Trial for Treatment of High Risk BC With Two Sequences of Neoadjuvant Chemotherapy With Pembrolizumab

NCT06371807 | Not Yet Recruiting Phase 2

• 1 other identifier: EU CTR n.º 2023-507008-30-00
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

Phase II, randomized, Active-controlled open label trial for treatment of high risk, HR-/HER2- (triple negative) breast cancer, with two sequences of neoadjuvant chemotherapy on a background of pembrolizumab

Conditions

Early Breast Cancer; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (3)

• Detect immunologic activation signal and the immunologically defined most suitable patient population for the synergistic interaction between pembrolizumab and chemotherapy backbone

  Compare signals of immunological activation or a more favorable immunological context beetween T cell subpopulations and transcriptional changes of T cell populations infiltrating tumors at baseline and C2D1

  At the end of cycle 1 (each cycle is 28 days)

• Rate of pCR

  Compare the rate of pCR in subjects with locally advanced TNBC with TILs ≥ 10% in arm A and arm B at cycle 4

  6 months to one year after subject inclusion

• Primary translational endpoint

  Quantification of number of T cells per mm2 with different phenotypes using fate bifurcation as defined as the proportion of TILs with the phenotype T-bet(hi) PD1(mid) CD8+.

  6 months to one year after subject inclusion

Secondary Outcomes (2)

• Changes in the immunogenic phenotype

  6 months to one year after subject inclusion

• Incidence of treatment relatred Adverse events

  6 months to one year after subject inclusion

Study Arms (2)

Arm 1: (KXCb - PA[E]C)

ACTIVE COMPARATOR

Pembrolizumab (K) every 3 weeks (Q3W) + paclitaxel (X) + carboplatin (Cb) once weekly (QW) for 4 cycles in the neoadjuvant setting followed by pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) for 4 cycles followed by pembrolizumab every 6 weeks for 5 cycles (total of 1 year of pembrolizumab) in the adjuvant setting.

Drug: Pembrolizumab injection

(KPA[E]C - KXCb)

EXPERIMENTAL

Pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) for 4 cycles in the neoadjuvant setting followed by pembrolizumab (K) every 3 weeks (Q3W) + paclitaxel (X) + carboplatin (Cb) once weekly (QW) for 4 cycles followed by pembrolizumab every 6 weeks for 5 cycles (total of 1 year of pembrolizumab) in the adjuvant setting

Drug: Pembrolizumab injection

Interventions

Pembrolizumab injection DRUG

(KXCb - PA\[E\]C) vs (KPA\[E\]C - KXCb) Pembrolizumab (K) + paclitaxel (X) + carboplatin (Cb) followed by pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) followed by pembrolizumab in the adjuvant setting vs Pembrolizumab + doxorubicin or epirubicin (A or E) + cyclophosphamide (C) followed by pembrolizumab (K) + paclitaxel (X) + carboplatin (Cb) followed by pembrolizumab in the adjuvant setting

Also known as: Doxorubicin or Epirubicin, Cyclophosphamide, Paclitaxel, Carboplatin

(KPA[E]C - KXCb); Arm 1: (KXCb - PA[E]C)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
• Be a female or male participant who is at least 18 years of age on the day of signing informed consent.
• Have locally histologically confirmed diagnosis of invasive carcinoma of the breast that is classified as TNBC, as defined by the most recent ASCO/CAP guidelines.
• Has locally confirmed tumor infiltrating lymphocytes (stromal) (sTILs) equal to or above 10%, as defined by the most recent International Guidelines on TIL Assessment in Breast Cancer.
• Have previously untreated non-metastatic (M0) TNBC defined as the following combined primary tumor (T) and regional lymph node (N) staging per current AJCC staging criteria for breast cancer staging criteria as assessed by the investigator based on radiological and/or clinical assessment:
• T1c, N1-N2
• T2, N0-N2
• T3, N0-N2
• T4a-d, N0-N2 Note: bilateral tumors (ie, synchronous cancers in both breasts) and/or multi-focal (ie, 2, separate lesions in the same quadrant)/multi-centric (ie, 2 separate lesions in different quadrants) tumors are allowed, as well as inflammatory breast cancer, and the tumor with the most advanced T stage should be used to assess the eligibility. If the subject has either bilateral or multi-focal/multi-centric disease, TNBC needs to be confirmed in at least 2 lesions/breast/focus. Beyond this rule, the extent of tumor biopsy confirmation is based on the best clinical judgment by local investigators.
• Provide a core needle biopsy consisting of at least 3 separate tumor cores from the primary tumor at screening to the designated central biobank (or responsible laboratories) and is willing to provide a second biopsy at the end of the first cycle of treatment.
• Note: Detailed instructions on sample collection, processing, storage and shipment to the central biobank are provided in the Laboratory Manual.
• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days of treatment initiation.
• Have left ventricular ejection fraction (LVEF) of ≥50% or ≥ institution lower limit of normal (LLN) as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed at screening.
• Have adequate organ function as defined in the following table (Table 2). Specimens must be collected within 28 days prior to the start of study intervention.
• Male participants:

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Has a history of invasive malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
• Has received prior chemotherapy, targeted therapy, and radiation therapy within the past 12 months.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
• Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 4 weeks of the first dose of treatment in this current trial.
• Note: subject should be excluded if he/she received an investigational agent with anticancer or anti-proliferative intent within the last 12 months.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• 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 prior to the first dose of study drug.
• 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 and is allowed.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has significant cardiovascular disease, such as:
• History of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the last 6 months
• Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA class III or IV
• Has a known history of Human Immunodeficiency Virus (HIV) infection.
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection.

Sponsors & Collaborators

• Fundacao Champalimaud: lead

Study Sites (3)

Fundaçao Champalimaud, Avenida Brasilia,

Lisbon, 1400-038, Portugal

Location

Centro Hospitalar Universitário Lisboa Norte E.P.E

Lisbon, 1649-028, Portugal

Location

Instituto Português de Oncologia Francisco Gentil, E.P.E

Porto, 4200-072, Portugal

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

pembrolizumab; Doxorubicin; Epirubicin; Cyclophosphamide; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Fatima Cardoso, MD

  Breast Unit Director

  STUDY DIRECTOR

Central Study Contacts

Marcio Debiasi, MD

CONTACT

+351 210480048; marcio.debiasi@fundacaochampalimaud.pt

Inês Sousa, MSc

CONTACT

+351 210480048; ines.sousa@fundacaochampalimaud.pt

Study Design

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

Model Details: Randomized

Study Record Dates

• First Submitted: March 12, 2024
• First Posted: April 17, 2024
• Study Start: July 1, 2024
• Primary Completion: July 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 17, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Within one year of primary analysies

Locations

PT (3)