Phase II Study of Pembrolizumab and Nab-paclitaxel in HER-2 Negative Metastatic Breast Cancer

NCT02752685 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 15-00441
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm open-label multi-cohort Phase II study evaluating the safety/tolerability and clinical activity of the combination of nab-paclitaxel and the antibody against programmed cell death 1 (PD-1), pembrolizumab, in patients with human epidermal growth factor receptor (HER-2) negative metastatic breast cancer (n=50). There will be two cohorts of patients consisting of a triple negative breast cancer (TNBC) cohort with 30 subjects and a hormone receptor (HR)-positive cohort with 20 subjects. There will be an initial safety run-in with 12 subjects from the TNBC and HR-positive cohort (\~ 6 patients from each cohort). If no unexpected toxicity is observed (as defined in the study protocol), then enrollment will continue to complete both cohorts (30 total TNBC, 20 total in HR positive cohort). The subjects from the run in safety part will be included in the Phase II analysis. Tumor expression of programmed cell death ligand 1 (PD-L1) is not required for enrollment in the study, but will be assessed as possible predictive marker.

Conditions

Breast Cancer

Keywords

Nab-Paclitaxel; Abraxane; MK-3475

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Best Overall Response Rate (BORR) of Complete Response or Partial Response

  Overall response measured by RECIST version 1.1 and will be used in this study for assessment of tumor response. Complete response (CR) defined as disappearance of all target lesions; and partial response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Up to Year 2

Secondary Outcomes (4)

• Progression Free Survival (PFS)

  Up to Year 2

• Overall Survival (OS)

  Up to Year 2

• Disease Control Rate (DCR)

  Up to Year 2

• Duration of Response (DOR)

  Up to Year 2

Study Arms (3)

HR-Positive Participants

EXPERIMENTAL

Participants with HR-positive metastatic breast cancer will receive nab-paclitaxel 100 mg/m2 on days 1 and 8 of the first 21-day treatment cycle. On the second 21-day treatment cycle, the participants will receive pembrolizumab 200 mg IV on the first day of the cycle, in addition to nab-paclitaxel 100 mg/m2 on days 1 and 8 of the cycle.

Drug: Pembrolizumab; Drug: Nab-Paclitaxel

cTNBC Participants

EXPERIMENTAL

Participants with TNBC-positive metastatic breast cancer who in the chemotherapy run-in group (cNTBC) will receive nab-paclitaxel 100 mg/m2 on days 1 and 8 of the first 21-day cycle. On the second 21-day treatment cycle, the participants will receive pembrolizumab 200 mg IV on the first day of the cycle, in addition to nab-paclitaxel 100 mg/m2 on days 1 and 8 of the cycle.

Drug: Pembrolizumab; Drug: Nab-Paclitaxel

iTNBC Participants

EXPERIMENTAL

Participants with TNBC-positive metastatic breast cancer in the immunotherapy run-in group (cNTBC) will receive pembrolizumab 200mg IV on day 1 of the first 21-day treatment cycle. nab-paclitaxel 100 mg/m2 on days 1 and 8 of the first 21-day cycle. On the second 21-day cycle, the participants will receive nab-paclitaxel 100 mg/m2 on days 1 and 8 of the cycle, in addition to pembrolizumab 200mg IV on day 1 of the cycle.

Drug: Pembrolizumab; Drug: Nab-Paclitaxel

Interventions

Pembrolizumab DRUG

Also known as: MK-3475

HR-Positive Participants; cTNBC Participants; iTNBC Participants

Nab-Paclitaxel DRUG

Also known as: Abraxane

HR-Positive Participants; cTNBC Participants; iTNBC Participants

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have histologically confirmed adenocarcinoma of the breast that is either TNBC or HR positive/HER-2 negative. TNBC is defined as: ER/PR \<1% and HER-2 negative disease (IHC 0-1+ or 2+ with HER2/17 ratio on FISH ≤1.8) according to ASCO/CAP guidelines11,67. HR positive is defined as: ER/PR \>= 1% and HER-2 negative as per ASCO/CAP guidelines.
• Have received 0-2 lines of cytotoxic chemotherapy for metastatic breast cancer endocrine therapy and/or targeted therapy is allowed.
• Be willing and able to provide written informed consent/assent for the trial
• Be 18 years of age on day of signing informed consent.
• Have measurable disease based on RECIST 1.1.
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the PI or designee.
• Have a performance status of 0 or 1 on the ECOG Performance Scale. Be willing to undergo tissue biopsies as mandatory as per protocol for patients with biopsy accessible disease.
• Must have \</= Grade 1 pre-existing peripheral neuropathy (as per CTCAE).
• Demonstrate adequate organ function as defined in all screening labs should be performed within 10 days of treatment initiation.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. This applies even if the subject practices true abstinence\* from heterosexual contact. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• A female subject of childbearing potential is a sexually mature women who (1) has not undergone hysterectomy \[the surgical removal of the uterus\] or bilateral oophorectomy \[the surgical removal of both ovaries\] or (2) has not been naturally postmenopausal for at least 24 consecutive months \[i.e., has had menses at any time during the preceding 24 consecutive months\]. The female subject must: either commit to true abstinence\* from heterosexual contact (which must be reviewed on a monthly basis), or agree to use, and be able to comply with, effective contraception without interruption (2 methods of birth control), 28 days prior to starting IP therapy (including dose interruptions), and while on study medication or for a longer period if required by local regulations following the last dose of IP.
• Male subjects must practice true abstinence\* or agree to use a condom during sexual contact with a pregnant female or female of childbearing potential starting with the first dose of study therapy, during dose interruptions, and for up to 6 months following last dose of study therapy, even if he has undergone a successful vasectomy.

You may not qualify if:

• 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 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis).
• Hypersensitivity to pembrolizumab or any of its excipients
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Taxane therapy within the past 3 months (90 days) prior to study Day 1.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that progressed or required treatment within the last five years. 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 known active central nervous system (CNS) metastases and/or carcinomatous meningitis. 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 active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of/active pneumonitis requiring treatment with steroids or history of/active interstitial lung disease.
• Has an active infection requiring systemic therapy.
• 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.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Perlmutter Cancer Center

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pembrolizumab; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Sylvia Adams, MD
• Organization: NYU Langone Health

Sylvia.Adams@nyulangone.org

212-731-5795

Study Officials

• Natalie Klar, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2016
• First Posted: April 27, 2016
• Study Start: June 1, 2016
• Primary Completion: December 29, 2022
• Study Completion: December 1, 2025
• Last Updated: January 29, 2025
• Results First Posted: March 6, 2024

Record last verified: 2025-01

Locations

US (1)