search
Back to results

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

Primary Purpose

Triple Negative Breast Neoplasms

Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
350 mg leronlimab
525 mg leronlimab
700 mg leronlimab
AUC 5 Carboplatin
Maximum Tolerated Dose (MTD) of leronlimab
Sponsored by
CytoDyn, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Triple Negative Breast Neoplasms focused on measuring TNBC, PRO 140

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Quest Clinical Research
  • CD07 Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase I-Cohort A: 350 mg PRO 140 SC weekly + AUC 5 Carboplatin

Phase I-Cohort B: 525 mg PRO 140 SC weekly + AUC 5 Carboplatin

Phase I-Cohort C: 700 mg PRO 140 SC weekly + AUC 5 Carboplatin

Phase II- MTD to be established for the combination treatment

Arm Description

Cohort A: 350 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks

Cohort B: 525 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks

Cohort C: 700 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks

MTD PRO 140 SC + AUC 5 Carboplatin in 30 subjects

Outcomes

Primary Outcome Measures

Phase Ib: Maximum Tolerated Dose (MTD) of leronlimab (PRO 140) when combined with carboplatin AUC5
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.

Secondary Outcome Measures

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.
Phase II: Progression Free Survival (PFS) according to RECIST v1.1 in participants with Detectable Programmed Death-Ligand 1 (PD-L1)
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.
Phase II: Time to new metastases (TTNM)
Phase II: The change from baseline in circulating tumor cells (CTC) level in the peripheral blood.
Phase II: Overall survival defined as time in months from the date of first study treatment to the date of death;
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.

Full Information

First Posted
February 5, 2019
Last Updated
March 18, 2022
Sponsor
CytoDyn, Inc.
Collaborators
Amarex Clinical Research
search

1. Study Identification

Unique Protocol Identification Number
NCT03838367
Brief Title
Leronlimab (PRO 140) Combined With Carboplatin in Patients With CCR5+ mTNBC
Official Title
A Phase Ib/II Study of Leronlimab (PRO 140) Combined With Carboplatin in Patients With CCR5+ Metastatic Triple Negative Breast Cancer (mTNBC)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Unknown status
Study Start Date
April 22, 2019 (Actual)
Primary Completion Date
July 15, 2022 (Anticipated)
Study Completion Date
September 16, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CytoDyn, Inc.
Collaborators
Amarex Clinical Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Triple Negative Breast Neoplasms
Keywords
TNBC, PRO 140

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase I-Cohort A: 350 mg PRO 140 SC weekly + AUC 5 Carboplatin
Arm Type
Experimental
Arm Description
Cohort A: 350 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks
Arm Title
Phase I-Cohort B: 525 mg PRO 140 SC weekly + AUC 5 Carboplatin
Arm Type
Experimental
Arm Description
Cohort B: 525 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks
Arm Title
Phase I-Cohort C: 700 mg PRO 140 SC weekly + AUC 5 Carboplatin
Arm Type
Experimental
Arm Description
Cohort C: 700 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks
Arm Title
Phase II- MTD to be established for the combination treatment
Arm Type
Experimental
Arm Description
MTD PRO 140 SC + AUC 5 Carboplatin in 30 subjects
Intervention Type
Drug
Intervention Name(s)
350 mg leronlimab
Other Intervention Name(s)
PRO 140
Intervention Description
leronlimab is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5.
Intervention Type
Drug
Intervention Name(s)
525 mg leronlimab
Other Intervention Name(s)
PRO 140
Intervention Description
leronlimab is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5.
Intervention Type
Drug
Intervention Name(s)
700 mg leronlimab
Other Intervention Name(s)
PRO 140
Intervention Description
leronlimab is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5.
Intervention Type
Drug
Intervention Name(s)
AUC 5 Carboplatin
Intervention Description
Carboplatin is an anticancer drug chemotherapy drug.
Intervention Type
Drug
Intervention Name(s)
Maximum Tolerated Dose (MTD) of leronlimab
Other Intervention Name(s)
PRO 140
Intervention Description
The decision on the MTD will be made following the results obtained from Phase I studies
Primary Outcome Measure Information:
Title
Phase Ib: Maximum Tolerated Dose (MTD) of leronlimab (PRO 140) when combined with carboplatin AUC5
Time Frame
Cycle 1 (21 days)
Title
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
Secondary Outcome Measure Information:
Title
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)
Title
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
Title
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
Title
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
Title
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.
Title
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.
Title
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)
Other Pre-specified Outcome Measures:
Title
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.
Title
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.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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); 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; Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion (in case archival tissue is not available); 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. Patients must have measurable disease based on RECIST v1.1; Female patients, ≥ 18 years of age; Patients must exhibit a/an ECOG performance status of 0-1; Life expectancy of at least 6 months; 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. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator. 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). 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 Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study. Exclusion Criteria: HER-2 overexpressed/amplified MBC (Appendix 2 for guidelines from ASCO); ER and or PR expressing tumors; Subjects who have had previous systemic chemotherapy for metastatic breast cancer; 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; Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible; Patients who have had prior exposure to CCR5 antagonists are not eligible; 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; Has an active infection requiring systemic therapy. Note: Patients must complete any treatment with antibiotics prior to registration; Patients who have a known HIV positive status or known/ active Hepatitis B and/or C infection are not eligible; 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; 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; Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial; and 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.
Facility Information:
Facility Name
Quest Clinical Research
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
CD07 Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs