Clinical Trials /

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

NCT04296890

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • High Grade Ovarian Serous Adenocarcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: IMGN853-0417
  • SECONDARY ID: 2020-000179-19
  • NCT ID: NCT04296890

Conditions

  • Epithelial Ovarian Cancer
  • Peritoneal Cancer
  • Fallopian Tube Cancer

Interventions

DrugSynonymsArms
Mirvetuximab SoravtansineIMGN853, MIRVTreatment

Purpose

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

      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±1 weeks from Cycle 1 Day 1 (C1D1) for the first 36 weeks
      then every 12±3 weeks until disease progression, death, or the start of new anticancer
      therapy (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 (± 1 week). 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±1 months 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.
    

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalAll 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).
  • Mirvetuximab Soravtansine

Eligibility Criteria

        Inclusion Criteria:

          1. Females patients ≥ 18 years of age

          2. Patients must have a confirmed diagnosis of high-grade serous epithelial ovarian
             cancer (EOC), primary peritoneal cancer, or fallopian tube cancer

          3. Patients must have platinum-resistant disease (defined as progression within 6 months
             from completion of a minimum of 4 cycles of platinum-containing therapy).

             Note: This should be calculated from the date of the last administered dose of
             platinum therapy to the date of the radiographic imaging showing progression; patients
             who are platinum refractory during front-line treatment are excluded (see exclusion
             criteria)

          4. Patients must have progressed on or after their most recent line of anticancer
             therapy.

             Note: Progression must be determined radiographically and/or by CA-125 GCIG
             progression criteria

          5. 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

          6. Patient's tumor must be positive for FRα expression as defined by the Ventana FOLR1
             Assay

          7. Patients must have at least 1 lesion that meets the definition of measurable disease
             by RECIST v1.1 (radiologically measured by the Investigator)

          8. 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:

               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. Patients must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS)
             of 0 or 1

         10. Patients 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. Patients must have stabilized or recovered (Grade 1 or baseline) from all prior
             therapy-related toxicities (except alopecia)

         12. 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

         13. Patients must have adequate hematologic, liver and kidney functions defined as:

               1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1,500/μL)

               2. Platelet count ≥ 100 x 109/L (100,000/μL) without platelet transfusion in the
                  prior 10 days

               3. Hemoglobin ≥ 9.0 g/dL

               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. 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

         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 patients

          2. Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed
             tumors containing any of the above histologies, or low-grade/borderline ovarian tumor

          3. Patients with primary platinum-refractory disease, defined as disease that did not
             respond to or has progressed within 3 months of the last dose of first-line
             platinum-containing chemotherapy

          4. Patients with prior wide-field radiotherapy (RT) affecting at least 20 percent of the
             bone marrow

          5. Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria for
             Adverse Events (CTCAE)

          6. 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

          7. Patients 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. Cytomegalovirus infection

               4. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks
                  prior to the first dose of MIRV

          8. Patients with a history of multiple sclerosis (MS) or other demyelinating disease
             and/or Lambert-Eaton syndrome (paraneoplastic syndrome)

          9. Patients 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. Patients with a history of hemorrhagic or ischemic stroke within 6 months prior to
             enrollment

         11. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)

         12. Patients with a previous clinical diagnosis of noninfectious interstitial lung disease
             (ILD), including noninfectious pneumonitis

         13. Patients requiring use of folate-containing supplements (eg, folate deficiency)

         14. Patients with prior hypersensitivity to monoclonal antibodies (mAb)

         15. Women who are pregnant or breastfeeding

         16. Patients who received prior treatment with MIRV or other FRα-targeting agents

         17. Patients with untreated or symptomatic central nervous system (CNS) metastases

         18. 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:Duration of Response (DOR)
Time Frame:Up to 2 years
Safety Issue:
Description:The time from initial Investigator-assessed response (CR or PR) until progressive disease (PD) as assessed by the Investigator
Measure:Adverse Events (AEs)
Time Frame:Up to 2 years
Safety Issue:
Description: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).
Measure:Progression-Free Survival (PFS)
Time Frame:Up to 2 years
Safety Issue:
Description:The time from first dose of MIRV until Investigator-assessed radiological progressive disease (PD) or death, whichever occurs first.
Measure:Overall Survival (OS)
Time Frame:Up to 2 years
Safety Issue:
Description:The time from first dose of MIRV until death.
Measure:CA-125 Response
Time Frame:Up to 2 years
Safety Issue:
Description:Serum CA-125 response determined using the Gynecologic Cancer Intergroup (GCIG) criteria.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ImmunoGen, Inc.

Trial Keywords

  • Platinum resistant
  • Folate-receptor alpha expression
  • Phase 3
  • Antibody-drug conjugate
  • mirvetuximab soravtansine
  • IMGN853
  • Epithelial Ovarian Cancer
  • Peritoneal Cancer
  • Fallopian Tube Cancer
  • MIRV
  • FRα

Last Updated

April 2, 2020