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

• ClinicalTrials.gov Identifier: NCT05445778
• Recruitment Status: Recruiting
• First Posted: July 6, 2022
• Last Update Posted: December 20, 2022
• Sponsor: ImmunoGen, Inc.
• Collaborator: GOG Foundation
• Information provided by (Responsible Party): ImmunoGen, Inc.

Study Description

Brief Summary:

GLORIOSA is a Phase 3 multicenter, open label study designed to evaluate the safety and efficacy of Mirvetuximab Soravtansine 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 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

• 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-positive Recurrent Platinum-sensitive Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancers Who Have Not Progressed After Second Line Platinum-based Chemotherapy Plus Bevacizumab
• Estimated Study Start Date: December 2022
• Estimated Primary Completion Date: March 2027
• Estimated Study Completion Date: April 2029

Arms and Interventions

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

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 ]
   Defined as patients who achieved a best overall response of CR or PR upon completion of triplet therapy
6. Assess DFS [ Time Frame: Up to 7 years ]
   Defined as 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 outcomes using EQ-5D-5L questionnaires [ Time Frame: Up to 7 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.
9. Patient-reported outcomes using the NCCN-FACT Ovarian Symptom Index (NFOSI-18) [ Time Frame: Up to 7 years ]
   A questionnaire assessing the health of patients with ovarian cancer.

Eligibility Criteria

• 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 ≥ 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 FRα positivity 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 at study entry (Pre-screening). 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. Patients with homologous recombination deficient-positive tumors who have received prior PARPi plus bevacizumab treatment are eligible.

6. Patients must have relapsed after 1 line (first line) of platinum-based chemotherapy and have platinum-sensitive disease 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 second line (recurrent platinum-sensitive, high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer)
8. Patients must have received no less than 4 and no more than 8 cycles of platinum-based triplet therapy in 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.
9. In the case of interval secondary cytoreductive surgery, patients are permitted to receive only 2 cycles of bevacizumab in combination with the last 3 cycles of platinum-based triplet therapy in the second line. In the case of primary cytoreductive surgery before second-line platinum-based triplet therapy, patients must have no less than 3 cycles of bevacizumab in combination with platinum-based chemotherapy after their surgery and before randomization.
10. Patients will either receive (per investigator's choice), must be receiving, or have received paclitaxel, gemcitabine, or PLD as the partner drug to platinum-based triplet therapy in the second line.
11. Patients must be in CR, PR, or SD, per the investigator, after completion of triplet therapy in second line to be eligible for randomization into the study population. All patients in both populations will have computed tomography (CT)/magnetic resonance imaging (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 triplet therapy in 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 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 either have 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 maintenance treatment and have recovered or stabilized from the side effects of prior surgery before the first dose of maintenance 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 Note: For Run-In patients, these criteria must be met before initiation of triplet therapy and before start of maintenance therapy.
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 maintenance 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. 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. Patients with PD while on or following platinum-based triplet therapy
4. 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. 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 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, gastrointestinal perforation, or intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic examination, bowel involvement on CT scan, or clinical symptoms of bowel obstruction
16. Clinically significant proteinuria: urine-protein (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 24-hour period.
17. History of Grade 4 thromboembolic events
18. Patients requiring use of folate-containing supplements (eg, folate deficiency)
19. Patients with prior hypersensitivity to monoclonal antibodies (mAbs)
20. Women who are pregnant or breastfeeding
21. Patients who received prior treatment with MIRV or other FRα-targeting agents
22. Patients with untreated or symptomatic central nervous system metastases
23. Patients with a history of other malignancy within 3 years before enrollment 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.
24. Prior known hypersensitivity reactions to study drugs or any of their excipients

Contacts and Locations

Contacts

Contact: ImmunoGen, Inc.; 781-895-0600; medicalaffairs@immunogen.com

Locations

United States, Louisiana

LSUHSC; Not yet recruiting

New Orleans, Louisiana, United States, 70112

Contact: Maria Stambaugh 504-210-1846

Principal Investigator: Amelia Jernigan, MD

United States, Nevada

Center of Hope at Renown Medical Center; Recruiting

Reno, Nevada, United States, 89511

Contact: Shannon Pierpoint 775-327-4673

Principal Investigator: Peter Lim

United States, New York

Womens Cancer Care Associates; Recruiting

Albany, New York, United States, 12208

Contact: NICOLINA SURIANO 518-458-1390 NSURIANO@WOMENSCANCERCAREASSOCIATES.COM

Principal Investigator: JOYCE BARLIN

United States, North Carolina

Duke Cancer Center; Not yet recruiting

Durham, North Carolina, United States, 27710

Contact: Jennifer Mewshaw 919-684-3780 jennifer.mewshaw@duke.edu

Principal Investigator: Angeles Secord

Sponsors and Collaborators

ImmunoGen, Inc.

GOG Foundation

More Information

• Responsible Party: ImmunoGen, Inc.
• ClinicalTrials.gov Identifier: NCT05445778
• Other Study ID Numbers: IMGN853-0421
• First Posted: July 6, 2022
• Last Update Posted: December 20, 2022
• Last Verified: September 2022

• 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:

Fallopian Tube Neoplasms; Peritoneal Neoplasms; Hypersensitivity; Neoplasms by Site; Neoplasms; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Fallopian Tube Diseases; Immune System Diseases; Abdominal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Bevacizumab; Maytansine; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents, Phytogenic; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action