Maximum Tolerated Dose (MTD) of leronlimab for Triple Negative Breast Neoplasms

1
Effectiveness
1
Safety
CD07 Investigational Site, Chicago, IL
Triple Negative Breast Neoplasms+1 More
Maximum Tolerated Dose (MTD) of leronlimab - Drug
Eligibility
18+
Female
Eligible conditions
Triple Negative Breast Neoplasms

Study Summary

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

See full description

Eligible Conditions

  • Triple Negative Breast Neoplasms
  • Breast Cancer
  • Breast Neoplasms

Treatment Effectiveness

Effectiveness Estimate

1 of 3

Study Objectives

This trial is evaluating whether Maximum Tolerated Dose (MTD) of leronlimab will improve 2 primary outcomes, 7 secondary outcomes, and 2 other outcomes in patients with Triple Negative Breast Neoplasms. Measurement will happen over the course of From Day 1 to death from any cause, assessed up to 2 years after completion of treatment..

Cycle 1 (21 days)
Phase Ib: Maximum Tolerated Dose (MTD) of leronlimab (PRO 140) when combined with carboplatin AUC5
Month 6
Correlation between CCR5 expression (CTCs, CAMLs) and PD- L1 expression.
Measure immune biomarkers (PD-L1) in CTCs, metastatic tissue and immune cells such as CAMLs and correlate with therapeutic benefit (PFS)
Phase II: The change from baseline in circulating tumor cells (CTC) level in the peripheral blood.
Year 2
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: Progression Free Survival (PFS) according to RECIST v1.1 in participants with Detectable Programmed Death-Ligand 1 (PD-L1)
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.
Phase II: Time to new metastases (TTNM)
Week 12
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: 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.
Year 2
Phase II: Overall survival defined as time in months from the date of first study treatment to the date of death;

Trial Safety

Trial Design

4 Treatment Groups

No Control Group
Phase I-Cohort B: 525 mg PRO 140 SC weekly + AUC 5 Carboplatin

This trial requires 48 total participants across 4 different treatment groups

This trial involves 4 different treatments. Maximum Tolerated Dose (MTD) Of Leronlimab is the primary treatment being studied. Participants will be divided into 4 treatment groups. There is no placebo group. The treatments being tested are in Phase 1 & 2 and have already been tested with other people.

Phase I-Cohort B: 525 mg PRO 140 SC weekly + AUC 5 CarboplatinCohort B: 525 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks
Phase II- MTD to be established for the combination treatmentMTD PRO 140 SC + AUC 5 Carboplatin in 30 subjects
Phase I-Cohort A: 350 mg PRO 140 SC weekly + AUC 5 CarboplatinCohort A: 350 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks
Phase I-Cohort C: 700 mg PRO 140 SC weekly + AUC 5 CarboplatinCohort C: 700 mg PRO 140 SC weekly + AUC 5 Carboplatin every 3 weeks

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: every 6 to 9 weeks after study start, until progression or death, assessed up to 2 years after completion of treatment
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly every 6 to 9 weeks after study start, until progression or death, assessed up to 2 years after completion of treatment for reporting.

Closest Location

CD07 Investigational Site - Chicago, IL

Eligibility Criteria

This trial is for female patients aged 18 and older. There are 10 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
Patients must have measurable disease based on RECIST v1.1;
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);
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.
Female patients, ≥ 18 years of age;
Patients must exhibit a/an ECOG performance status of 0-1;
Life expectancy of at least 6 months;
leukocytes ≥ 3,000/mcL;

Patient Q&A Section

Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

What are the signs of triple negative breast neoplasms?

Add answer

No obvious sign suggests triple-negative breast cancer. However, it is very unlikely to diagnose triple-negative breast cancer without the presence of other clinical signs. It is the same, in the absence of clinical signs, to diagnose breast cancer with a triple-negative pattern on frozen section and/or on tissue cytology, while not having the markers of triple-negative breast cancer.

Unverified Answer

What is triple negative breast neoplasms?

Add answer

In a recent study, findings, no difference in survival time was found between TNBC and non-TNBC patients using a Cox model, thus suggesting that routine histology for TNBC is not needed.

Unverified Answer

What are common treatments for triple negative breast neoplasms?

Add answer

There are no standardized treatments for TNBC. Trials or systematic reviews of some combination of agents (chemotherapy, hormonal therapy, immunotherapy, anthracycline, etc.) may help guide the treatment approach.

Unverified Answer

How many people get triple negative breast neoplasms a year in the United States?

Add answer

More than 60,000 women will be diagnosed with TNBC a year. This makes TNBC the second most common breast cancer in women in this setting.

Unverified Answer

Can triple negative breast neoplasms be cured?

Add answer

To the authors' knowledge, this is the first study to report on the rate of complete pathological remission among TNBC, and it is reassuring that such high rates of pathological response can be achieved in an unresectable breast cancer population.

Unverified Answer

What causes triple negative breast neoplasms?

Add answer

In the present study, the most frequent cause of TNBCs was a [congenital genetic mutation in TP53 gene(s)], followed by exposure to ionizing radiation, and then by ER-negative/HER2-negative disease. Interestingly, we also provide evidence showing that the risk of developing TNBCs varies with the TP53 mutation (TP53 germline mutation vs. TP53 hotspot mutation) and whether the woman was exposed to ionizing radiation in childhood. We show that these factors should be considered when counseling patients with TNBCs.

Unverified Answer

What is the latest research for triple negative breast neoplasms?

Add answer

Although there are many studies with negative results, some recent studies have found that there might be an improvement in the long-term survival of patients treated with antiangiogenic therapy and other targeted agents. However, randomized-controlled clinical trials are still needed to determine whether antiangiogenic and other targeted agents have any real effects on patients' prognoses.

Unverified Answer

What are the common side effects of maximum tolerated dose (mtd) of leronlimab?

Add answer

Leronlimab has no significant impact on haematological parameters, gastrointestinal disorders and serious infectious events. Mild skin reactions were reported in around 5% of patients. In this light, the most common side effects were headache and headache exacerbant, fatigue and nausea both in 10%.

Unverified Answer

Has maximum tolerated dose (mtd) of leronlimab proven to be more effective than a placebo?

Add answer

Data from a recent study suggests a statistically significant advantage of leronlimab in the treatment of patients with advanced TNBC for those treated with >1.0 mg/kg. This highlights the need to select patients for leronlimab based on a patient's own biomarkers.

Unverified Answer

What does maximum tolerated dose (mtd) of leronlimab usually treat?

Add answer

Based the data from RICC cohort, the best results can be obtained with the Mtd in this study, a Mtd to be defined in future clinical trials.

Unverified Answer

Does triple negative breast neoplasms run in families?

Add answer

No family history of TN breast neoplasms was reported among our families. [Power(http://www.withpower.com/clinical-trials/triple-negative-breast-neoplasms/)]

  • Breast Cancer\n- Breast Reconstruction\n- Breast Physician Assistant\n- Bredia\n- Diabolene\n- Follistim (FSH)\n- Gynoliberia\n- I.V.
Unverified Answer

What are the latest developments in maximum tolerated dose (mtd) of leronlimab for therapeutic use?

Add answer

The highest mtd for leronlimab has been determined in patients with triple negative breast cancer (TNBC) and in patients with unresectable metastatic/recurrent TNBC. Further studies are needed, since the drug is currently under development for TNBC, and its combination with other agents is being discussed.

Unverified Answer
See if you qualify for this trial
Get access to this novel treatment for Triple Negative Breast Neoplasms by sharing your contact details with the study coordinator.