This phase I trial studies the side effects and best dose of mirvetuximab soravtansine and gemcitabine hydrochloride in treating patients with folate receptor (FR) alpha-positive ovarian, primary peritoneal, fallopian tube, endometrial, or triple negative breast cancer that has come back. Mirvetuximab soravtansine is a monoclonal antibody, called mirvetuximab, linked to a chemotherapy drug called DM4. Mirvetuximab attaches to FOLR1 positive cancer cells in a targeted way and delivers DM4 to kill them. Drugs used in the chemotherapy, such as gemcitabine hydrochloride, 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. Giving mirvetuximab soravtansine and gemcitabine may work better in treating patients with FRalpha-positive ovarian, primary peritoneal, fallopian tube, endometrial, or triple negative breast cancer.
PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of gemcitabine hydrochloride (gemcitabine) when given in combination with mirvetuximab soravtansine (IMGN853) to patients with FRalpha-positive recurrent ovarian, primary peritoneal, fallopian tube, endometrial cancer, or triple negative breast cancer (TNBC). SECONDARY OBJECTIVES: I. To explore the toxicity, response rate (RR) and progression free survival (PFS) in three expanded cohorts of heavily pre-treated FRalpha-positive a) TNBC patients; b) endometrial cancer patients; and c) ovarian, primary peritoneal, or fallopian tube cancer patients, all treated at the initial recommended phase II dose. II. To provide additional safety data from the expanded cohorts to help inform on the RP2D for each cohort. III. To evaluate the relationship between intratumoral levels of DM4, tumoral expression of FRalpha, and plasma concentration of DM4 at 48 and 72 hours following the first dose. IV. To determine the pharmacokinetics (PK) of DM4 and gemcitabine when given in combination. EXPLORATORY OBJECTIVE: I. To evaluate the role of archival FRalpha expression as a substitute for the 48-72 hour (H) expression in determining intratumoral concentration of DM4. OUTLINE: This is a dose escalation study. Patients receive mirvetuximab soravtansine intravenously (IV) on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Cycles repeat every 3 weeks in the absence of disease progression or unexpected toxicity. After completion of study treatment, patients are follow up at 30 days and then every 12 weeks thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
44
Given IV
Given IV
Correlative studies
Given IV
Correlative studies
City of Hope Medical Center
Duarte, California, United States
City of Hope Upland
Upland, California, United States
Recommended phase II dose assessed by Common Terminology Criteria for Adverse Events version 4
Tables will be created to summarize toxicities by dose level, cycles delivered, and total dose delivered, and side effects by dose and by cycle.
Time frame: Up to 3 weeks
Incidence of treatment-emergent adverse events and clinically significant >= grade 3 changes assessed by Common Terminology Criteria for Adverse Events version 4.0
Will assess the type, severity and attribution, time to onset, and duration.
Time frame: Up to 2 years
Response
Will be assessed by Response Evaluation Criteria in Solid Tumors 1.1.
Time frame: Up to 2 years
Progression free survival
Time frame: Time from study entry to disease progression, assessed up to 2 years
Assessment of biological correlatives assessed by biopsy
Time frame: Up to 2 years
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