Clinical Trials /

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

NCT03832361

Description:

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).

Related Conditions:
  • Endometrial Adenocarcinoma
  • Endometrial Endometrioid Adenocarcinoma
  • Endometrial Serous Adenocarcinoma
  • Uterine Corpus Carcinosarcoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Evaluation of Mirvetuximab Soravtansine (IMGN853) in Women With Folate Receptor-α Positive Endometrial Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 2000023841
  • NCT ID: NCT03832361

Conditions

  • Endometrial Cancer

Interventions

DrugSynonymsArms
IMGN853mirvetuximab soravtansineIMGN853

Purpose

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).

Detailed 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.
    

Trial Arms

NameTypeDescriptionInterventions
IMGN853ExperimentalIMGN853 administered 6 mg/kg adjusted ideal body weight (AIBW) once every three weeks (Q3W)
  • IMGN853

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 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
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:5 Years
Safety Issue:
Description:Objective response rate (complete response and partial response rates) by RECIST 1.1 criteria of mirvetuximab soravtansine in patients with folate receptor α-positive persistent or recurrent endometrial cancer

Secondary Outcome Measures

Measure:Duration of overall survival (OS)
Time Frame:5 Years
Safety Issue:
Description:Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
Measure:Duration of progression free survival (PFS)
Time Frame:5 Years
Safety Issue:
Description:Progression-free survival is defined as the duration of time from study entry to time of progression, death, or the date of last contact, whichever occurs first.
Measure:Durable disease control rate (DDCR)
Time Frame:5 Years
Safety Issue:
Description:The percentage of patients who have achieved complete response, partial response, and stable disease.
Measure:Safety profile of mirvetuximab soravtansine (IMGN853) in endometrial cancer patients (adverse events as assessed by CTCAE v5.0)
Time Frame:5 Years
Safety Issue:
Description:Incidence of treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Alessandro Santin

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