A Compassionate Use Study of Leronlimab in Breast Cancer

This is a single arm, compassionate use study with 30 patients for leronlimab (PRO 140) combined with a treatment of physician's choice (TPC) in patients with CCR5+ mTNBC.

This is a single arm, compassionate use study with 30 patients for leronlimab (PRO 140) combined with a treatment of physician's choice (TPC) in patients with CCR5+ mTNBC.

Leronlimab (PRO 140) will be administered subcutaneously as weekly dose of 350 mg until disease progression or intolerable toxicity. Treatment of Physician's Choice (TPC) is defined as one of the following single-agent chemotherapy drugs administrated according to local practice: eribulin, gemcitabine, capecitabine, paclitaxel, nab-paclitaxel, vinorelbine, ixabepilone, or carboplatin. The selected treatment should be administered as per the dosing schedule included on the package insert.

In this study, patients will be evaluated for tumor response approximately every 3 months or according to institution's standard practice by CT, PET/CT or MRI with contrast (per treating investigator's discretion) using the same method as at baseline. Tumor measurements will be done using RECIST v1.1.

Eligibility Criteria:
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% of primary or metastatic tumor cells shows membranous staining and/or high predominance of CCR5+ tumor-infiltrating leukocytes completed at the reference laboratory).
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. Subjects with locally recurrent or metastatic breast cancer who have been treated with ≥ 3 previous chemotherapy drugs (including neo/adjuvant setting) and had progressed or were intolerant to the latest chemotherapy. Previous treatment under neo/adjuvant setting must have included an anthracycline and a taxane, unless the patient was not suitable for these treatments.

   Note: Patients progressed on atezolizumab or other checkpoint inhibitor will be eligible for participation in the study.
5. Patients must have measurable disease based on RECIST v1.1;
6. Female patients, ≥ 18 years of age;
7. Patients must exhibit a/an ECOG performance status of 0-1;
8. Life expectancy of at least 6 months;
9. 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.
10. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator.
11. 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).
12. 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
13. Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study.

Exclusion Criteria:

1. HER-2 overexpressed/amplified MBC (Appendix 2 for guidelines from ASCO);
2. ER and or PR expressing tumors;
3. PD-L1 positive subjects who are eligible to receive atezolizumab;
4. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days prior to enrollment;
5. Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible;
6. Patients who have had prior exposure to CCR5 antagonists are not eligible;
7. Patients who have a known additional malignancy that is progressing or requires active treatment are not eligible. Patients who have had a prior diagnosis of cancer and if it has been \<3 years since their last treatment are not eligible. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer;
8. Has an active infection requiring systemic therapy. Note: Patients must complete any treatment with antibiotics prior to registration;
9. Patients who have a known HIV positive status or known/ active Hepatitis B and/or C infection are not eligible;
10. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability;
11. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator;
12. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial; and
13. Is pregnant or breastfeeding, or expecting to conceive or have children within the projected duration of the trial, starting with the pre-screening or screening visit through the duration of study participation.