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

• Status: Recruiting
• Trial end date: 2023-09-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ImmunoGen, Inc.
• Collaborators: European Network of Gynaecological Oncological Trial Groupbs; Gynecologic Oncology Group
• Treatments: Albumin-Bound Paclitaxel; Doxorubicin; Folic Acid; Immunoconjugates; Liposomal doxorubicin; Maytansine; Paclitaxel; Topotecan; Vitamin B Complex

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