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A Study of Mirvetuximab Soravtansine vs. Investigator's Choice of Chemotherapy in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression (MIRASOL)

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ClinicalTrials.gov Identifier: NCT04209855
Recruitment Status : Recruiting
First Posted : December 24, 2019
Last Update Posted : May 22, 2020
Sponsor:
Collaborator:
Gynecologic Oncology Group
Information provided by (Responsible Party):
ImmunoGen, Inc.

Study Description
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Brief Summary:
This Phase 3 study is designed to compare the efficacy and safety of mirvetuximab soravtansine vs. investigator's choice chemotherapy in patients with platinum-resistant high-grade epithelial ovarian cancer, primary peritoneal, or fallopian tube cancer, whose tumors express a high-level of FRα. Patients will be, in the opinion of the Investigator, appropriate for single-agent therapy for their next line of therapy. Folate receptor alpha (FRα) positivity will be defined by the Ventana FOLR1 (FOLR1-2.1) CDx assay.

Condition or disease Intervention/treatment Phase
Epithelial Ovarian Cancer Peritoneal Cancer Fallopian Tube Cancer Drug: Mirvetuximab Soravtansine Drug: Paclitaxel Drug: Topotecan Drug: Pegylated liposomal doxorubicin Phase 3

Detailed Description:
Patients will be randomized to either mirvetuximab soravtansine (MIRV) or Investigator's Choice chemotherapy (paclitaxel, PEGylated liposomal doxorubicin, or topotecan).
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 430 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: MIRASOL: A Randomized, Open-label, Phase 3 Study of Mirvetuximab Soravtansine vs. Investigator's Choice of Chemotherapy in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression
Actual Study Start Date : December 31, 2019
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: mirvetuximab soravtansine (MIRV; IMGN853)
MIRV 6 mg/kg adjusted ideal body weight (AIBW) every 3 weeks (Q3W)
 Drug: Mirvetuximab Soravtansine
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.
Other Names:
  • MIRV
  • IMGN853
Active Comparator: Investigator's choice of chemotherapy
  • Paclitaxel (Pac; 80 mg/m2) administered once per week (QW) within a 4-week cycle
  • Pegylated liposomal doxorubicin (PLD; 40 mg/m2) administered every 4 weeks (Q4W)
  • Topotecan (Topo; 4 mg/m2) administered either on Days 1, 8, and 15 every 4 weeks or for 5 consecutive days (1.25 mg/m2 Days 1-5) every 3 weeks (Q3W)
 Drug: Paclitaxel
Paclitaxel is a taxane that can stabilize microtubules to inhibit cell division. It was approved for treatment of recurrent epithelial ovarian cancer.

Drug: Topotecan
Topotecan induces irreversible DNA damage. It inhibits topoisomerase 1, leading to both single and double strand DNA break that eventually promote apoptosis. Topotecan was approved for treatment of epithelial ovarian cancer after failure of initial or subsequent chemotherapy.

Drug: Pegylated liposomal doxorubicin
Pegylated liposomal doxorubicin is a standard chemotherapy regimen used for treating platinum-resistant ovarian cancer. The active component doxorubicin is an anthracycline that intercalates DNA, leading to inhibition of replication and subsequently, the inhibition of proper cell division.


Outcome Measures
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Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Up to 2 years ]
    The time from date of randomization until Investigator-assessed progressive disease or death, whichever occurs first.


Secondary Outcome Measures :
  1. Safety and tolerability [ Time Frame: Up to 2 years ]
    Adverse events (AEs) will be evaluated according to the NCI CTCAE v5.0. AEs will be coded using the latest Medical Dictionary for Regulatory Activities (MedDRA) version and summarized per system organ class (SOC) and preferred term (PT).

  2. Objective Response Rate (ORR) [ Time Frame: Up to 2 years ]
    Objective response includes best response of complete response (CR) or partial response (PR).

  3. Overall survival [ Time Frame: Up to 2 years ]
    The time from date of randomization until the date of death

  4. Primary patient-reported outcomes [ Time Frame: Up to 2 years ]
    The number of patients achieving at least 15 point absolute improvement at Week 8 or Week 9 in the abdominal/GI scale of the European Organization for Research and Treatment of Cancer (EORTC) ovarian cancer specific quality of life questionnaire (QLQ-OV28). A higher score represents a better quality of life.

  5. Duration of response (DOR) [ Time Frame: Up to 2 years ]
    The time from initial response until Investigator-assessed progressive disease for all patients who achieve a confirmed objective response

  6. CA-125 response [ Time Frame: Up to 2 years ]
    Serum CA-125 response determined using the GCIG criteria

  7. Progression-free survival 2 (PFS 2) [ Time Frame: Up to 2 years ]
    The time from date of randomization until second disease progression or death whichever occurs first. Results will be summarized by arm


Other Outcome Measures:
  1. Patient-reported outcomes using EORTC QLQ-C30 questionnaires [ Time Frame: Up to 2 years ]
    The EORTC QLQ-C30 questionnaires will be used to collect data on the patient's functioning, health-related QOL, disease symptoms and health status. A higher score represents a higher response level.

  2. Patient-reported outcomes using EQ-5D-5L questionnaires [ Time Frame: Up to 2 years ]
    The EuroQol-5 Dimension 5-level (EQ-5D-5L) questionnaires will be used to collect data on the patient's functioning, health-related QOL, disease symptoms and health status. A higher score represents a higher response level.

  3. Pharmacokinetic parameters [ Time Frame: Up to 2 years ]
    Plasma samples will be collected to determine the concentration of MIRV (antibody-drug conjugate, total antibody, free DM4, S-methyl DM4 and possibly other metabolites). Summary statistics of the concentration at each time point (nominal time) will be presented. Graphical presentation of the data may also be completed using nominal time.

  4. Immunogenicity [ Time Frame: Up to 2 years ]
    The presence of anti-drug antibodies to mirvetuximab soravtansine

  5. Identification of soluble FRα levels and other biomarkers [ Time Frame: Up to 2 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Female patients ≥ 18 years of age
  2. Patients must have a confirmed diagnosis of high-grade serous epithelial ovarian cancer, 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 four 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
  4. Patients must have progressed on or after their most recent line of 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 IHC confirmation of FRα positivity
  6. Patient's tumor must be positive for FRα expression as defined by the Ventana FOLR1 (FOLR-2.1) CDx assay
  7. Patients must have at least one 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, and for whom single-agent therapy is appropriate as the next line of treatment:

    1. Adjuvant ± neoadjuvant considered one line of therapy
    2. Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered as part of the preceding line of therapy (ie, not counted independently)
    3. Therapy changed due to toxicity in the absence of progression will be considered as part of the same line (ie, not counted independently)
    4. Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance
  9. Patient must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1

  10. Time from prior therapy:

    1. Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is shorter)
    2. Focal radiation completed at least 2 weeks prior to first dose of study drug
  11. Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities
  12. Major surgery must be completed at least 4 weeks prior to first dose 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) (as defined in Section 5.9.6 in the protocol) while on study drug and for at least 3 months after the last dose of MIRV or at least 6 months after the last dose of paclitaxel, pegylated liposomal doxorubicin, or topotecan
  16. WCBP must have a negative pregnancy test within 4 days prior to the first dose of study drug

Exclusion Criteria:

  1. Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade or borderline ovarian tumor
  2. 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
  3. Patients with prior wide-field RT affecting at least 20% of the bone marrow
  4. Patients with > Grade 1 peripheral neuropathy per CTCAE v5.0
  5. 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

  6. 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. HIV infection
    3. Cytomegalovirus infection
    4. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks before starting study drug
  7. Patients with history of multiple sclerosis or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)

  8. Patients with clinically significant cardiac disease including, but not limited to, any one 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. Patients assigned to PLD stratum only: Left ventricular ejection fraction (LVEF) below the institutional limit of normal as measured by echocardiography (ECHO) or multigated acquisition (MUGA) scan
  10. Patients with a history of hemorrhagic or ischemic stroke within six months prior to randomization
  11. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)
  12. Patients with a previous clinical diagnosis of non-infectious interstitial lung disease (ILD), including noninfectious pneumonitis
  13. Patients with required use of folate-containing supplements (eg, folate deficiency)
  14. Patients with prior hypersensitivity to monoclonal antibodies
  15. Women who are pregnant or lactating
  16. Patients with 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 randomization. Note: does not include 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04209855


Contacts
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Contact: Elizabeth Noble 781-895-0176 Elizabeth.Noble@immunogen.com

Locations
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Sponsors and Collaborators
ImmunoGen, Inc.
Gynecologic Oncology Group
Investigators
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Study Director: Patrick A Zweidler-McKay, MD, PhD ImmunoGen, Inc.
More Information
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Responsible Party: ImmunoGen, Inc.
ClinicalTrials.gov Identifier: NCT04209855    
Other Study ID Numbers: IMGN853-0416
2019-003509-80 ( EudraCT Number )
First Posted: December 24, 2019    Key Record Dates
Last Update Posted: May 22, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ImmunoGen, Inc.:
Platinum-resistant
Folate-receptor alpha expression
Phase 3
Antibody-drug conjugate
mirvetuximab soravtansine
 IMGN853
Epithelial Ovarian Cancer
Peritoneal Cancer
Fallopian Tube Cancer
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
 Neoplasms by Histologic Type
Fallopian Tube Diseases
Paclitaxel
Maytansine
Doxorubicin
Liposomal doxorubicin
Topotecan
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors