A Study of Neoadjuvant Nivolumab + Palbociclib + Anastrozole in Post-Menopausal Women and Men With Primary Breast Cancer (CheckMate 7A8)

July 14, 2022 updated by: Bristol-Myers Squibb

Randomized, Non-comparative Neoadjuvant Phase II Study in Patients With ER+/HER2- Breast Cancer >= 2 cm With Safety Run-in, Assessing Nivolumab + Palbociclib + Anastrozole

A randomized multi-arm study evaluating the safety and efficacy of palbociclib and anastrozole with or without nivolumab in participants with ER+/HER2- breast cancer

Study Overview

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • South Australia
      • Elizabeth Vale, South Australia, Australia, 5112
        • Local Institution - 0005
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Breast Cancer Research Centre - WA
      • Liege, Belgium, 4000
        • Local Institution
      • Namur, Belgium, 5000
        • Local Institution
    • Antwerpen
      • Wilrijk, Antwerpen, Belgium, 2610
        • Local Institution - 0011
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Local Institution - 0071
      • Bordeaux, France, 33077
        • Local Institution - 0075
      • Creteil Cedex, France, 94010
        • Local Institution - 0073
      • La Roche-sur-yon Cedex 9, France, 85925
        • Local Institution - 0072
      • Lyon Cedex 08, France, 69373
        • Centre Leon Berard
      • Marseille Cedex 9, France, 13273
        • Local Institution - 0019
      • Montpellier, France, 34070
        • Centre de Cancérologie du Grand Montpellier
      • TOULOUSE Cedex 9, France, 31059
        • Institut Claudius Regaud
      • Bonn, Germany, 53111
        • Local Institution
      • Erlangen, Germany, 91054
        • Local Institution
      • Essen, Germany, 45136
        • Klinik Essen-Mitte
      • Moenchengladbach, Germany, 41061
        • Local Institution
      • Saarbruecken, Germany, 66113
        • Local Institution
      • Monterrey Ponce, Puerto Rico, 00731
        • Local Institution - 0047
      • San Juan, Puerto Rico, 00927
        • Local Institution - 0002
      • San Juan, Puerto Rico, 00936
        • Local Institution - 0062
      • Barcelona, Spain, 08035
        • H. Univ. Vall dHebron
      • Barcelona, Spain, 08036
        • Local Institution - 0037
      • Madrid, Spain, 28041
        • Hosp Univer 12 De Octubre
      • Malaga, Spain, 29010
        • Hospital Universitario Virgen de la Victoria
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocío
      • Valencia, Spain, 46010
        • Hospital Clinico Universitario de Valencia
    • California
      • Whittier, California, United States, 90603
        • Local Institution - 0031
    • Georgia
      • Athens, Georgia, United States, 30607
        • University Cancer Blood Ctr
      • Atlanta, Georgia, United States, 30342
        • Northside Hospital,Inc.- Central Research Department
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • New Jersey
      • Florham Park, New Jersey, United States, 07932
        • Local Institution - 0041
      • Hackensack, New Jersey, United States, 07601
        • The Cancer Center at Hackensack University Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44109
        • MetroHealth Medical Center
    • Virginia
      • Fredericksburg, Virginia, United States, 22408
        • Hematology-Oncology Associates Of Fredricksburg, Inc
      • Newport News, Virginia, United States, 23601
        • Peninsula Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

  • Participants must have untreated, unilateral, histologically confirmed ER+, HER2- invasive breast cancer with primary tumor ≥2 cm in largest diameter (cT1-3) in one dimension by clinical or radiographic exam, for whom neoadjuvant endocrine monotherapy deemed to be a suitable therapy.
  • Participants must be deemed eligible for surgery and must agree to undergo surgery after completion of neoadjuvant therapy and agree to provide tumor tissue at baseline, on-treatment, and at surgery.
  • Women must have documented proof that they are not of childbearing potential.
  • Participants must have a performance status (PS) ≤ 1 on the Eastern Cooperative Oncology Group (ECOG) scale

Exclusion Criteria:

  • Participants who may have had any treatment, including radiotherapy, chemotherapy, and/or targeted therapy administered for the currently diagnosed breast cancer prior to enrollment or for whom upfront chemotherapy is clinically judged appropriate as optimal neoadjuvant treatment.
  • Participants who have a history of or active, known or suspected autoimmune disease, or other syndrome that requires systemic steroids above physiological replacement dose or autoimmune agents for the past 2 years.
  • Prior treatment with either ET or CDK4/6 inhibitors for Breast Cancer (BC) within 5 years or an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways, or history of allergy, or hypersensitivity to study drug components
  • Prior malignancy active within the previous 3 years or participants with serious or uncontrolled medical disorders.
  • Personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), long or short QT syndrome, Brugada syndrome, or known history of corrected QT prolongation, Torsade de Pointes, or sudden cardiac arrest.

Other protocol-defined inclusion/exclusion criteria apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: Nivolumab+Palbociclib+Anastrozole (ANZ)
Specified Dose on Specified Days
Specified Dose on Specified Days
Specified Dose on Specified Days
Experimental: Arm B: Palbociclib+ANZ then Nivolumab+Palbociclib+ANZ
Specified Dose on Specified Days
Specified Dose on Specified Days
Specified Dose on Specified Days
Active Comparator: Arm C: Palbociclib+ANZ
Specified Dose on Specified Days
Specified Dose on Specified Days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Number of Participants With Dose Limiting Toxicities (DLT) in the Safety Run-in Phase
Time Frame: From first dose to 4 weeks after first dose
The number of participants with dose limiting toxicities (DLTs) during the safety run-in phase. DLTS are defined as treatment emergent adverse events (TEAE) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 that occurs during the first 4 weeks (1 cycle) after treatment. Participants who withdraw from the study during the DLT evaluation period or have received less than 1 dose of nivolumab and 75% of accumulative doses of palbociclib of the cycle for reasons other than a DLT will not be considered as DLT-evaluable participants.
From first dose to 4 weeks after first dose
Residual Cancer Burden (RCB) 0-1 Rate in the Randomized Phase
Time Frame: From randomization phase up to 5 treatment cycles (up to approximately 20 weeks)

RCB 0-I rate is defined as the percentage of randomized participants who achieve RCB 0: no residual disease or RCB-I: minimal residual disease. RCB is a continuous index combining pathological measurements of primary tumor (size and cellularity) and nodal metastases (number and size) defined by a point system at surgery.

No participants continued to the randomized phase; trial was closed after completion of the Safety Run-in.

From randomization phase up to 5 treatment cycles (up to approximately 20 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: From first dose up to approximately 6 months after first dose
ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per investigator radiographic assessment. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
From first dose up to approximately 6 months after first dose
Breast Conserving Surgery (BCS) Rate
Time Frame: From first dose up to approximately 6 months after first dose
The percentage of participants who undergo breast conserving surgery (BCS) after completing the study treatments. Confidence interval based on the Clopper and Pearson method.
From first dose up to approximately 6 months after first dose
Pathological Complete Response (pCR) Rate
Time Frame: From first dose up to approximately 6 months after first dose
The percentage of participants with an absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy. Confidence interval based on the Clopper and Pearson method.
From first dose up to approximately 6 months after first dose
The Number of Participants Experiencing Adverse Events (AEs)
Time Frame: From first dose to 30 days after last dose of study therapy (up to approximately 6 months)
The number of participants experiencing adverse events (AEs). An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
From first dose to 30 days after last dose of study therapy (up to approximately 6 months)
The Number of Participants Experiencing Serious Adverse Events (SAEs)
Time Frame: From first dose to 30 days after last dose of study therapy (up to approximately 6 months)
The number of participants experiencing serious adverse events (SAEs). A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
From first dose to 30 days after last dose of study therapy (up to approximately 6 months)
The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
Time Frame: From first dose to 30 days after last dose of study therapy (up to approximately 6 months)
The number of participants experiencing adverse events (AEs) that lead to discontinuation of study treatment. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
From first dose to 30 days after last dose of study therapy (up to approximately 6 months)
The Number of Participants Experiencing Immune-Related Adverse Events (AEs)
Time Frame: From first dose to 100 days after last dose of study therapy (up to approximately 8 months)
The number of participants experiencing adverse events that are immune-related. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
From first dose to 100 days after last dose of study therapy (up to approximately 8 months)
The Number of Participants Deaths
Time Frame: From first dose up to approximately 8 months
The number of participants that have died during the study.
From first dose up to approximately 8 months
The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests - SI Units
Time Frame: From first dose to 30 days after last dose of study therapy (up to approximately 6 months)

The number of participants with laboratory abnormalities in specific thyroid tests based on SI conventional units.

TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal

From first dose to 30 days after last dose of study therapy (up to approximately 6 months)
The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests
Time Frame: From first dose to 30 days after last dose of study therapy (up to approximately 6 months)

The number of participants with laboratory abnormalities in specific liver tests based on SI conventional units.

ALT = Alanine Aminotransferase AST = Aspartate Aminotransferase ULN = Upper Limit of Normal

From first dose to 30 days after last dose of study therapy (up to approximately 6 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 18, 2019

Primary Completion (Actual)

July 27, 2021

Study Completion (Actual)

July 27, 2021

Study Registration Dates

First Submitted

August 29, 2019

First Submitted That Met QC Criteria

August 29, 2019

First Posted (Actual)

September 3, 2019

Study Record Updates

Last Update Posted (Actual)

August 10, 2022

Last Update Submitted That Met QC Criteria

July 14, 2022

Last Verified

July 1, 2022

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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