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Leronlimab (PRO 140) Combined With Carboplatin in Patients With CCR5+ mTNBC

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ClinicalTrials.gov Identifier: NCT03838367
Recruitment Status : Recruiting
First Posted : February 12, 2019
Last Update Posted : May 16, 2019
Sponsor:
Collaborator:
Amarex Clinical Research
Information provided by (Responsible Party):
CytoDyn, Inc.

Tracking Information
First Submitted Date  ICMJE February 5, 2019
First Posted Date  ICMJE February 12, 2019
Last Update Posted Date May 16, 2019
Actual Study Start Date  ICMJE April 22, 2019
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 9, 2019)
  • Phase Ib: Maximum Tolerated Dose (MTD) of leronlimab (PRO 140) when combined with carboplatin AUC5 [ Time Frame: Cycle 1 (21 days) ]
  • Phase II: Progression free survival (PFS) defined as time in months from the date of first study treatment to the date of disease progression or death from any cause, whichever comes first. [ Time Frame: Every 6 to 9 weeks after study start, until progression or death, assessed up to 2 years after completion of treatment ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03838367 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2019)
  • Phase I: The number, frequency, and severity of adverse events (AEs) collected from the time of first treatment until 12 weeks after study treatment completion to evaluate safety of leronlimab (PRO 140) and carboplatin in subjects with CCR5+ mTNBC. [ Time Frame: From Cycle 1, Day 1 (each treatment cycle is 21 days) to 12 weeks after the last dose of study drug) ]
  • Phase II: Progression Free Survival (PFS) according to RECIST v1.1 in participants with Detectable Programmed Death-Ligand 1 (PD-L1) [ Time Frame: Every 6 to 9 weeks after study start, until progression or death, assessed up to 2 years after completion of treatment ]
  • Phase II: Overall response rate (ORR, defined as Complete Response (CR) + Partial Response (PR)), and clinical benefit rate (CBR, defined as CR + PR + Stable Disease (SD)) in subjects with CCR5+ mTNBC treated with leronlimab (PRO 140) and carboplatin. [ Time Frame: Every 6 to 9 weeks after study start, until progression or death, assessed up to 2 years after completion of treatment ]
  • Phase II: Time to new metastases (TTNM) [ Time Frame: Every 6 to 9 weeks after study start, until progression or death, assessed up to 2 years after completion of treatment ]
  • Phase II: The change from baseline in circulating tumor cells (CTC) level in the peripheral blood. [ Time Frame: Every 21 days (i.e., Day 1 of each treatment cycle) through treatment completion, an average of 6 months. ]
  • Phase II: Overall survival defined as time in months from the date of first study treatment to the date of death; [ Time Frame: From Day 1 to death from any cause, assessed up to 2 years after completion of treatment. ]
  • Phase II: The number, frequency, and severity of AEs collected from the time of first treatment until 12 weeks after study treatment completion to evaluate safety of leronlimab (PRO 140) and carboplatin in subjects with CCR5+ mTNBC. [ Time Frame: From Cycle 1, Day 1 (each treatment cycle is 21 days) to 12 weeks after the last dose of study drug) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 9, 2019)
  • Phase I: The number, frequency, and severity of adverse events (AEs) collected from the time of first treatment until 12 weeks after study treatment completion to evaluate safety of leronlimab (PRO 140) and carboplatin in subjects with CCR5+ mTNBC. [ Time Frame: From Cycle 1, Day 1 (each treatment cycle is 21 days) to 12 weeks after the last dose of study drug) ]
  • Phase II: PFS according to RECIST v1.1 in participants with Detectable Programmed Death-Ligand 1 (PD-L1) [ Time Frame: Every 6 to 9 weeks after study start, until progression or death, assessed up to 2 years after completion of treatment ]
  • Phase II: Overall response rate (ORR, defined as Complete Response (CR) + Partial Response (PR)), and clinical benefit rate (CBR, defined as CR + PR + Stable Disease (SD)) in subjects with CCR5+ mTNBC treated with leronlimab (PRO 140) and carboplatin. [ Time Frame: Every 6 to 9 weeks after study start, until progression or death, assessed up to 2 years after completion of treatment ]
  • Phase II: Time to new metastases (TTNM) [ Time Frame: Every 6 to 9 weeks after study start, until progression or death, assessed up to 2 years after completion of treatment ]
  • Phase II: The change from baseline in circulating tumor cells (CTC) level in the peripheral blood. [ Time Frame: Every 21 days (i.e., Day 1 of each treatment cycle) through treatment completion, an average of 6 months. ]
  • Phase II: Overall survival defined as time in months from the date of first study treatment to the date of death; [ Time Frame: From Day 1 to death from any cause, assessed up to 2 years after completion of treatment. ]
  • Phase II: The number, frequency, and severity of AEs collected from the time of first treatment until 12 weeks after study treatment completion to evaluate safety of leronlimab (PRO 140) and carboplatin in subjects with CCR5+ mTNBC. [ Time Frame: From Cycle 1, Day 1 (each treatment cycle is 21 days) to 12 weeks after the last dose of study drug) ]
Current Other Pre-specified Outcome Measures
 (submitted: February 9, 2019)
  • Measure immune biomarkers (PD-L1) in CTCs, metastatic tissue and immune cells such as CAMLs and correlate with therapeutic benefit (PFS) [ Time Frame: Every 21 days (i.e., Day 1 of each treatment cycle) through treatment completion, an average of 6 months. ]
  • Correlation between CCR5 expression (CTCs, CAMLs) and PD- L1 expression. [ Time Frame: Every 21 days (i.e., Day 1 of each treatment cycle) through treatment completion, an average of 6 months. ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Leronlimab (PRO 140) Combined With Carboplatin in Patients With CCR5+ mTNBC
Official Title  ICMJE A Phase Ib/II Study of Leronlimab (PRO 140) Combined With Carboplatin in Patients With CCR5+ Metastatic Triple Negative Breast Cancer (mTNBC)
Brief Summary

This is a phase Ib/II Study of Leronlimab (PRO 140) combined with Carboplatin in Patients with CCR5+ Metastatic Triple Negative Breast Cancer (mTNBC).

Study population will consist of patients with CCR5-positive, locally advanced or metastatic triple-negative breast cancer (mTNBC) who are naïve to chemotherapy in metastatic setting but have been exposed to anthracyclines and taxane in neoadjuvant and adjuvant settings (first-line).

Detailed Description

Phase Ib

Phase Ib is a dose escalation phase with 3 dose levels (cohorts) of leronlimab (PRO 140) administered in combination with a fixed dose of carboplatin at AUC 5. This dose finding portion of study will follow a "3+3" designed to determine the maximum tolerated dose (MTD) of leronlimab (PRO 140) administered as subcutaneous injection in subjects with histologically confirmed mTNBC that express CCR5.

Phase II

Phase II is a single arm study with 30 patients in order to test the hypothesis that the combination of carboplatin AUC 5 intravenously and MTD of leronlimab (PRO 140) SC will increase PFS in patients with CCR5 + mTNBC.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Triple Negative Breast Neoplasms
Intervention  ICMJE
  • Drug: 350 mg leronlimab
    leronlimab is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5.
    Other Name: PRO 140
  • Drug: 525 mg leronlimab
    leronlimab is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5.
    Other Name: PRO 140
  • Drug: 700 mg leronlimab
    leronlimab is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5.
    Other Name: PRO 140
  • Drug: AUC 5 Carboplatin
    Carboplatin is an anticancer drug chemotherapy drug.
  • Drug: Maximum Tolerated Dose (MTD) of leronlimab
    The decision on the MTD will be made following the results obtained from Phase I studies
    Other Name: PRO 140
Study Arms  ICMJE
  • Experimental: Phase I-Cohort A: 350 mg PRO 140 SC weekly + AUC 5 Carboplatin
    Cohort A: 350 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks
    Interventions:
    • Drug: 350 mg leronlimab
    • Drug: AUC 5 Carboplatin
  • Experimental: Phase I-Cohort B: 525 mg PRO 140 SC weekly + AUC 5 Carboplatin
    Cohort B: 525 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks
    Interventions:
    • Drug: 525 mg leronlimab
    • Drug: AUC 5 Carboplatin
  • Experimental: Phase I-Cohort C: 700 mg PRO 140 SC weekly + AUC 5 Carboplatin
    Cohort C: 700 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks
    Interventions:
    • Drug: 700 mg leronlimab
    • Drug: AUC 5 Carboplatin
  • Experimental: Phase II- MTD to be established for the combination treatment
    MTD PRO 140 SC + AUC 5 Carboplatin in 30 subjects
    Interventions:
    • Drug: AUC 5 Carboplatin
    • Drug: Maximum Tolerated Dose (MTD) of leronlimab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 9, 2019)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2022
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. Subjects must be untreated or naïve to chemotherapy and/or checkpoint inhibitors exposure in metastatic setting and have been exposed to anthracyclines and taxane in neoadjuvant and adjuvant settings (first-line); 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. 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. Subjects who have had previous systemic chemotherapy for metastatic breast cancer;
  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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kush Dhody, MBBS, MS, CCRA 301-956-2536 kushd@amarexcro.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03838367
Other Study ID Numbers  ICMJE CD07_TNBC
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party CytoDyn, Inc.
Study Sponsor  ICMJE CytoDyn, Inc.
Collaborators  ICMJE Amarex Clinical Research
Investigators  ICMJE Not Provided
PRS Account CytoDyn, Inc.
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP