Clinical Trials /

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

NCT03838367

Description:

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).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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)

Clinical Trial IDs

  • ORG STUDY ID: CD07_TNBC
  • NCT ID: NCT03838367

Conditions

  • Triple Negative Breast Neoplasms

Interventions

DrugSynonymsArms
350 mg leronlimabPRO 140Phase I-Cohort A: 350 mg PRO 140 SC weekly + AUC 5 Carboplatin
525 mg leronlimabPRO 140Phase I-Cohort B: 525 mg PRO 140 SC weekly + AUC 5 Carboplatin
700 mg leronlimabPRO 140Phase I-Cohort C: 700 mg PRO 140 SC weekly + AUC 5 Carboplatin
AUC 5 CarboplatinPhase I-Cohort A: 350 mg PRO 140 SC weekly + AUC 5 Carboplatin
Maximum Tolerated Dose (MTD) of leronlimabPRO 140Phase II- MTD to be established for the combination treatment

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase I-Cohort A: 350 mg PRO 140 SC weekly + AUC 5 CarboplatinExperimentalCohort A: 350 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks
  • 350 mg leronlimab
  • AUC 5 Carboplatin
Phase I-Cohort B: 525 mg PRO 140 SC weekly + AUC 5 CarboplatinExperimentalCohort B: 525 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks
  • 525 mg leronlimab
  • AUC 5 Carboplatin
Phase I-Cohort C: 700 mg PRO 140 SC weekly + AUC 5 CarboplatinExperimentalCohort C: 700 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks
  • 700 mg leronlimab
  • AUC 5 Carboplatin
Phase II- MTD to be established for the combination treatmentExperimentalMTD PRO 140 SC + AUC 5 Carboplatin in 30 subjects
  • AUC 5 Carboplatin
  • Maximum Tolerated Dose (MTD) of leronlimab

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% 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase Ib: Maximum Tolerated Dose (MTD) of leronlimab (PRO 140) when combined with carboplatin AUC5
Time Frame:Cycle 1 (21 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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.
Safety Issue:
Description:
Measure: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.
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:CytoDyn, Inc.

Trial Keywords

  • TNBC
  • PRO 140

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