Leronlimab (PRO 140) Combined With Carboplatin in Patients With Cytokine Chemokine Receptor 5 Positive (CCR5+) mTNBC

Inclusion Criteria

• •1. Must have a histologically confirmed diagnosis of TNBC. Must demonstrate HER-2 negative (IHC 0, 1+, or fluorescence in situ hybridization (FISH) negative and ER\<1%, and PR \< 1%, per ASCO/CAP criteria);
• •2. Demonstrate CCR5 + by IHC (\>10% membranous staining completed at the reference laboratory of Dr. Hallgeir Rui at Medical College of Wisconsin).
• •Note: This test will be done as part of the pre-screening period. It will be performed in archival metastatic tissue. If archival tissue is not available then, fresh biopsy will be done;
• •3. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion (in case archival tissue is not available);
• •4. Patients with stage IV de-novo disease or patients that develop recurrence after completion of neoadjuvant or adjuvant therapy are eligible; Note: Patients who have been exposed to carboplatin in neoadjuvant or adjuvant setting will be allowed to enroll, if they have progressed ≥ 6 months from completion of treatment.
• •5. Phase 1 study section:
• •Subjects must have disease recurrence and progression after ≤ 2 line of therapy in metastatic setting but untreated with carboplatin;
• •Phase 2 study section:
• •Subjects must be naive to chemotherapy or untreated with carboplatin in metastatic setting (first-line) OR excluding carboplatin chemotherapy, subjects must have failed first-line combination of chemotherapy and a checkpoint inhibitor in metastatic setting;
• •6. Patients must have measurable disease based on RECIST v1.1;
• •7. Female patients, ≥ 18 years of age;
• •8. Patients must exhibit a/an ECOG performance status of 0-1;
• •9. Life expectancy of at least 6 months;
• •10. Patients must have adequate organ and bone marrow function within 28 days prior to registration, as defined below:
• •* leukocytes ≥ 3,000/mcL;
• •* absolute neutrophil count ≥ 1,500/mcL;
• •* platelets ≥ 100,000/mcL;
• •* total bilirubin: within normal institutional limits;
• •* AST(SGOT) \&ALT(SPGT) ≤ 2.5 X institutional upper limit of normal (ULN) (applicable to all patients, irrespective of liver disease or metastasis); and
• •* creatinine: within normal institutional limits.
• •11. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator.
• •12. Females of child-bearing potential (FOCBP) and males must agree to use two medically accepted methods of contraception with hormonal or barrier method of birth control, or abstinence, prior to study entry, for the duration of study participation and for 60 days after the last dose of study drug (Refer to Appendix 1). Should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Note: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• •* Has not undergone a hysterectomy or bilateral oophorectomy; and
• •* Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months).
• •13. FOCBP must have a negative serum pregnancy test at Screening Visit and negative urine pregnancy test prior to receiving the first dose of study drug; and
• •14. Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study.