T-Cell Therapy for Advanced Breast Cancer

NCT02792114 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 16-040
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to test the safety of different doses of specially prepared T cells collected from the blood. The investigators want to find a safe dose of these modified T cells for patients who have metastatic HER2-negative breast cancer.

Conditions

Breast Cancer; Metastatic HER2-negative Breast

Keywords

T-Cell; Chimeric antigen receptor (CAR); CAR T cells; Triple-negative breast cancer; Immunotherapy T-cell therapy; 16-040; immunotherapy; CAR

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated does (MTD)

  We have designed the dose-escalation using a standard 3+3 design. In this design, patients will be treated in sequential groups of 3 to 6 patients per T cell dose. With 4 dose levels, the projected trial size for this study is a minimum of 4 and a maximum of 24 patients.

  2 years

Study Arms (1)

T-cell infusion

EXPERIMENTAL

A single blood volume leukapheresis for harvesting of PBMCs will be performed, As the transduced T cells will be frozen, the timing of leukapheresis is not defined \& can vary from patient to patient. Subsequently, a single dose of mesothelin-targeted T cells will be infused via intravenous catheter or central line (i.e., mediport). Patients will be monitored in the hospital and discharged home after a minimum of 48 hours. Patients will be monitored closely as outpatients for the next 2 months. Patients will be followed weekly as outpatients for the first 8 weeks after treatment. All patients will be hydrated intravenously, premedicated with acetaminophen \& diphenhydramine, \& administered cyclophosphamide at 1.5 g/m2 2 to 7 days (Day -7 to Day -2) before administration of mesothelin-targeted T cells.

Drug: Cyclophosphamide; Biological: Mesothelin-targeted T cells; Drug: AP1903

Interventions

Cyclophosphamide DRUG

T-cell infusion

Mesothelin-targeted T cells BIOLOGICAL

T-cell infusion

AP1903 DRUG

T-cell infusion

Eligibility Criteria

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

You may qualify if:

• Patients aged ≥18 years with metastatic breast cancer
• Karnofsky performance status ≥70%
• Patients with breast cancer that is pathologically confirmed at MSKCC (pathology from outside institutions is acceptable for the screening phase of the protocol) and defined by the following:
• HER2 negative (in cases of mixed HER2 results, the most recent pathology results considered reflective of the active cancer will be considered)
• Previously treated with at least 1 chemotherapy regimen for metastatic disease and documented progression
• Expression of mesothelin must be confirmed by meeting 1 of the following criteria:
• Mesothelin expression (\>10% of the tumor expressing mesothelin) by IHC
• Elevated serum SMRP levels (\>1.0 nM/L)
• Presence of measurable or evaluable disease
• Chemotherapy, targeted therapy (such as a tyrosine kinase inhibitor), or radiotherapy must have been completed at least 14 days before administration of T-cells. Prior immunotherapy with checkpoint blockade (i.e., PD1 inhibitor, PDL1 inhibitor, or CTL4-antagonist or similar agent) must have been completed more than 1 month before the T-cell infusion.
• \*Chemotherapy must have been completed at least 7 days prior to leukapheresis
• Any major operation must have occurred at least 28 days before study enrollment.
• All acute toxic effects of any previous radiotherapy, chemotherapy, or surgical procedures must have resolved to grade 1 or lower according to CTCAE
• Lab requirements (hematology):
• White blood cell (WBC) count ≥3000 cells/mm\^3

You may not qualify if:

• Untreated or active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control); patients with a history of treated CNS metastases are eligible, provided that all of the following criteria are met:
• Presence of measurable or evaluable disease outside of the CNS;
• Radiographic demonstration of improvement upon completion of CNS- directed therapy and no evidence of interim progression between completion of CNS-directed therapy and the screening radiographic study;
• Completion of radiotherapy ≥8 weeks prior to the screening radiographic study;
• Discontinuation of corticosteroids and anticonvulsants ≥4 weeks prior to the screening radiographic study.
• History of seizure disorder
• Patients currently receiving treatment for concurrent active malignancy. Prior immunotherapy with checkpoint blockade (i.e., PD1 inhibitor, PDL1 inhibitor, or CTL4-antagonist or similar agent) must have been completed more than 1 month prior to the T-cell infusion.
• Autoimmune or antibody-mediated disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and temporal arteritis (patients with a history of hypothyroidism will not be excluded)
• Clinically significant cardiac disease (New York Heart Association class III/IV) or severe debilitating pulmonary disease
• Pregnant or lactating women
• Known active infection requiring antibiotics within 7 days of the start of treatment (Day 0)
• A requirement for daily systemic corticosteroids for any reason or a requirement for other immunosuppressive or immunomodulatory agents. Topical, nasal, and inhaled steroids are permitted.
• Administration of live, attenuated vaccine within 8 weeks before the start of treatment (Day 0) and throughout the study
• Any other medical condition that, in the opinion of the PI, may interfere with a subject's participation in or compliance with the study
• Participation in a therapeutic research study or receipt of an investigational drug within 30 days of T-cell infusion

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• United States Department of Defense: collaborator

Study Sites (7)

Memorial Sloan Kettering Cancer Center (Consent and follow-up only)

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Monmouth (Consent and follow-up only)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Consent and follow-up only)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Center at Commack (Consent and follow-up only)

Commack, New York, United States

Location

Memorial Sloan Kettering Westchester (Consent and follow-up only)

East White Plains, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Consent and Follow-Up only)

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Cyclophosphamide; AP 1903 reagent

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Shanu Modi, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2016
• First Posted: June 7, 2016
• Study Start: June 1, 2016
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: July 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)