A Study of Neoadjuvant Nivolumab + Palbociclib + Anastrozole in Post-Menopausal Women and Men With Primary Breast Cancer

NCT04075604 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CA209-7A8
• Study Type: interventional
• Target: 23
• Locations: 8 countries
• Sites: 36

Brief Summary

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

Conditions

Breast Cancer; Cancer

Keywords

Nivolumab; Breast Cancer; Cancer; ER+; HER2-; Neoadjuvant

Outcome Measures

Primary Outcomes (2)

• The Number of Participants With Dose Limiting Toxicities (DLT) in the Safety Run-in Phase

  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

  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 Outcomes (10)

• Objective Response Rate (ORR)

  From first dose up to approximately 6 months after first dose

• Breast Conserving Surgery (BCS) Rate

  From first dose up to approximately 6 months after first dose

• Pathological Complete Response (pCR) Rate

  From first dose up to approximately 6 months after first dose

• The Number of Participants Experiencing Adverse Events (AEs)

  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)

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

Study Arms (3)

Arm A: Nivolumab+Palbociclib+Anastrozole (ANZ)

EXPERIMENTAL

Biological: Nivolumab; Drug: Anastrozole; Drug: Palbociclib

Arm B: Palbociclib+ANZ then Nivolumab+Palbociclib+ANZ

EXPERIMENTAL

Biological: Nivolumab; Drug: Anastrozole; Drug: Palbociclib

Arm C: Palbociclib+ANZ

ACTIVE COMPARATOR

Drug: Anastrozole; Drug: Palbociclib

Interventions

Nivolumab BIOLOGICAL

Specified Dose on Specified Days

Arm A: Nivolumab+Palbociclib+Anastrozole (ANZ); Arm B: Palbociclib+ANZ then Nivolumab+Palbociclib+ANZ

Anastrozole DRUG

Specified Dose on Specified Days

Arm A: Nivolumab+Palbociclib+Anastrozole (ANZ); Arm B: Palbociclib+ANZ then Nivolumab+Palbociclib+ANZ; Arm C: Palbociclib+ANZ

Palbociclib DRUG

Specified Dose on Specified Days

Arm A: Nivolumab+Palbociclib+Anastrozole (ANZ); Arm B: Palbociclib+ANZ then Nivolumab+Palbociclib+ANZ; Arm C: Palbociclib+ANZ

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (36)

Local Institution - 0031

Whittier, California, 90603, United States

Location

University Cancer Blood Ctr

Athens, Georgia, 30607, United States

Location

Northside Hospital,Inc.- Central Research Department

Atlanta, Georgia, 30342, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Local Institution - 0041

Florham Park, New Jersey, 07932, United States

Location

The Cancer Center At Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

Hematology-Oncology Associates Of Fredricksburg, Inc

Fredericksburg, Virginia, 22408, United States

Location

Peninsula Cancer Institute

Newport News, Virginia, 23601, United States

Location

Local Institution - 0005

Elizabeth Vale, South Australia, 5112, Australia

Location

Breast Cancer Research Centre - WA

Nedlands, Western Australia, 6009, Australia

Location

Local Institution - 0011

Wilrijk, Antwerpen, 2610, Belgium

Location

Local Institution

Liège, 4000, Belgium

Location

Local Institution

Namur, 5000, Belgium

Location

Local Institution - 0071

Ottawa, Ontario, K1H 8L6, Canada

Location

Local Institution - 0075

Bordeaux, 33077, France

Location

Local Institution - 0073

Créteil, 94010, France

Location

Local Institution - 0072

La Roche-sur-Yon, 85925, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Local Institution - 0019

Marseille, 13273, France

Location

Centre de Cancerologie du Grand Montpellier

Montpellier, 34070, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

Local Institution

Bonn, 53111, Germany

Location

Local Institution

Erlangen, 91054, Germany

Location

Klinik Essen-Mitte

Essen, 45136, Germany

Location

Local Institution

Mönchengladbach, 41061, Germany

Location

Local Institution

Saarbrücken, 66113, Germany

Location

Local Institution - 0047

Monterrey Ponce, 00731, Puerto Rico

Location

Local Institution - 0002

San Juan, 00927, Puerto Rico

Location

Local Institution - 0062

San Juan, 00936, Puerto Rico

Location

H. Univ. Vall dHebron

Barcelona, 08035, Spain

Location

Local Institution - 0037

Barcelona, 08036, Spain

Location

Hosp Univer 12 De Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Virgen De La Victoria

Málaga, 29010, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

Hospital Clinico Universitario De Valencia

Valencia, 46010, Spain

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms

Interventions

Nivolumab; Anastrozole; palbociclib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Bristol Myers Squibb (BMS) decided to permanently discontinue enrollment and dosing in the nivolumab + abemaciclib + anastrozole cohorts during the Safety Run-in phase due to the risk of serious interstitial lung disease (ILD)/pneumonitis in patients receiving abemaciclib in combination with pembrolizumab. BMS decided to not move forward with the randomized phase of CA2097A8 and to close the trial after completion of the Safety Run-in.

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: August 29, 2019
• First Posted: September 3, 2019
• Study Start: October 18, 2019
• Primary Completion: July 27, 2021
• Study Completion: July 27, 2021
• Last Updated: August 10, 2022
• Results First Posted: August 10, 2022

Record last verified: 2022-07

Locations

AU (2); US (9); DE (5); BE (3); ES (6); FR (7); CA (1); PR (3)