Evaluation of Mirvetuximab Soravtansine (IMGN853) in Women With Folate Receptor-α Positive Endometrial Cancer

This study will enroll patients with persistent or recurrent FRα-positive uterine serous
carcinoma (pure or mixed), Grade 3 endometrial adenocarcinoma, or carcinosarcoma with high
grade serous or Grade 3 endometrioid components. All patients must have measurable disease.
The primary objective of the study is to assess the activity of IMGN853 as measured by
objective response rate (ORR). The secondary objectives are to assess the duration of overall
survival (OS), progression-free survival (PFS) and durable disease control rate (DDCR), as
well as the safety profile of IMGN853 in endometrial carcinoma patients.
Exploratory/correlative objectives are to correlate ORR, PFS, and OS with the level of folate
receptor α expression and explore use of circulating tumor (ct) DNA as a biomarker for
disease response and compare its performance to cancer antigen 125 (CA-125). All enrolled
patients will receive IMGN853 at a dose of 6 mg/kg administered intravenously once every 3
weeks until unacceptable toxicity or progression of disease requiring discontinuation of
treatment.

Inclusion Criteria:

- Radiologically confirmed (ie, CT scan and/or MRI) persistent or recurrent endometrial
cancer

- Patients must have one of the following pathologically documented, definitively
diagnosed tumor types: Uterine serous carcinoma (Pure or Mixed), Grade 3 endometrial
adenocarcinoma, or Carcinosarcoma with high grade serous or Grade 3 endometrioid
components

- Have measurable disease

- FRα-positive tumor expression as defined in the protocol

- Have at least one "target lesion" to be used to assess response as defined by RECIST
v1.1

- Patients must have received prior treatment with ≤ 2 prior lines of therapy for
recurrent disease; hormonal agents are not considered a line of therapy; prior
treatment with folate receptor-targeting investigational agents is not allowed

- Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Time from prior therapy: Systemic anti-neoplastic therapy: five half-lives or four
weeks, whichever is shorter; Radiotherapy: wide-field radiotherapy completed at least
four weeks, or focal radiation completed at least two weeks, prior to starting study
treatment

- Patients must have resolution of toxic effect(s) of the most recent prior chemotherapy

- Patients must have adequate hematologic, liver and kidney function as defined in the
protocol

- Women of child bearing potential (WCBP), must agree to use effective contraceptive
methods during study treatment and for at least twelve weeks after the last dose of
IMGN853

- WCBP must have a negative pregnancy test within 3 days prior to the first dose of
study treatment

- At time of initial surgery, patient may have either been optimally or suboptimally
debulked

- Have signed the informed consent form, and willing to adhere to the study visit
schedule and other protocol requirements

- ≥ 18 years of age

Exclusion Criteria:

- Active or chronic corneal disorder

- Serious concurrent illness or clinically-relevant active infection as defined in the
protocol

- Clinically-significant cardiac disease such as recent myocardial infarction (≤ 6
months prior to day 1), unstable angina pectoris, uncontrolled congestive heart
failure, uncontrolled hypertension, prior history of hypertensive crisis or
hypertensive encephalopathy, uncontrolled cardiac arrhythmias, clinically-significant
vascular disease, severe aortic stenosis, clinically significant peripheral vascular
disease, or cardiac toxicity following prior chemotherapy

- History of neurological conditions

- History of hemorrhagic or ischemic stroke within the last 6 months

- History of cirrhotic liver disease

- Previous clinical diagnosis of non-infectious pneumonitis

- Prior hypersensitivity to monoclonal antibodies

- Women who are pregnant or breast feeding

- Carcinomatous meningitis, untreated central nervous system (CNS) disease or
symptomatic CNS metastasis

- History or evidence of thrombotic or hemorrhagic disorders within 6 months before
first study treatment

- Required used of folate-containing supplements (e.g. folate deficiency)

- Has a known additional malignancy that is progressing or required active treatment
within 3 years of first dose of study treatment