Phase II Open-label, Single-arm Trial of Neoadjuvant Pembrolizumab With Carboplatin and Paclitaxel in Triple-negative Breast Cancer

Tel Aviv Medical Center0 sites25 target enrollmentJuly 1, 2024

Overview

Brief Summary

This is a phase II, single-centered, open-label, single-armed study in patients with early triple-negative breast cancer that will evaluate the pathological complete response (pCR) rate of a non-anthracycline-based chemo-immunotherapy regimen. The trial includes a lead-in cycle of pembrolizumab, then a combination of paclitaxel, carboplatin, and pembrolizumab in the neoadjuvant setting.

Detailed Description

The cure rate of stage I and II triple-negative breast cancer treated with anthracycline-based chemotherapy is high but comes at the price of substantial toxicity. This is a phase II, single-centered, open-label, single-armed study in patients with early triple-negative breast cancer that will evaluate the pathological complete response (pCR) rate and immune effects of a non-anthracycline-based chemo-immunotherapy regimen. The trial includes a lead-in cycle of pembrolizumab, then a combination of paclitaxel, carboplatin, and pembrolizumab in the neoadjuvant setting.

Registry

clinicaltrials.gov

Start Date

July 1, 2024

End Date

December 1, 2027

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Tel Aviv Medical Center

Responsible Party

Principal Investigator

Yasmin Leshem

Senior Medical Oncologist

Tel Aviv Medical Center

Eligibility Criteria

Inclusion Criteria

•Male/female participants who are at least 18 years of age on the day of signing informed consent with a histologically confirmed diagnosis of stage I or II TNBC.
•Tumor size of above 1 cm.
•The patient is willing to provide tissue from newly obtained core biopsies.
•Male participants:
•A male participant must agree to use contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 200 days after the last dose of study treatment and refrain from donating sperm during this period.
•Female participants:
•A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
•Not a woman of childbearing potential (WOCBP). OR
•A WOCBP who agrees to follow the contraceptive during the treatment period and for at least 180 days after the last dose of chemotherapy.
•The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.

Exclusion Criteria

•A WOCBP who has a positive urine pregnancy test within 72 hours prior of the first treatment dose (. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
•Has received prior therapy with an anti-Programmed cell death-ligand-1 (PD-L1), anti-PD-1, or anti-PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte associated protein 4 (CTLA-4), OX 40, CD137).
•Has received prior systemic anti-cancer therapy, including investigational agents, within 24 months of screening.
•Has received prior radiotherapy within 24 months of screening.
•Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
•Note: please refer to Section 5.5.2 for information on coronavirus disease 2019 (COVID-19) vaccines
•Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration.
•Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of the study drug.
•Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
•Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.

Arms & Interventions

neoadjuvant pembrolizumab with carboplatin and paclitaxel in triple-negative breast cancer

6 cycles of Pembrolizumab (Keytruda) at a dose of 200 mg given every 3 weeks for 6 cycles. The first cycle of pembrolizumab is given as a lead-in without carboplatin and paclitaxel. Carboplatin area under the curve (AUC) 1.5 and Paclitaxel 80 mg/m2, starting with the second pembrolizumab cycle, will be given weekly for 12 weeks.

Intervention: Pembrolizumab

neoadjuvant pembrolizumab with carboplatin and paclitaxel in triple-negative breast cancer

6 cycles of Pembrolizumab (Keytruda) at a dose of 200 mg given every 3 weeks for 6 cycles. The first cycle of pembrolizumab is given as a lead-in without carboplatin and paclitaxel. Carboplatin area under the curve (AUC) 1.5 and Paclitaxel 80 mg/m2, starting with the second pembrolizumab cycle, will be given weekly for 12 weeks.

Intervention: Carboplatin

neoadjuvant pembrolizumab with carboplatin and paclitaxel in triple-negative breast cancer

6 cycles of Pembrolizumab (Keytruda) at a dose of 200 mg given every 3 weeks for 6 cycles. The first cycle of pembrolizumab is given as a lead-in without carboplatin and paclitaxel. Carboplatin area under the curve (AUC) 1.5 and Paclitaxel 80 mg/m2, starting with the second pembrolizumab cycle, will be given weekly for 12 weeks.

Intervention: Paclitaxel

Outcomes

Primary Outcomes

Pathological complete response rate (pCR= ypT0/Tis ypN0)

Time Frame: 3 years

The number of patients with pathological complete response (pCR) out of the total number of trial participants using a definition of ypT0/Tis ypN0 after treatment with neoadjuvant pembrolizumab, paclitaxel and carboplatin (PCb).

Molecular dynamics of cells in the tumor microenvironment (TME)

Time Frame: 3 years

The molecular state of cells in the TME will be measured at a single-cell level using single-cell RNA sequencing (scRNA-seq) before and after one dose of pembrolizumab.