Mirvetuximab Soravtansine as First Line in Treating Patients With Triple Negative Breast Cancer

NCT03106077 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2016-0683NCI-2018-01213
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well mirvetuximab soravtansine works as first line in treating patients with triple negative breast cancer. Drugs used in chemotherapy, such as mirvetuximab soravtansine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Conditions

Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Estrogen Receptor Negative; Folate Receptor Alpha Positive; HER2/Neu Negative; Progesterone Receptor Negative; Prognostic Stage II Breast Cancer AJCC v8; Prognostic Stage IIA Breast Cancer AJCC v8; Prognostic Stage IIB Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (2)

• Number of Metastatic Participants With Radiographic Response

  Determine if Mirvetuximab Soravtansine as a Single Agent is Likely to Induce Response in at Least 20% of Patients With Metastatic Folate Receptor (FR) Alpha+ Triple Negative Breast Cancer (TNBC). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  From the registration to the study until disease progression or death from any cause, whichever occurred first, assessed up to 2 years

• Number of Neoadjuvant Participants With Pathologic Response

  Determine if mirvetuximab soravtansine as a single agent in the neoadjuvant setting will improve rates of excellent pathologic response (pathologic complete response \[pCR\]/residual cancer burden \[RCB\]-0 or RCB-I) from 5% to 20% in patients with high risk, chemotherapy insensitive, FRalpha+ TNBC.

  From baseline to the study until disease progression or surgery, assessed up to 6 months

Secondary Outcomes (5)

• Number of Participants With Radiographic Response Rate

  From the baseline to the study until disease progression or death from any cause, whichever occurred first

• Number of Participants With Stable Disease

  From the baseline to the study until disease progression or death from any cause, whichever occurred first

• Number of Participants With Progressive Disease

  From the baseline to the study until disease progression or death from any cause, whichever occurred first

• Number of Metastatic Participants With Duration of Response

  From the date of enrollment/baseline of the study until disease progression or death from any cause, whichever occurred first, up to 2 years

• Compare Participants Disease Response FRalpha+ Chemotherapy Resistant Disease vs Similar Molecular Features Who Receive Standard Taxane-based Chemotherapy

  From the date of enrollment/baseline of the study until disease progression or death from any cause, whichever occurred first

Study Arms (2)

Cohort A (mirvetuximab soravtansine)

EXPERIMENTAL

Patients receive mirvetuximab soravtansine IV over 2-3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unaccepted toxicity.

Biological: Mirvetuximab Soravtansine

Cohort B (mirvetuximab soravtansine)

EXPERIMENTAL

Patients receive mirvetuximab soravtansine IV over 2-3 hours on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unaccepted toxicity.

Biological: Mirvetuximab Soravtansine

Interventions

Mirvetuximab Soravtansine BIOLOGICAL

Given IV

Also known as: IMGN853, M9346A-sulfo-SPDB-DM4

Cohort A (mirvetuximab soravtansine); Cohort B (mirvetuximab soravtansine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Confirmed invasive triple-negative breast cancer defined as estrogen receptor (ER) \< 10%; progesterone receptor (PR) \< 10% by immunohistochemistry (IHC) and HER2 0-1+ by IHC or 2+, fluorescence in situ hybridization (FISH) \< 2, gene copy number \< 4
• (For Cohort A) - Archived tissue available at pre-screening to confirm FR alpha+ breast cancer
• (For Cohort A) Archived tissue available pre-screening to confirm FR alpha+ breast cancer. (For Cohort B) Confirmed FRalpha+ breast cancer defined as low FRalpha expression: \>= 25% of cells having \>= 1+ expression
• (For Cohort A) Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST). (For cohort B) Clinical or radiologic primary tumor size of at least 1.5 cm prior to enrollment onto protocol 2014-0185 (ARTEMIS). Primary tumor of at least 1.0 cm or evidence of continued lymph node involvement by imaging (ultrasound or magnetic resonance imaging \[MRI\]) after adriamycin-based neoadjuvant therapy
• (For cohort B): Primary tumor sample collected before NACT started (on ARTEMIS) and underwent molecular testing for integral biomarkers including immunohistochemical assessment of FRalpha
• (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
• (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
• (For cohort B): Baseline multigated acquisition (MUGA) or echocardiogram showing left ventricular ejection fraction (LVEF) \>= 50% within 6 weeks prior to initiation of NACT
• (For both cohorts A and B): Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• (For both cohorts A and B): Platelets \>= 100 x 10\^9/L
• (For both cohorts A and B): Hemoglobin (Hb) \> 9 G/dL
• (For both cohorts A and B): Total serum bilirubin =\< 2.0 mg/dL
• (For both cohorts A and B): Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x upper limit of normal (ULN) (=\< 5 x ULN in patients with liver metastases)
• (For both cohorts A and B): International normalized ratio (INR) =\< 2

You may not qualify if:

• Pregnant or lactating women
• 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
• (For Cohort B only): Presence of metastatic disease or prior radiation therapy of the primary breast carcinoma or axillary lymph nodes
• 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 intrauterine device (IUD) or intrauterine system (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
• 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
• Patients with \> grade 1 peripheral neuropathy
• 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
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

mirvetuximab soravtansine

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Stacy Moulder, Professor, Breast Medical Oncology
• Organization: UT MD Anderson Cancer Center

smoulder@mdanderson.org

(713) 792-2817

Study Officials

• Stacy L Moulder

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2017
• First Posted: April 10, 2017
• Study Start: June 5, 2017
• Primary Completion: October 1, 2019
• Study Completion: October 1, 2019
• Last Updated: December 2, 2020
• Results First Posted: November 19, 2020

Record last verified: 2020-11

Locations

US (1)