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

NCT03838367 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: CD07_TNBC
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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).

Conditions

Triple Negative Breast Neoplasms

Keywords

TNBC; PRO 140

Outcome Measures

Primary Outcomes (2)

• Phase I: Maximum Tolerated Dose (MTD) of Leronlimab (PRO 140) When Combined With Carboplatin AUC5

  The MTD is defined as 1 dose level (cohort) below the dose in which dose limiting toxicities (DLTs) were observed in \>= 33% of the participants.

  From treatment cycle 1 day 1 (C1D1) until MTD reached (each cycle being 3 weeks), up to 26 weeks

• 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.

  All patients who received at least one dose of leronlimab (PRO 140) and carboplatin combination was intended to be included in the primary analyses of PFS. The Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria was planned to be used for objective tumor response assessment.

  Planned every 6 to 9 weeks after Phase II study start, until progression or death, assessing up to 2 years after completion of treatment

Secondary Outcomes (7)

• Phase I: Number of Participants With Any Adverse Events (AE) or Serious Adverse Events (SAE) Collected From the Time of First Treatment Until Study Termination to Evaluate Safety of Leronlimab (PRO 140) and Carboplatin in Subjects With CCR5+ mTNBC.

  From Cycle 1, Day 1 (each treatment cycle is 3 weeks) until last dose of study drug, up to 26 weeks

• Phase II: Progression Free Survival (PFS) According to RECIST v1.1 in Participants With Detectable Programmed Death-Ligand 1 (PD-L1)

  Planned every 6 to 9 weeks after Phase II study start, until progression or death, assessing 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.

  Planned every 6 to 9 weeks after Phase II study start, until progression or death, assessing up to 2 years after completion of treatment

• Phase II: Time to New Metastases (TTNM)

  Planned every 6 to 9 weeks after Phase II study start, until progression or death, assessing up to 2 years after completion of treatment

• Phase II: The Change From Baseline in Circulating Tumor Cells (CTC) Level in the Peripheral Blood.

  Planned every 21 days (i.e., Day 1 of each treatment cycle) through treatment completion, an average of 6 months.

Other Outcomes (2)

• Measure Immune Biomarkers (PD-L1) in CTCs, Metastatic Tissue and Immune Cells Such as Cancer Associated Macrophage-like Cells (CAMLs) and Correlate With Therapeutic Benefit (PFS)

  Planned 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.

  Planned every 21 days (i.e., Day 1 of each treatment cycle) through treatment completion, an average of 6 months.

Study Arms (4)

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

EXPERIMENTAL

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

Drug: 350 mg leronlimab; Drug: AUC 5 Carboplatin

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

EXPERIMENTAL

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

Drug: 525 mg leronlimab; Drug: AUC 5 Carboplatin

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

EXPERIMENTAL

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

Drug: 700 mg leronlimab; Drug: AUC 5 Carboplatin

Phase II- MTD to be established for the combination treatment

EXPERIMENTAL

MTD PRO 140 SC + AUC 5 Carboplatin

Drug: AUC 5 Carboplatin; Drug: Maximum Tolerated Dose (MTD) of leronlimab

Interventions

350 mg leronlimab DRUG

leronlimab is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5.

Also known as: PRO 140

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

525 mg leronlimab DRUG

leronlimab is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5.

Also known as: PRO 140

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

700 mg leronlimab DRUG

leronlimab is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5.

Also known as: PRO 140

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

AUC 5 Carboplatin DRUG

Carboplatin is an anticancer drug chemotherapy drug.

Also known as: Paraplatin

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

Maximum Tolerated Dose (MTD) of leronlimab DRUG

The decision on the MTD will be made following the results obtained from Phase I studies

Also known as: PRO 140

Phase II- MTD to be established for the combination treatment

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female patients, \>=18 years of age
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• 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.
• 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;
• 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;

You may not qualify if:

• HER-2 overexpressed/amplified metastatic breast cancer (MBC) (Appendix 2 for guidelines from ASCO);
• ER and or PR expressing tumors;
• 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.

Sponsors & Collaborators

• CytoDyn, Inc.: lead
• Amarex Clinical Research: collaborator

Study Sites (2)

Quest Clinical Research

San Francisco, California, 94115, United States

Location

CD07 Investigational Site

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

leronlimab; Carboplatin; Maximum Tolerated Dose

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Toxicity Tests; Investigative Techniques; Toxicological Phenomena; Pharmacological and Toxicological Phenomena; Physiological Phenomena

Limitations and Caveats

Trial was terminated prematurely prior to Phase II section of the study.

Results Point of Contact

• Title: Joseph Meidling - Vice President, Clinical Operations
• Organization: CytoDyn

jmeidling@cytodyn.com

3609808524

Study Officials

• Jacob Lalezari, MD

  CytoDyn, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2019
• First Posted: February 12, 2019
• Study Start: April 22, 2019
• Primary Completion: July 15, 2022
• Study Completion: September 16, 2022
• Last Updated: September 9, 2025
• Results First Posted: September 9, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)