SORAYA: A Phase 3, Single Arm Study of Mirvetuximab Soravtansine in Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers with High Folate Receptor-Alpha Expression

This study is designed to evaluate the efficacy and safety of mirvetuximab soravtansine
(MIRV) in patients with platinum-resistant high-grade serous epithelial ovarian cancer,
primary peritoneal, or fallopian tube cancer, whose tumors express a high-level of Folate
Receptor-Alpha (FRα). Patients will be, in the opinion of the Investigator, appropriate for
single-agent therapy for their next line of therapy. All patients will receive single-agent
MIRV at 6 mg/kg adjusted ideal body weight administered on Day 1 of every 3-week cycle.

Inclusion Criteria:

1. Female patients ≥ 18 years of age

2. Patients must have a confirmed diagnosis of high-grade serous epithelial ovarian
cancer (EOC), primary peritoneal cancer, or fallopian tube cancer

3. Patients must have platinum-resistant disease:

1. Patients who have only had 1 line of platinum based therapy must have received at
least 4 cycles of platinum, must have had a response (complete response/remission
(CR) or partial response/remission (PR)) and then progressed between > 3 months
and ≤ 6 months after the date of the last dose of platinum

2. Patients who have received 2 or 3 lines of platinum therapy must have progressed
on or within 6 months after the date of the last dose of platinum

Note: Progression should be calculated from the date of the last administered dose of
platinum therapy to the date of the radiographic imaging showing progression

Note: Patients who are platinum refractory during front-line treatment are excluded
(see exclusion criteria)

4. Patients must have progressed radiographically on or after their most recent line of
anticancer therapy.

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 immunohistochemistry (IHC) confirmation of Folate Receptor α (FRα) positivity

6. Patient's tumor must be positive for FRα expression as defined by the Ventana FOLR1
Assay

7. Patients must have at least 1 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, including at least 1 line of therapy containing bevacizumab, and
for whom single-agent therapy is appropriate as the next line of treatment:

1. Adjuvant ± neoadjuvant considered 1 line of therapy

2. Maintenance therapy (e.g., bevacizumab, poly adenosine diphosphate-ribose
polymerase (PARP) inhibitors) will be considered part of the preceding line of
therapy (i.e., not counted independently)

3. Therapy changed due to toxicity in the absence of progression will be considered
part of the same line (i.e., not counted independently)

4. Hormonal therapy will be counted as a separate line of therapy unless it was
given as maintenance

9. Patients must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS)
of 0 or 1

10. Patients must have completed prior therapy within the specified times below:

1. Systemic antineoplastic therapy within 5 half-lives or 4 weeks (whichever is
shorter) prior to first dose of MIRV

2. Focal radiation completed at least 2 weeks prior to first dose of MIRV

11. Patients must have stabilized or recovered (Grade 1 or baseline) from all prior
therapy-related toxicities (except alopecia)

12. Patients must have completed any major surgery at least 4 weeks prior to first dose of
MIRV 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 10^9/L (1,500/μL) without G-CSF in the
prior 10 days or long-acting WBC growth factors in the prior 20 days

2. Platelet count ≥ 100 x 10^9/L (100,000/μL) without platelet transfusion in the
prior 10 days

3. Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the
prior 21 days

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 5.8.6 of the protocol) while on MIRV
and for at least 3 months after the last dose

16. WCBP must have a negative pregnancy test within the 4 days prior to the first dose of
MIRV

Exclusion Criteria:

1. Male patients

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

3. Patients with primary platinum-refractory disease, defined as disease that did not
respond to (CR or PR) or has progressed within 3 months of the last dose of first-line
platinum-containing chemotherapy

4. Patients with prior wide-field radiotherapy (RT) affecting at least 20 percent of the
bone marrow

5. Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria for
Adverse Events (CTCAE)

6. 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

7. 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. Human immunodeficiency virus (HIV) infection

3. Active cytomegalovirus infection

4. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks
prior to the first dose of MIRV

Note: Testing at screening is not required for the above infections unless clinically
indicated

8. Patients with a history of multiple sclerosis (MS) or other demyelinating disease
and/or Lambert-Eaton syndrome (paraneoplastic syndrome)

9. Patients with clinically significant cardiac disease including, but not limited to,
any 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

10. Patients with a history of hemorrhagic or ischemic stroke within 6 months prior to
enrollment

11. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)

12. Patients with a previous clinical diagnosis of noninfectious interstitial lung disease
(ILD), including noninfectious pneumonitis

13. Patients requiring use of folate-containing supplements (eg, folate deficiency)

14. Patients with prior hypersensitivity to monoclonal antibodies (mAb)

15. Women who are pregnant or breastfeeding

16. Patients who received 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 enrollment.

Note: patients with 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) are eligible

19. Prior known hypersensitivity reactions to study drugs and/or any of their excipients