Education and Training

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

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.

Stanford is currently accepting patients for this trial.

Intervention(s):

  • drug: Mirvetuximab soravtansine plus Bevacizumab
  • drug: Bevacizumab

Eligibility


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

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sanjana Karamcheti
skaram@stanford.edu
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