Clinical Trials /

Mirvetuximab Soravtansine in Localized Triple-Negative Breast Cancer (TNBC)

NCT03106077

Description:

The goal of this clinical research study is to learn if mirvetuximab soravtansine can help to control either newly diagnosed or metastatic (has spread) triple-negative breast cancer (TNBC). Mirvetuximab soravtansine is designed to stop cell growth by blocking certain proteins in the cancer cells related to the mineral folate. This is believed to cause the cancer cells to die.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Mirvetuximab Soravtansine in Localized Triple-Negative Breast Cancer (TNBC)
  • Official Title: Women's Triple-Negative First-Line Study: A Phase II Trial of Mirvetuximab Soravtansine in Patients With Localized Triple-Negative Breast Cancer (TNBC) With Tumors Predicted Insensitive to Standard Neoadjuvant Chemotherapy (NACT), Including a Lead-in Cohort to Establish Activity in Patients With Metastatic TNBC

Clinical Trial IDs

  • ORG STUDY ID: 2016-0683
  • NCT ID: NCT03106077

Conditions

  • Malignant Neoplasm of Breast

Interventions

DrugSynonymsArms
Mirvetuximab SoravtansineIMGN853Metastatic Triple-Negative Breast Cancer (TNBC)

Purpose

The goal of this clinical research study is to learn if mirvetuximab soravtansine can help to control either newly diagnosed or metastatic (has spread) triple-negative breast cancer (TNBC).

Mirvetuximab soravtansine is designed to stop cell growth by blocking certain proteins in the cancer cells related to the mineral folate. This is believed to cause the cancer cells to die.

Detailed Description

There are 2 cohorts in this study. If you have metastatic TNBC, you will be in Cohort A. If you have newly diagnosed TNBC, you will be in Cohort B.

Study Drug Administration:

On Day 1 of each 21-day cycle, you will receive mirvetuximab soravtansine by vein over about 2-3 hours. If you cannot tolerate the study drug, your dose may be lowered or stopped.

Length of Study:

If you are in Cohort A, you may receive mirvetuximab soravtansine for as long as the study doctor thinks it is in your best interest. If you are in Cohort B, you may receive mirvetuximab soravtansine for up to 4 cycles. After 4 cycles, you will have surgery as part of your standard care.

You will no longer be able to receive the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Study Visits:

On Day 1 of each cycle:

- You will have a physical exam.

- Blood (about 2 tablespoons) will be drawn for routine tests.

- If you can become pregnant, part of the above routine blood sample or urine will be collected for a pregnancy test.

You will come back to the clinic on Day 2 of Cycles 1-3. At these visits, your vital signs will be collected and the study doctor or study staff will check on your health.

On Days 8 and 15 of Cycles 1-3, blood (about 2 tablespoons) will be drawn for routine tests.

During even-numbered cycles (Cycles 2, 4, 6, and so on):

- You will have imaging scans. The study doctor will tell you what type of scans you will have.

- If the doctor thinks it is needed, you will have an eye exam.

End-of-Treatment Visit:

As soon as possible after your last cycle of study drug:

- You will have a physical exam.

- Blood (about 2 tablespoons) will be drawn for routine tests

- If the doctor thinks it is needed, you will have an eye exam.

- You will have imaging scans.

- If you are in Cohort B, you will have a core tumor biopsy to check the status of the disease.

If you are in Cohort B, you will have surgery as part of your standard treatment.

Follow-Up:

Within 30 days after your last dose of study drug:

- You will have a physical exam.

- Blood (about 2 tablespoons) will be drawn for routine tests.

- If you did not have them performed at the end-of-treatment visit, you will have imaging scans.

- If you can become pregnant, part of the above routine blood sample or urine will be collected for a pregnancy test.

You will continue to have imaging scans every 12 weeks for up to 1 year after your first dose of study drug. If the disease gets worse or you start a new anti-cancer therapy, these scans will stop.

This is an investigational study. Mirvetuximab soravtansine is not FDA approved or commercially available. It is currently being used for research purposes only.

The study doctor can explain more and answer questions for how the study drug is designed to work.

Up to 57 participants will be enrolled in this study. All will take part at MD Anderson.

Trial Arms

NameTypeDescriptionInterventions
Metastatic Triple-Negative Breast Cancer (TNBC)ExperimentalParticipants receive Mirvetuximab Soravtansine once every 3 weeks. Participants treated until disease progression, therapy intolerance or withdrawal of informed consent.
  • Mirvetuximab Soravtansine
Newly Diagnosed Triple-Negative Breast Cancer (TNBC)ExperimentalParticipants receive Mirvetuximab Soravtansine once every 3 weeks. Participants receive a maximum of 4 cycles of therapy prior to undergoing surgical resection. Patients allowed to discontinue therapy for intolerance, disease progression or withdrawal of consent.
  • Mirvetuximab Soravtansine
Metastatic Run-In CohortExperimental14 participants recruited in the first stage to receive Mirvetuximab Soravtansine once every 3 weeks.
  • Mirvetuximab Soravtansine

Eligibility Criteria

Inclusion Criteria:

1. Age =/> 18 years.

2. ECOG performance status of 0 or 1.

3. Confirmed invasive triple-negative breast cancer defined as ER<10%; PR<10% by IHC and HER2 0-1+ by IHC or 2+, FISH < 2, gene copy number < 4.

4. (For Cohort A) - Archived tissue available at pre-screening to confirm FR alpha+ breast cancer.

5. (For Cohort A) Archived tissue available pre-screening to confirm FR alpha+ breast cancer. (For Cohort B) Confirmed FRalpha+ breast cancer defined as high FRalpha expression: =/>75% of cells having =/>1+ expression, or moderate FRalpha expression: 25%-74% of cells with =/>1+ expression.

6. (For Cohort A) Measurable disease per RECIST. (For cohort B) Clinical or radiologic primary tumor size of at least 1.5cm prior to enrollment onto protocol 2014-0185 (ARTEMIS). Primary tumor of at least 1.0 cm or evidence of continued lymphnode involvement by imaging (ultrasound or MRI) after Adriamycin-based neoadjuvant therapy.

7. (For cohort B): primary tumor sample collected before NACT started (on ARTEMIS) and underwent molecular testing for integral biomarkers including immunohistochemical assessment of FRalpha.

8. (For cohort A): no more than two prior therapies for metastatic disease. (Relapse of disease within 6 months of adjuvant or neoadjuvant chemotherapy is considered 1 line of therapy for metastatic disease). (For cohort B): received at least one dose of an anthracycline-based NACT. Patients are eligible if therapy was discontinued due to disease progression or therapy intolerance. Patients with disease progression on anthracycline-based therapy should be evaluated by the surgical team. If the patient is deemed inoperable at the time of evaluation, the patient may continue to undergo protocol therapy with a goal of reduction in tumor size to become operable. If the patient is deemed at high risk of becoming inoperable by the surgical team based upon tumor size or location, the patient will be considered ineligible for study and will be recommended to go to surgery.

9. (For cohort B): Primary tumor size of at least 1.0 cm by imaging (ultrasound or MRI) or evidence of continued lymph node involvement by imaging (ultrasound or MRI) after Adriamycin-based neoadjuvant therapy.

10. (For cohort B): baseline MUGA or echocardiogram showing LVEF =/> 50% within 6 weeks prior to initiation of NACT.

11. (For both cohorts A and B): Adequate bone marrow function as shown by: • ANC =/>1.5x10^9 /L, • Platelets =/ >100x10^9 /L, • Hb >9 G/dL.

12. (For both cohorts A and B): Adequate organ function as shown by: • Total serum bilirubin =/<2.0 mg/dL, • ALT and AST =/<2.5x ULN (=/<5x ULN in patients with liver metastases), • INR =/<2; • Serum creatinine =/<1.5x ULN; • Serum albumin >2.

13. Signed informed consent obtained prior to any screening procedures.

14. (For cohort A only): Time from prior therapy: a. Systemic anti-neoplastic therapy: five half-lives or four weeks, whichever is shorter. Hormonal therapy is not considered anti-neoplastic therapy. b. Radiotherapy: wide-field radiotherapy (e.g. > 30% of marrow-bearing bones) completed at least four weeks, or focal radiation completed at least two weeks, prior to starting study treatment

15. (For cohort B only): patients must have at least 3 and no more than 5 weeks between anthracycline-based therapy and start of treatment with mirvetuximab soravtansine.

16. (For both cohorts A and B): Patients must have resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia).

17. (For both cohorts A and B): WCBP must have a negative pregnancy test within 3 days prior to the first dose of study treatment.

Exclusion Criteria:

1. Pregnant or lactating women.

2. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study

3. (For Cohort B only): presence of metastatic disease or prior radiation therapy of the primary breast carcinoma or axillary lymph nodes.

4. Women of child-bearing potential (WCBP), defined as all women capable of becoming pregnant, won't use highly effective methods of contraception during the study and 12 weeks after. Highly effective contraception methods include combination of any two of the following: • Placement of an IUD or IUS; • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository; • Total abstinence or; • Male/female sterilization. Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile, or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to study entry. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential.

5. Male patients whose sexual partner(s) are WCBP who are not willing to use adequate contraception, during the study and for 12 weeks after the end of treatment.

6. Patients with > Grade 1 peripheral neuropathy.

7. Active or chronic corneal disorder, including but not limited to the following: Sjogren's syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and also active ocular conditions requiring on-going treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, and acquired monocular vision.

8. Serious concurrent illness or clinically-relevant active infection, including, but not limited to the following: • Known active hepatitis B or C • Known Human Immunodeficiency Virus (HIV) infection • Varicella-zoster virus (shingles) • Cytomegalovirus infection • Any other known concurrent infectious disease, requiring IV antibiotics within 2 weeks of study enrollment

9. Clinically- significant cardiac disease: • Recent myocardial infarction (=/<6 months prior to day 1), • Unstable angina pectoris, • Uncontrolled congestive heart failure (New York Heart Association > class II), • Uncontrolled hypertension (=/> CTCAE v4.03 Grade 3), • Prior history of hypertensive crisis or hypertensive encephalopathy, • Uncontrolled cardiac arrhythmias, • Clinically-significant vascular disease (e.g. aortic aneurysm, or dissecting aneurysm), • Severe aortic stenosis, • Clinically significant peripheral vascular disease, • =/> Grade 3 cardiac toxicity following prior chemotherapy • QTc >470 for females and >450 for males

10. History of neurological conditions that would confound assessment of treatment-emergent neuropathy.

11. History of hemorrhagic or ischemic stroke within the last 6 months

12. History of cirrhotic liver disease

13. Previous clinical diagnosis of non-infectious pneumonitis or non-infectious interstitial lung disease.

14. Prior hypersensitivity to monoclonal antibodies.

15. Patients who have a history of another primary malignancy, with the exceptions of: non-melanoma skin cancer, and carcinoma in situ of the cervix, uteri, or breast from which the patient has been disease free for =/>3 years

16. Carcinomatous meningitis, untreated central nervous system (CNS) disease or symptomatic CNS metastasis. Patients with previously treated CNS metastasis (excluding carcinomatous meningitis) may participate if they are stable (without evidence of progression by imaging, using identical imaging modality at each assessment, for at least 4 weeks prior to first dose of study treatment), have no evidence of new or emerging CNS metastasis, and are not using steroids for at least 7 days prior to first dose of study treatment.

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

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

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response Rate of Mirvetuximab Soravtansine in Participants with Metastatic FRa+ Triple-Negative Breast Cancer (TNBC)
Time Frame:6 months
Safety Issue:
Description:Response defined as confirmed complete response (CR) or partial response (PR) per RECIST.

Secondary Outcome Measures

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Malignant neoplasm of breast
  • Triple-Negative Breast Cancer
  • TNBC
  • Metastatic Triple-Negative Breast Cancer
  • Newly Diagnosed Triple-Negative Breast Cancer
  • Mirvetuximab Soravtansine
  • IMGN853

Last Updated

April 4, 2017