Pembrolizumab + Paclitaxel in HR+/HER2- Non-luminal (by PAM50) Advanced Breast Cancer After CDK4/6 Inhibitor Progression

NCT04251169 | Terminated Phase 2 Results DMC

• 2 other identifiers: SOLTI-17162018-003367-58
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 7

Brief Summary

This is an open-label, single arm, multicenter phase II study evaluating treatment with pembrolizumab in combination with paclitaxel in patients with locally advanced or metastatic non-luminal hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) (hereafter referred to as HR+/HER2-) breast cancer who had recurrence or progression while receiving previous therapy with a cyclin-dependent kinase (CDK) inhibitor in the adjuvant setting or to treat advanced disease (or both).

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate of Pembrolizumab in Combination With Paclitaxel in HR+/HER2- Non-luminal Subtype Advanced Breast Cancer Defined by the PAM50 Assay

  ORR defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR), as per local investigator´s assessment and according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria

  From the date of randomization to disease progression, death, unacceptable toxicity, consent withdrawal, or study termination, whichever occurred first, assessed for up to 33 months.

Secondary Outcomes (8)

• Clinical Benefit Rate (CBR)

  From the date of randomization to disease progression, death, unacceptable toxicity, consent withdrawal, or study termination, whichever occurred first, assessed for up to 33 months.

• Progression Free Survival (PFS)

  From the date of randomization to disease progression, death, unacceptable toxicity, consent withdrawal, or study termination, whichever occurred first, assessed for up to 33 months.

• Duration of Response (DoR)

  From the date of randomization to disease progression, death, unacceptable toxicity, consent withdrawal, or study termination, whichever occurred first, assessed for up to 33 months.

• Time to Response (TtR)

  From the date of randomization to disease progression, death, unacceptable toxicity, consent withdrawal, or study termination, whichever occurred first, assessed for up to 33 months.

• Overall Survival (OS)

  From date of randomization to death, unacceptable toxicity, consent withdrawal or study termination, whichever came first, assessed after a median follow-up of 26 months (interquartile range [IQR]: 16.6-not reached [NR]).

Study Arms (1)

Pembrolizumab + Paclitaxel

EXPERIMENTAL

Pembrolizumab 200 mg every 3 weeks (on Day 1 \[D1\] of each 21-day cycle, beginning in Cycle 1) in combination with paclitaxel 80 mg/m² administered at Days 1, 8, and 15 of each 21-day cycle beginning at Cycle 2.

Drug: Pembrolizumab; Drug: Paclitaxel

Interventions

Pembrolizumab DRUG

Pembrolizumab 200 mg will be administered as a 30-minute intravenous (IV) infusion every 3 weeks beginning in Cycle 1

Also known as: Keytruda

Pembrolizumab + Paclitaxel

Paclitaxel DRUG

Paclitaxel will be administered at the 80 mg/m2 dose via 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of every 21-day cycle (beginning in Cycle 2). On days of scheduled infusions of pembrolizumab and paclitaxel (i.e., Day 1 of every cycle), paclitaxel is to be administered after infusion of pembrolizumab

Also known as: NSC-125973

Pembrolizumab + Paclitaxel

Eligibility Criteria

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

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of locally advanced or metastatic, histologically documented hormone receptor positive (estrogen receptor \[ER\] and/or progesterone receptor \[PR\] expression \>1%) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer by local testing, not amenable to surgical therapy will be enrolled in this study.
• HER2 negativity is defined as either of the following by local laboratory assessment: Immunohistochemistry (IHC) 0, IHC 1+ or IHC 2+/in situ hybridisation (ISH) negative as per American Society of Clinical Oncology (ASCO)-College of American Pathologists Guideline (CAP) guideline (ISH negative is defined as a ratio of HER2 to chromosome 17 centromere (CEP17) \<2.0)117.
• ER and/or PR positivity are defined as \>1% of cells expressing HR via IHC analysis as per ASCO-CAP guideline118
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Eligible for taxane therapy.
• No prior chemotherapy for inoperable locally advanced or metastatic breast cancer.
• Prior radiation therapy for metastatic disease is permitted. Subjects who were treated with radiation therapy may participate as long as at least 2 weeks have elapsed since the last dose of radiation therapy or have recovered from the effects of radiation before allocation whichever is the latest.
• Disease refractory to CDK4/6 inhibitors, defined as recurrence during or within 12 months after the end of adjuvant treatment or progression during or within 6 months after the end of treatment for advanced/metastatic disease.
• Notes: CDK4/6 inhibitors do not have to be the last treatment prior to randomization. Other prior anticancer endocrine therapy, e.g. aromatase inhibitors, fulvestrant or tamoxifen, are also allowed.
• Previous chemotherapy with a taxane for early breast cancer (neoadjuvant or adjuvant setting) is permitted.
• Availability of formalin-fixed paraffin-embedded (FFPE) tumor block, collected during advanced/metastatic disease, with an associated pathology report. The tumor tissue should be of good quality based on total and viable tumor content and must be evaluated centrally for PAM50 analysis prior to enrollment. Patients whose tumor tissue is not evaluable for central testing are not eligible. If PAM50 analysis of tumor sample has alredy been performed at central lab (i.e analysis from other SOLTI clinical trial) PAM50 result can be valid for this study.
• Acceptable samples include core needle biopsies for deep tumor tissue or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions or biopsies from bone metastases.
• Fine needle aspiration, brushing, cell pellet from pleural effusion and lavage samples are not acceptable.
• Non-Luminal subtype as per PAM50 analysis (i.e. HER2-enriched or Basal-like).
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 10 days prior to the date of allocation/randomization.

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to Cycle 1, Day 1 (C1D1). 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-PD1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.
• History of hypersensitivity reactions to paclitaxel or other drugs formulated in the same solvent as paclitaxel (polyoxyethylated castor oil).
• Resolution of all acute toxic effects of prior anti-cancer therapy or major surgical procedures to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) Grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator´s discretion).
• Note: Placement of central venous access catheter(s) (e.g., port or similar) is not considered a major surgical procedure and is therefore permitted.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Note: It is not recommended the use of live or attenuated COVID-19 vaccines within 30 days of initiation or during study treatment. However, if vaccination with these vaccines is required, please ask for advice on how to proceed the Medical Monitor.
• Uncontrolled pleural effusion, pericardial effusion, or ascites (Note: patients with indwelling catheters, such as PleurX® are allowed).
• Uncontrolled hypercalcemia (\>1.5 mmol/L \[\>6 mg/dL\] ionized calcium or serum calcium \[uncorrected for albumin\] \>3 mmol/L \[\>12 mg/dL\] or corrected serum calcium \>upper limit of normal (ULN) or clinically significant (symptomatic) hypercalcemia
• 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 a 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 (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has known active Central Nervous System metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• 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 a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Prior allogeneic stem cell or solid organ transplantation

Sponsors & Collaborators

• SOLTI Breast Cancer Research Group: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (7)

ICO Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Location

Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital Universitario 12 de octubre

Madrid, Spain

Location

Hospital Quiron Salud Sagrado Corazon Sevilla

Seville, Spain

Location

Fundación Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pembrolizumab; Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

Although the study fulfilled the criteria for Stage II, enrollment was prematurely discontinued due to financial constraints and a limited supply of pembrolizumab.

Results Point of Contact

• Title: Sara Cano
• Organization: SOLTI

info@gruposolti.org

34 664 449 862

Study Officials

• Aleix Prat, MD, PhD

  Hospital Clinic, Barcelona, Spain

  PRINCIPAL INVESTIGATOR

• Eva Ciruelos, MD, PhD

  Hospital 12 de Octubre, Madrid, Spain

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: January 30, 2020
• First Posted: January 31, 2020
• Study Start: July 21, 2020
• Primary Completion: April 10, 2024
• Study Completion: April 30, 2024
• Last Updated: June 3, 2025
• Results First Posted: June 3, 2025

Record last verified: 2025-05

Locations

ES (7)