Evaluating a new treatment for women with specific types of endometrial cancer

A Phase II Evaluation of the Safety and Efficacy of Mirvetuximab Soravtansine (IMGN853) in Women With Folate Receptor-α Positive Persistent or Recurrent Endometrial Cancer

This study is testing a new treatment called mirvetuximab soravtansine to see if it can help women with certain types of endometrial cancer feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 100 Years
• Sex: Female
• Sponsor: Yale University (Academic / other)
• Drugs / interventions: chemotherapy, radiation, mirvetuximab
• Locations: 1 site (New Haven, Connecticut)
• Trial ID: NCT03832361 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the effectiveness and safety of mirvetuximab soravtansine (IMGN853) in women diagnosed with type II endometrial cancers that express folate receptor alpha (FRα). Participants will include those with persistent or recurrent uterine serous carcinoma, Grade 3 endometrial adenocarcinoma, or carcinosarcoma with high-grade components. The study will measure the objective response rate (ORR) as the primary outcome, while secondary outcomes will include overall survival (OS), progression-free survival (PFS), and safety assessments. Patients will receive IMGN853 intravenously every three weeks until disease progression or unacceptable toxicity occurs.

Who should consider this trial

Good fit: Ideal candidates for this study are women with persistent or recurrent FRα-positive endometrial cancer who have measurable disease and have received up to three prior lines of therapy.

Not a fit: Patients with endometrial cancer that does not express folate receptor alpha or those who have received prior folate receptor-targeting therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for women with FRα-positive endometrial cancer, potentially improving their response rates and survival outcomes.

How similar studies have performed: While this specific approach is novel, similar studies targeting folate receptor alpha in other cancers have shown promising results.

Eligibility criteria

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

Where this trial is running

New Haven, Connecticut

• Smilow Cancer Hospital at Yale New Haven — New Haven, Connecticut, United States (Recruiting)

Study contacts

• Principal investigator: Alessandro D. Santin, M.D. — Yale University
• Study coordinator: Alessandro D. Santin, M.D.

Conditions Endometrial Cancer