A Study of Trastuzumab Emtansine in Combination With Atezolizumab or Placebo as a Treatment for Participants With Human Epidermal Growth Factor 2 (HER2)-Positive and Programmed Death-ligand 1 (PD-L1)-Positive Locally Advanced (LABC) or Metastatic Breast Cancer (MBC) (KATE3)

Roche

Status and phase: Terminated; Phase 3

Conditions: Metastatic Breast Cancer

Treatments: Drug: Atezolizumab; Other: Placebo; Drug: Trastuzumab Emtansine

Study type: Interventional

Funder types: Industry

Identifiers

NCT04740918

MO42319

2020-002818-41 (EudraCT Number)

Details and patient eligibility

About

This study will evaluate the efficacy, safety and patient-reported outcomes of trastuzumab emtansine plus atezolizumab compared with trastuzumab emtansine plus placebo in participants with HER2-positive and PD-L1-positive LABC or MBC.Participants must have progressed either during or after prior trastuzumab- (+/- pertuzumab) and taxane-based therapy for LABC/MBC; or during (or within 6 months after completing) trastuzumab- (+/-pertuzumab) and taxane-based therapy in the neoadjuvant and/or adjuvant setting.

Enrollment: 96 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• HER2+ and PD-L1+ locally advanced (LABC) or metastatic breast cancer (MBC)
• Progression must have occurred during most recent treatment for LABC/MBC or during, or within 6 months after completing, neoadjuvant and/or adjuvant therapy
• Prior treatment with trastuzumab (+/- pertuzumab) and taxane in the neoadjuvant and/or adjuvant, locally advanced, or metastatic setting
• No more than two prior lines of therapy in the metastatic setting
• Measurable disease per RESIST version 1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy >= 6 months
• Adequate hematologic and end-organ function
• For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs
• For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion criteria

• Prior treatment with trastuzumab emtansine in metastatic setting
• History of exposure to cumulative doses of anthracyclines
• Symptomatic or actively progressing central nervous system (CNS) metastases; asymptomatic CNS lesions ≤ 2cm without clinical requirement for local intervention or asymptomatic patients with treated CNS lesions are eligible
• Current Grade >= 3 peripheral neuropathy
• Cardiopulmonary dysfunction
• History of malignancy within 5 years prior to initiation of study treatment, with the exception of the cancer under investigation and malignancies with a negligible risk of metastasis or death
• History of leptomeningeal disease
• Active or history of autoimmune disease or immune deficiency
• Active hepatitis B, hepatitis C and/or tuberculosis
• Prior allogeneic stem cell or solid organ transplantation
• Receipt of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, during treatment, or within 5 months following the last dose of study treatment
• Pregnancy or lactation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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96 participants in 2 patient groups

Arm A: Trastuzumab Emtansine and Placebo

Active Comparator group

Description:

Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor.

Treatment:

Drug: Trastuzumab Emtansine

Other: Placebo

Arm B: Trastuzumab Emtansine and Atezolizumab

Experimental group

Description:

Atezolizumab 1200 mg IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor.

Treatment:

Drug: Trastuzumab Emtansine

Drug: Atezolizumab