Paclitaxel Plus Pembrolizumab vs. Paclitaxel Weekly in ER+ Luminal B Metastatic Breast Cancer (PELICAN)

A Phase II, Randomized Study of Paclitaxel Weekly Plus Pembrolizumab Versus Paclitaxel Weekly in ER-positive, Luminal B Metastatic Breast Cancer

PELICAN is a randomised phase II trial that aims to evaluate the efficacy and safety of paclitaxel plus pembrolizumab relative to paclitaxel alone, in patients with locally advanced or metastatic ER-positive, HER2-negative, Luminal B breast cancer who have received no prior chemotherapy for advanced or metastatic disease.

Patients will be randomised (2:1) to one of the two treatment arms:

• Pembrolizumab plus Paclitaxel
• Paclitaxel

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Paclitaxel

Detailed Description

PELICAN is a randomised phase II trial that aims to evaluate the efficacy and safety of paclitaxel plus pembrolizumab relative to paclitaxel alone, in patients with locally advanced or metastatic ER-positive, HER2-negative, Luminal B breast cancer who have received no prior chemotherapy for advanced or metastatic disease.

Luminal B is defined as high Ki67 (≥20%) and /or histological grade 3 and / or Luminal B according to PAM50 assay. This study will include patients irrespective of PD-L1 expression, but patients will be stratified by centrally determined PD-L1 expression. The number of patients with PD-L1 negative tumours (<1% expression) will be capped at 50% of the total study population.

Patients will be randomised (2:1) to one of the two treatment arms:

• Pembrolizumab every 3 weeks (Q3W) plus Paclitaxel on Days 1,8, and 15 every 28 days
• Paclitaxel on Days 1,8, and 15 every 28 days Paclitaxel alone

Randomisation will be stratified by the following two factors:

• Centrally assessed PD-L1 expression (<1% PD-L1 expression; ≥1%)
• Presence vs non-presence of visceral metastases

Paclitaxel treatment will be continued for at least 6 cycles unless there is evidence of unacceptable toxicity, disease progression, or if the patient requests to stop the treatment. If paclitaxel treatment is discontinued prior to disease progression, patients in the combination arm should continue pembrolizumab single agent therapy until progression or evidence of unacceptable toxicity up to a maximum of 2 years.

If disease progression is documented (RECIST 1.1) while the patient is on study medication (in the pembrolizumab plus paclitaxel arm) it would be standard practice for the patient to be taken off study medication. However, in the absence of other discontinuation criteria, patients treated with paclitaxel plus pembrolizumab may be continued on study medication if in the opinion of the treating physician there is clinical benefit. In this case patients must meet all of the following criteria:

• Evidence of clinical benefit as assessed by the investigator
• Absence of symptoms and signs (including worsening of laboratory values [e.g., new or worsening hypercalcemia]) indicating clinically significant progression of disease
• No decline in Eastern Cooperative Oncology Group (ECOG) performance status that can be attributed to disease progression
• Absence of tumour progression at critical anatomical sites (e.g., leptomeningeal disease) that cannot be managed by protocol-allowed medical interventions (i.e., pain secondary to disease or unmanageable ascites, etc.), as determined by the investigator after an integrated assessment of radiographic data, biopsy results (if available), and clinical status.

Pembrolizumab treatment will not exceed 2 years.

Patients who were randomized to the paclitaxel alone must discontinue study treatment upon determination of progressive disease. No crossover is allowed. On completion of study treatment in both arms, patients will enter a survival follow-up period during which data on cancer therapy, disease status and survival status will be collected. Endocrine maintenance therapy is not permitted prior to disease progression.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Willing and able to provide written informed consent
2. Ability to comply with the protocol
3. Female ≥ 18 years of age
4. Histologically confirmed metastatic or locally advanced breast cancer that is Luminal B, ER+ve, HER2-ve.
5. Patients must have measurable disease.
6. Representative formalin-fixed paraffin embedded breast tumour samples from the primary or recurrent cancer.
7. ECOG performance status 0-1
8. Adequate haematologic and end-organ function within 28 days prior to the first study treatment
9. Patients of childbearing potential are eligible provided they have a negative serum or urine pregnancy test on Day 1 Cycle 1 (within 72 hours) of study treatment, preferably as close to the first dose as possible.

Exclusion Criteria:

1. Luminal A breast cancer
2. Prior chemotherapy for advanced or metastatic disease
3. Prior treatment with paclitaxel in the (neo)adjuvant setting within 12 months from the end of paclitaxel treatment and randomisation into this study
4. Patients with neuropathy ≥ Grade 2
5. Previous systemic treatment for other neoplasms within 5 years prior to randomisation.
6. Patients with prior allogeneic stem cell or solid organ transplantation.
7. Prior treatment with CD137 agonists, AKT inhibitors, anti-CTLA-4, anti-OX-40, anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
8. Patients must not have a diagnosis of immunodeficiency or receiving chronic systemic steroid therapy.
9. Received therapeutic oral or intravenous antibiotics within 14 days prior to randomisation.
10. Administration of a live vaccine within 30 days prior to the first dose of study drug.
11. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL] -2) within 28days or five half-lives of the drug, whichever is shorter, prior to randomisation.
12. History of autoimmune disease.
13. History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia requiring steroids, or evidence of active pneumonitis on screening chest CT scan.
14. Active infection requiring systemic therapy.
15. History of HIV infection
16. Known active hepatitis infection.
17. Known history of active tuberculosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab + Paclitaxel; 200 mg Pembrolizumab IV Q3W plus 80 mg/m2 paclitaxel IV on Days 1,8, and 15 of each 28 day cycle.	Drug: Pembrolizumab; 200 mg Pembrolizumab IV Q3W.; Other Names: KEYTRUDA; lambrolizumab; Drug: Paclitaxel; 80 mg/m2 paclitaxel IV on Days 1,8, and 15 of each 28 day cycle.; Other Names: Taxol
Active Comparator: Paclitaxel; 80 mg/m2 paclitaxel IV on Days 1,8, and 15 of each 28 day cycle.	Drug: Paclitaxel; 80 mg/m2 paclitaxel IV on Days 1,8, and 15 of each 28 day cycle.; Other Names: Taxol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Progression-free survival, defined as the time from the date of randomisation to the date of first documented tumour progression (using RECIST 1.1) or death from any cause, whichever occurs first.	At 12months
Overall Survival	Overall Survival is defined as the time from date of randomisation to the date of death due to any cause in all patients.	At 24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of paclitaxel plus pembrolizumab versus paclitaxel through review of all AEs and SAEs assessed by CTCAE v4.03	Incidence, nature and severity of adverse events with severity determined according to CTCAE v4.03	Date of randomisation to date of all adverse event resolution following discontinuation for any reason or death, assessed up to 30 months.
Objective Response Rates	Objective Response Rate is defined as the proportion of the patients in the analysis population who have a CR or PR (using RECIST 1.1).	Date of first documentation of CR or PR or to the date of first documented tumour progression (using RECIST 1.1) or death from any cause, whichever occurs first, assessed up to 30 months.

Collaborators and Investigators

• Sponsor: Queen Mary University of London
• Collaborators: Merck Sharp & Dohme LLC; European Institute of Oncology
• Investigators: Principal Investigator: Peter Schmid, MD PhD FRCP, Queen Mary University of London

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2020
• Primary Completion (Estimated): June 1, 2023
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: February 6, 2019
• First Submitted That Met QC Criteria: February 13, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Pembrolizumab; Metastatic; Locally Advanced; Paclitaxel; PAM50; HER2-negative; ER-positive; Ki67
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Paclitaxel; Pembrolizumab
• Other Study ID Numbers: 012342QM; 2018-000188-10 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No