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

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

Study Drug Administration:

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

Length of Study:

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

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

Study Visits:

On Day 1 of each cycle:

- Participant will have a physical exam.

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

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

Participant will come back to the clinic on Day 2 of Cycles 1-3. At these visits,
participant's vital signs will be collected and the study doctor or study staff will check on
participant's 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):

- Participant will have imaging scans. The study doctor will tell participant what type of
scans participant will have.

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

End-of-Treatment Visit:

As soon as possible after participant's last cycle of study drug:

- Participant will have a physical exam.

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

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

- Participant will have imaging scans.

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

If participant is in Cohort B, participant will have surgery as part of participant's
standard treatment.

Follow-Up:

Within 30 days after participant's last dose of study drug:

- Participant will have a physical exam.

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

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

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

Participant will continue to have imaging scans every 12 weeks for up to 1 year after
participant's first dose of study drug. If the disease gets worse or participant starts 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.

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
involement 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 limit on 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 involovement 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)