A Study of the Efficacy and Safety of Trastuzumab Emtansine in Combination with Atezolizumab or Placebo in Patients with HER2-Positive and PD-L1-Positive Locally Advanced or Metastatic Breast Cancer who Have Received Prior Trastuzumab- (+/- Pertuzumab) and Taxane-Based Therapy (KATE3).

Phase 1

• Conditions: ocally advanced / metastatic breast cancer; MedDRA version: 21.1Level: LLTClassification code 10072740Term: Locally advanced breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]; MedDRA version: 23.0Level: PTClassification code 10065430Term: HER2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2020-002818-41-PT
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-01-22
• Last Update Posted: 26 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 350

Inclusion Criteria

• Age >= 18 years
• Histologically determined HER2+/PD-L1+ LABC or MBC that is unresectable and who have received prior trastuzumab- (+/- pertuzumab) and taxane-based therapy
• Measurable disease per RESIST version 1.1
• Histologically centrally determined HER2+ and PD-L1+ of representative tumor tissue specimen(s) prior to randomization
• For patients with bilateral breast cancer, HER2 positivity must be centrally determined preferably in a metastatic biopsy or if not available in primary tumor from both left and right breast; at least one biopsy must be centrally determined as PD-L1 positive
• A formalin-fixed paraffin-embedded tumor specimen in a paraffin block or at least 17 slides containing unstained, freshly cut, serial sections must be submitted prior to study enrollment
• Willing to provide blood samples before treatment start, while on-study, and at progression, for standard of care follow-up and exploratory research on biomarkers
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Life expectancy >= 6 months
• Adequate hematologic and end-organ function
• Negative HIV test at screening
• For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs during the treatment period and for 7 months after the final dose of study treatment
• For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for 7 months after the final dose of study treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to Cycle 1, Day 1
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
• Receipt of any anti-cancer drug/biologic or investigational treatment 21 days prior to Cycle 1, Day 1 except hormone therapy, which can be given up to 7 days prior to Cycle 1, Day 1; recovery of treatment-related toxicity consistent with other eligibility criteria
• Prior treatment with trastuzumab emtansine in metastatic setting
• History of exposure to protocol defined cumulative doses of anthracyclines
• Symptomatic or actively progressing central nervous system metastases; asymptomatic CNS lesions = 2cm without clinical requirement for local intervention or asymptomatic patients with treated CNS lesions are eligible after fulfillment more detailed requirements of the protocol
• History of leptomeningeal disease
• Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to randomization
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Uncontrolled or symptomatic hypercalcemia
• Current Grade >= 3 peripheral neuropathy (according to the NCI CTCAE v5.0)
• Active hepatitis B and hepatitis C
• Current treatment with anti-viral therapy for HBV
• Active or history of autoimmune disease or immune deficiency
• Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• Active tuberculosis
• Cardiopulmonary dysfunction
• Major surgical procedure, other than for diagnosis, or significant traumatic injury within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
• History of malignancy within 5 years prior to initiation of study treatment, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death
• Current severe, uncontrolled systemic disease
• Prior allogeneic stem cell or solid organ transplantation
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of study treatment
• Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humaniz

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate superiority of the experimental over the control treatment with respect to progression-free survival (PFS) and overall survival (OS). ;Secondary Objective: • To evaluate the efficacy of trastuzumab emtansine plus atezolizumab compared with trastuzumab emtansine plus placebo beyond PFS and OS;<br>• To evaluate the safety of trastuzumab emtansine plus atezolizumab compared with trastuzumab emtansine plus placebo;<br>• To characterize the pharmacokinetics (PK) of trastuzumab emtansine and atezolizumab when given in combination;<br>• To evaluate the immune response to atezolizumab and trastuzumab emtansine when given in combination. <br>;Primary end point(s): 1. Progression-free survival (investigator assessed)<br>2. Overall survival<br>;Timepoint(s) of evaluation of this end point: 1-2. Up to 78.1 months.