDRA) version and summarized per system organ class (SOC) and preferred term (PT). | Up to 2 years | 
| Progression-Free Survival (PFS) | The time from first dose of MIRV until Investigator-assessed radiological progressive disease (PD) or death, whichever occurs first. | Up to 2 years | 
| Overall Survival (OS) | The time from first dose of MIRV until death. | Up to 2 years | 
| CA-125 Response | Serum CA-125 response determined using the Gynecologic Cancer Intergroup (GCIG) criteria. | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Platinum resistant, Folate-receptor alpha expression, Phase 3, Antibody-drug conjugate, mirvetuximab soravtansine, IMGN853, Epithelial Ovarian Cancer, Peritoneal Cancer, Fallopian Tube Cancer, MIRV, FRα