A Study of Multiple Immunotherapy-Based Treatment Combinations in Hormone Receptor (HR)-Positive Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer

NCT03280563 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: CO396112017-000335-14
• Study Type: interventional
• Target: 144
• Locations: 3 countries
• Sites: 22

Brief Summary

This study is designed to evaluate the efficacy, safety, and pharmacokinetics of several immunotherapy-based combination treatments in participants with inoperable locally advanced or metastatic HR-positive, HER2-negative breast cancer who have progressed during or following treatment with a cyclin-dependent kinase (CDK) 4/6 inhibitor in the first- or second-line setting, such as palbociclib, ribociclib, or abemaciclib. The study will be performed in two stages. During Stage 1, participants will be randomized to fulvestrant (control) or an atezolizumab-containing doublet or triplet combination. Those who experience disease progression, loss of clinical benefit, or unacceptable toxicity may be eligible to receive a new triplet combination treatment in Stage 2 until loss of clinical benefit or unacceptable toxicity. New treatment arms may be added and/or existing treatment arms may be closed during the course of the study on the basis of ongoing clinical efficacy and safety as well as the current treatments available.

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

• Stage 1: Percentage of Participants With Objective Response

  Objective response rate (ORR) was defined as the percentage of participants with an objective response of complete response (CR) or partial response (PR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). CR was defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) that have a reduction in short axis to \< 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. Participants with missing or no response assessments were classified as non-responders. Percentages have been rounded off to the nearest whole number.

  Up to 50.4 months

Secondary Outcomes (13)

• Stage 1: Progression-free Survival (PFS)

  From randomization to the first occurrence of PD or death (up to 51.9 months)

• Stage 1: Clinical Benefit Rate (CBR)

  Up to 51.9 months

• Stage 1: Overall Survival (OS)

  From randomization to death (up to 62.2 months)

• Stage 1: Percentage of Participants Event-free for OS at Month 18

  At Month 18

• Stage 1: Duration of Response (DOR)

  From first occurrence of a documented OR to the first date of recorded PD or death (up to 50.4 months)

Study Arms (8)

Stage 1: Fulvestrant

ACTIVE COMPARATOR

Participants will receive fulvestrant until unacceptable toxicity or disease progression according to RECIST v1.1.

Drug: Fulvestrant

Stage 1: Atezolizumab + Entinostat

EXPERIMENTAL

Participants will receive doublet combination treatment with atezolizumab plus entinostat until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody; Drug: Entinostat

Stage 1: Atezolizumab + Fulvestrant

EXPERIMENTAL

Participants will receive doublet combination treatment with atezolizumab plus fulvestrant until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody; Drug: Fulvestrant

Stage 1: Atezolizumab + Ipatasertib

EXPERIMENTAL

Participants will receive doublet combination treatment with atezolizumab plus ipatasertib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Prior to enrollment into this arm, the first 6 participants in the study will complete a safety run-in with atezolizumab plus ipatasertib.

Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody; Drug: Ipatasertib

Stage 1: Atezolizumab + Ipatasertib + Fulvestrant

EXPERIMENTAL

Participants will receive triplet combination treatment with atezolizumab plus ipatasertib plus fulvestrant until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Prior to enrollment into this arm, the first 6 participants in the study will complete a safety run-in with atezolizumab plus ipatasertib.

Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody; Drug: Fulvestrant; Drug: Ipatasertib

Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy

EXPERIMENTAL

Those who progress or experience unacceptable toxicity during treatment in Stage 1 may be eligible to enter Stage 2. Participants will receive triplet combination therapy with atezolizumab plus bevacizumab plus one of three endocrine therapies (fulvestrant, exemestane, or tamoxifen) selected by the physician. Treatment in Stage 2 will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody; Drug: Bevacizumab; Drug: Exemestane; Drug: Fulvestrant; Drug: Tamoxifen

Stage 1: Mandatory On-Treatment Biopsy

EXPERIMENTAL

For experimental combination arms that demonstrate clinical activity during the preliminary phase, the Sponsor may open enrollment into a separate mandatory on-treatment biopsy cohort for that combination.

Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody; Drug: Entinostat; Drug: Fulvestrant; Drug: Ipatasertib; Drug: Abemaciclib

Stage 1: Atezolizumab + Abemaciclib + Fulvestrant

EXPERIMENTAL

Participants will receive triplet combination treatment with atezolizumab plus abemaciclib plus fulvestrant until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody; Drug: Fulvestrant; Drug: Abemaciclib

Interventions

Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody DRUG

Atezolizumab will be given as 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle. This regimen will apply to all arms except when given with entinostat in Stage 1, or exemestane or tamoxifen in Stage 2, in which atezolizumab will be given as 1200 mg via IV infusion on Day 1 of each 21-day cycle.

Also known as: Tecentriq

Stage 1: Atezolizumab + Abemaciclib + Fulvestrant; Stage 1: Atezolizumab + Entinostat; Stage 1: Atezolizumab + Fulvestrant; Stage 1: Atezolizumab + Ipatasertib; Stage 1: Atezolizumab + Ipatasertib + Fulvestrant; Stage 1: Mandatory On-Treatment Biopsy; Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy

Bevacizumab DRUG

Bevacizumab will be given as 10 milligrams per kilogram (mg/kg) via IV infusion on Days 1 and 15 of each 28-day cycle in the regimen containing fulvestrant. When given with exemestane or tamoxifen, bevacizumab will be given as 15 mg/kg via IV infusion on Day 1 of each 21-day cycle.

Also known as: Avastin

Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy

Entinostat DRUG

Entinostat will be given as 5 mg orally once a week on Days 1, 8 and 15 of each 21-day cycle.

Stage 1: Atezolizumab + Entinostat; Stage 1: Mandatory On-Treatment Biopsy

Exemestane DRUG

Exemestane will be given as 25 mg orally QD in each 21-day cycle.

Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy

Fulvestrant DRUG

Fulvestrant will be given as 500 mg intramuscularly on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycle.

Stage 1: Atezolizumab + Abemaciclib + Fulvestrant; Stage 1: Atezolizumab + Fulvestrant; Stage 1: Atezolizumab + Ipatasertib + Fulvestrant; Stage 1: Fulvestrant; Stage 1: Mandatory On-Treatment Biopsy; Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy

Ipatasertib DRUG

Ipatasertib will be given as 400 mg orally QD on Days 1-21 of each 28-day cycle.

Stage 1: Atezolizumab + Ipatasertib; Stage 1: Atezolizumab + Ipatasertib + Fulvestrant; Stage 1: Mandatory On-Treatment Biopsy

Tamoxifen DRUG

Tamoxifen will be given as 20 mg orally QD in each 21-day cycle.

Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy

Abemaciclib DRUG

Abemaciclib will be given as 150mg twice daily during each 28-day cycle.

Stage 1: Atezolizumab + Abemaciclib + Fulvestrant; Stage 1: Mandatory On-Treatment Biopsy

Eligibility Criteria

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

You may qualify if:

• Measurable disease per RECIST v1.1
• Adequate hematologic and end organ function
• Disease progression during or after first- or second-line hormonal therapy with CDK4/6 inhibitor
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Metastatic or inoperable, locally advanced, histologically or cytologically confirmed invasive HR-positive HER2-negative breast cancer
• Recommended for endocrine therapy, and cytotoxic chemotherapy not indicated at study entry
• Recurrence or progression following most recent systemic breast cancer therapy
• Disease progression during or after first- or second-line hormonal therapy for locally advanced or metastatic disease
• Postmenopausal according to protocol-defined criteria
• Life expectancy \>3 months
• Available tumor specimen for determination of PD-L1 status
• ECOG performance status of 0-2
• Ability to initiate treatment within 3 months after disease progression or unacceptable toxicity on a Stage 1 regimen

You may not qualify if:

• Significant or uncontrolled comorbid disease as specified in the protocol
• Uncontrolled tumor-related pain
• Autoimmune disease except for stable/controlled hypothyroidism, Type 1 diabetes mellitus, or certain dermatologic conditions
• Positive human immunodeficiency virus test
• Active hepatitis B or C
• Active tuberculosis
• Severe infection within 4 weeks and/or antibiotics within 2 weeks prior to study treatment
• Prior allogeneic stem cell or solid organ transplantation
• History of malignancy other than breast cancer within 2 years prior to screening except those with negligible risk of metastasis/death
• History of or known hypersensitivity to study drug or excipients
• For patients entering Stage 2, recovery from all immunotherapy-related adverse events to Grade 1 or better or to baseline at the time of consent
• Prior fulvestrant or cytotoxic chemotherapy for metastatic breast cancer, or certain other agents as specified in the protocol
• Unresolved AEs from prior anti-cancer therapy
• Eligibility only for the control arm
• Prior treatment with inhibitors as specified in the protocol

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (22)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

UCSF Helen Diller Family CCC

San Francisco, California, 94158, United States

Location

Stanford Cancer Institute

Stanford, California, 94305-5456, United States

Location

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Wellness Oncology and Hematology - Main Office

West Hills, California, 91307, United States

Location

Northwest Georgia Oncology Centers PC - Marietta

Marietta, Georgia, 30060, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Providence Cancer Center

Portland, Oregon, 97231, United States

Location

UPMC Pinnacle Health System

Harrisburg, Pennsylvania, 17102, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Univ of Pittsburgh Sch of Med

Pittsburgh, Pennsylvania, 15213, United States

Location

Sarah Cannon Research Institute / Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Rambam Medical Center

Haifa, 3109601, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

Location

Rabin Medical Center-Beilinson Campus

Petah Tikva, 4941492, Israel

Location

Sheba Medical Center

Ramat Gan, 5262100, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

National Cancer Center

Gyeonggi-do, 10408, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

University of Ulsan College of Medicine - Asan Medical Center

Seoul, 05505, South Korea

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

atezolizumab; Antibodies; Bevacizumab; entinostat; exemestane; Fulvestrant; ipatasertib; Tamoxifen; abemaciclib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2017
• First Posted: September 12, 2017
• Study Start: December 22, 2017
• Primary Completion: September 26, 2024
• Study Completion: September 26, 2024
• Last Updated: November 10, 2025
• Results First Posted: November 10, 2025

Record last verified: 2025-10

Locations

KR (3); IL (5); US (14)