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Mirvetuximab Soravtansine With Bevacizumab Versus Bevacizumab as Maintenance in Platinum-sensitive Ovarian, Fallopian Tube, or Peritoneal Cancer (GLORIOSA)

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ClinicalTrials.gov Identifier: NCT05445778
Recruitment Status : Recruiting
First Posted : July 6, 2022
Last Update Posted : March 29, 2024
Sponsor:
Collaborator:
GOG Foundation
Information provided by (Responsible Party):
ImmunoGen, Inc.

Study Description
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Brief Summary:
GLORIOSA is a Phase 3 multicenter, open label study designed to evaluate the safety and efficacy of mirvetuximab Soravtansine as maintenance therapy in participants with platinum-sensitive ovarian, primary peritoneal or fallopian tube cancers with high folate receptor-alpha (FRα) expression.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Peritoneal Cancer Fallopian Tube Cancer Drug: Mirvetuximab soravtansine plus Bevacizumab Drug: Bevacizumab Phase 3

Detailed Description:

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 folate receptor alpha (FRα). It is being developed as maintenance therapy for the treatment of subjects with recurrent platinum-sensitive, highgrade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression. Patients must have confirmation of FRα positivity by the Ventana FOLR1 Assay.

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 418 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized, Multicenter, Open-label, Phase 3 Study of Mirvetuximab Soravtansine in Combination With Bevacizumab Versus Bevacizumab Alone as Maintenance Therapy for Patients With FRα-high Recurrent Platinum-sensitive Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancers Who Have Not Progressed After Second Line Platinum-based Chemotherapy Plus Bevacizumab (GLORIOSA)
Actual Study Start Date : December 27, 2022
Estimated Primary Completion Date : March 2027
Estimated Study Completion Date : April 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Allergy
Drug Information available for: Bevacizumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm 1
Mirvetuximab Soravtansine (MIRV) plus Bevacizumab
 Drug: Mirvetuximab soravtansine plus Bevacizumab
Participants will receive MIRV 6.0 mg/kg adjusted ideal body weight (AIBW) plus Bevacizumab 15mg/kg every 3 weeks
Other Name: MIRV
Active Comparator: Arm 2
Bevacizumab monotherapy
 Drug: Bevacizumab
Participants will receive Bevacizumab 15mg/kg every 3 weeks


Outcome Measures
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Primary Outcome Measures :
  1. Assess Progression-free survival (PFS) [ Time Frame: Up to 4 years ]
    Progression-free survival defined as the time from date of randomization until investigator-assessed progressive disease (PD) or death, whichever occurs first.


Secondary Outcome Measures :
  1. Assess Overall survival (OS) [ Time Frame: Up to 7 years ]
    Overall survival (OS), defined as the time from randomization to death

  2. Assess Safety and tolerability [ Time Frame: Up to 7 years ]
    Adverse events (AEs) will be evaluated according to the NCI CTCAE v5.0

  3. Assess second disease progression (PFS2) [ Time Frame: Up to 7 years ]
    Second disease progression (PFS2)defined as the time from date of randomization until second disease progression or death, whichever occurs first

  4. Assess Objective Response Rate (ORR) [ Time Frame: Up to 7 years ]
    Objective response includes best response of complete response (CR) or partial response (PR).

  5. Assess Duration of response (DOR) [ Time Frame: Up to 7 years ]
    Measured only in patients who achieved a confirmed best overall response of CR or PR upon completion of platinum-based combination chemotherapy with bevacizumab (triplet therapy)

  6. Assess Disease-free survival (DFS) [ Time Frame: Up to 7 years ]
    Measured only in patients who have no measurable disease per RECIST v1.1 at randomization

  7. CA-125 response [ Time Frame: Up to 7 years ]
    Serum CA-125 response determined using the GCIG criteria

  8. Patient-reported outcome health-related quality of life (HRQoL) of disease-related symptoms using the NCCN-FACT Ovarian Symptom Index (NFOSI-18) DRS-P (disease-related symptom subscale - physical). [ Time Frame: Up to 7 years ]
    A questionnaire assessing the health of patients with ovarian cancer.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must be ≥ 18 years of age
  2. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  3. Patients must have a confirmed diagnosis of high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer.
  4. Patients must be willing to provide an archival tumor tissue block or slides, or must undergo a procedure to obtain a new biopsy using a low-risk, medically routine procedure for IHC confirmation of high FRα expression (reported as "positive") as defined by the Ventana FOLR1 Assay. Patients must be confirmed FRα-high as defined by FRα positivity of ≥ 75% of tumor membrane staining at ≥ 2+ intensity (PS2+) for entry into the study.

  5. Prior BRCA testing on the tumor or prior germline testing is required for eligibility. If not done prior, tumor or germline testing will need to be done before study entry. Somatic and germline BRCA-positive patients must have received prior treatment with a PARPi in maintenance following first-line treatment.

    Note: Local tumor or germline BRCA testing will be acceptable for stratification. If the patient has not been tested, recommend archival tumor samples to be assessed for tissue BRCA. All patients who have received prior first line PARPi maintenance and/or bevacizumab are eligible.

  6. Patients' disease must have relapsed after 1 line (first line) of platinum-based chemotherapy and must be platinum-sensitive defined as progression greater than 6 months from last dose of primary platinum therapy.
  7. Patients must be appropriate for, currently be on, or have completed platinum-based triplet therapy in the second line (recurrent PSOC).

  8. After completion of triplet therapy and before randomization, patients must have received no less than 4 and no greater than 8 cycles of platinum-based triplet therapy in the second line, to include no less than 3 cycles of bevacizumab in combination with platinum-based chemotherapy. If the number of cycles received is less than 6 due to toxicity, this must be documented and toxicity assessed as unlikely related to bevacizumab.

    Note: A minimum of 4 cycles of combination chemotherapy is required. If carboplatin, paclitaxel, gemcitabine, or pegylated liposomal doxorubicin (PLD) is stopped due to toxicity, up to 4 additional cycles of single agent in combination with bevacizumab is acceptable if appropriately documented.

  9. After completion of triplet therapy and before randomization: In the case of interval secondary cytoreductive surgery, patients are permitted to have received only 2 cycles of bevacizumab if given in combination with the last 3 cycles of platinum-based triplet therapy in the second line. In the case of primary cytoreductive surgery before secondline platinum-based triplet therapy, patients must have received no fewer than 3 cycles of bevacizumab in combination with platinum-based chemotherapy after their surgery and before randomization.
  10. Patients either will receive (per investigator's choice), must be receiving, or have received paclitaxel, gemcitabine, or pegylated liposomal doxorubicin as the partner drug to platinum-based triplet therapy in the second line.
  11. After completion of triplet therapy and before randomization, patients must have achieved a CR, PR, or SD, per the investigator, in the second line to be eligible for randomization into the study population. All patients will have CT or MRI scans and CA-125 measurements at least 3 weeks but no more than 8 weeks after their last planned dose of triplet therapy and before randomization.
  12. Patients must be randomized no later than 8 weeks from the last dose of platinum-based triplet therapy in the second line.

  13. After completion of triplet therapy and before randomization, patients must meet one of the following criteria:

    1. Have at least 1 lesion that meets the definition of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (radiologically measured by the investigator), and determined by the investigator to either have SD or a PR to their treatment; or
    2. Have persistently elevated CA-125 without measurable disease and determined by the investigator to have either SD or a PR to their treatment; or
    3. Have clinically no evidence of disease by both radiographic interpretation by the investigator and normalization of their CA-125, determined to be a CR.
  14. Patients must have stabilized or recovered (to Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia).
  15. Patients must have completed any major surgery at least 4 weeks before the first dose of study treatment (either Run-In or maintenance therapy) and have recovered or stabilized from the side effects of prior surgery before the first dose of treatment on study.

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

    1. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/μL) without granulocyte colony-stimulating factor in the prior 10 days or long-acting white blood cell (WBC) growth factors in the prior 10 days of C1D1 of maintenance treatment.
    2. Platelet count ≥ 100 × 109/L (100,000/μL) without platelet transfusion in the prior 10 days of C1D1 of maintenance treatment
    3. Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 10 days of C1D1 of maintenance treatment
    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 (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 × ULN)
    7. Serum albumin ≥ 2 g/dL
  17. Patients must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements.
  18. Females of childbearing potential (FCBP) must agree to use highly effective contraceptive method(s) (as defined in Section 5.10.7) while on study medication and for at least 3 months after the last dose.
  19. FCBP must have a negative pregnancy test within 4 days before the first dose of therapy.

Exclusion Criteria:

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

  2. More than one line of prior chemotherapy before current/planned triplet therapy. 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. Change due to toxicity will be considered part of the proceeding line of therapy.
  3. Patients with PD while on or following platinum-based triplet therapy
  4. After completion of triplet therapy and prior to randomization: Patients who receive an intervening dose of bevacizumab after the last dose of triplet therapy before randomization
  5. Patients with prior wide-field radiotherapy affecting at least 20% of the bone marrow
  6. Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE)
  7. 7. 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

  8. 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. Active cytomegalovirus infection
    4. Any other concurrent infectious disease requiring intravenous (IV) antibiotics within 2 weeks before the first dose of maintenance therapy Note: Testing at screening is not required for the above infections unless clinically indicated.
  9. Patients with a history of multiple sclerosis or other demyelinating diseases and/or Lambert-Eaton syndrome (paraneoplastic syndrome)

  10. Patients with clinically significant cardiac disease including, but not limited to, any of the following:

    1. Myocardial infarction ≤ 6 months prior to C1D1 of maintenance treatment
    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
  11. Patients with a history of hemorrhagic or ischemic stroke within 6 months before enrollment
  12. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)
  13. Patients 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)
  14. History of bowel obstruction (including sub-occlusive disease) related to underlying disease within 6 months before the start of maintenance study treatment (triplet therapy for Run-In patients).
  15. History of abdominal fistula or gastrointestinal perforation
  16. Intra-abdominal abscess, evidence of rectosigmoid involvement by pelvic examination, bowel involvement on CT scan, or clinical symptoms of bowel obstruction within 4 weeks prior to randomization (or within 4 weeks prior to starting triplet therapy for Run- In patients)
  17. Clinically significant proteinuria: urine-protein to creatinine (UPC) ratio ≥ 1.0 or urine dipstick result ≥ 2+; patients with UPC ratio ≥ 1.0 or ≥ 2+ proteinuria should undergo 24-hour urine collection and must show result ≤ 1 g of protein in a 24-hour period.
  18. History of Grade 4 thromboembolic events
  19. Patients not appropriate for bevacizumab 15 mg/kg dosing at the start of maintenance therapy as per the treating physician
  20. Patients requiring use of folate-containing supplements (eg, folate deficiency)
  21. Patients with prior hypersensitivity to monoclonal antibodies (mAbs)
  22. Women who are pregnant or breastfeeding
  23. Patients who received prior treatment with MIRV or other FRα-targeting agents
  24. Patients with untreated or symptomatic central nervous system metastases

  25. Patients with a history of other malignancy within 3 years prior to signing study consent

    Note: Patients with tumors with a negligible risk for metastasis or death (eg, controlled basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast) are eligible.

  26. Prior known hypersensitivity reactions to study drugs or any of their excipients
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): NCT05445778


Contacts
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Contact: ImmunoGen, Inc. 781-895-0600 medicalinformation@immunogen.com

Locations
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Sponsors and Collaborators
ImmunoGen, Inc.
GOG Foundation
More Information
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Responsible Party: ImmunoGen, Inc.
ClinicalTrials.gov Identifier: NCT05445778    
Other Study ID Numbers: IMGN853-0421
First Posted: July 6, 2022    Key Record Dates
Last Update Posted: March 29, 2024
Last Verified: March 2024

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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-sensitive
Folate-receptor alpha expression
Antibody-drug conjugate
Cancer
Ovarian Neoplasma
Recurrent Platinum-Sensitive
 High-Grade Ovarian
ADC
Adult
AYA
Adolescent Young Adult
Additional relevant MeSH terms:
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Fallopian Tube Neoplasms
Peritoneal Neoplasms
Hypersensitivity
Neoplasms by Site
Neoplasms
Adnexal Diseases
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Genital Diseases
Immune System Diseases
Fallopian Tube Diseases
 Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Bevacizumab
Maytansine
Mirvetuximab soravtansine
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents, Phytogenic