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

• Status: Recruiting
• Trial end date: 2024-03-20
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoffmann-La Roche
• Treatments: Antibodies; Antibodies, Monoclonal; Atezolizumab; Bevacizumab; Entinostat; Estradiol; Exemestane; Fulvestrant; Hormones; Tamoxifen

Criteria

Inclusion Criteria for Both Stages:

• 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

Inclusion Criteria for Stage 1:

• 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

Inclusion Criteria for Stage 2:

• ECOG performance status of 0-2

• Ability to initiate treatment within 3 months after disease progression or unacceptable toxicity on a Stage 1 regimen

Exclusion Criteria for Both Stages:

• 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

Exclusion Criteria for Stage 1:

• 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

Exclusion Criteria for Stage 2:

• Unacceptable toxicity with atezolizumab during Stage 1

• Uncontrolled cardiovascular disease or coagulation disorder, including use of anticoagulants as specified in the protocol

• Significant abdominal or intestinal manifestations within 6 months prior to treatment

• Grade 2 or higher proteinuria