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

Alessandro Santin

Status and phase

Enrolling

Phase 2

Conditions

Endometrial Cancer

Treatments

Drug: IMGN853

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT03832361

2000023841

Details and patient eligibility

About

The purpose of this study is to evaluate the activity and safety profile of mirvetuximab soravtansine (IMGN853) in patients with type II endometrial cancers that overexpress folate receptor alpha (FRα).

Full description

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.

Enrollment

50 estimated patients

Sex

Female

Ages

18 to 100 years old

Volunteers

No Healthy Volunteers

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 2 or Grade 3 endometrial adenocarcinoma, Carcinosarcoma with high grade serous or Grade 2/3 endometrioid components, or clear cell carcinoma (Pure or Mixed).
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 ≤ 3 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 4 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