A Phase II, Multicenter, Randomized, Double-Blind Study of Tobemstomig/RO7247669 Combined With Nab-Paclitaxel Compared With Pembrolizumab Combined With Nab-Paclitaxel in Participants With Previously Untreated, PD-L1-Positive, Locally-Advanced Unresectable or Metastatic Triple-Negative Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Tobemstomig
- Conditions
- Breast Cancer
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 83
- Locations
- 71
- Primary Endpoint
- Progression-Free Survival (PFS)
- Status
- Active, Not Recruiting
- Last Updated
- last month
Overview
Brief Summary
The purpose of this study is to assess the efficacy and safety of a novel immunotherapy candidate, tobemstomig, in combination with nab-paclitaxel, for patients with previously untreated, locally advanced, unresectable or metastatic (Stage IV) programmed death-ligand 1 (PD-L1)-positive triple-negative breast cancer (TNBC).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Metastatic or locally advanced unresectable, histologically documented triple-negative breast cancer (TNBC) (absence of HER2-over-expression, ER, and PgR expression by local assessment)
- •HER2-low-status
- •Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- •If metastatic disease (Stage IV), measurable disease outside of the bone
- •No prior systemic therapy for metastatic or locally advanced unresectable TNBC
- •Tumor PD-L1 expression as documented through central testing of a representative tumor tissue specimen
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Adequate hematologic and end-organ function
- •Negative HIV test at screening, with the following exception: individuals with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/uL, and have an undetectable viral load
- •Negative hepatitis B surface antigen (HBsAg) test at screening
Exclusion Criteria
- •Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 4 months after the final dose of tobemstomig or pembrolizumab, and 6 months after the final dose of nab-paclitaxel
- •Poor venous access
- •History of malignancy within 5 years prior to consent, except for the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \>90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- •History of leptomeningeal disease
- •Pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- •Hypercalcemia or hypercalcemia that is symptomatic
- •Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis (granulomatosis with polyangiitis), Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis
- •History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- •Active tuberculosis (TB)
Arms & Interventions
Arm A
Participants will receive tobemstomig every 3 weeks, plus nab-paclitaxel administered on a repeating schedule of 3 weeks on, 1 week off, until disease progression or until up to 24 months after the first treatment, whichever is sooner.
Intervention: Tobemstomig
Arm A
Participants will receive tobemstomig every 3 weeks, plus nab-paclitaxel administered on a repeating schedule of 3 weeks on, 1 week off, until disease progression or until up to 24 months after the first treatment, whichever is sooner.
Intervention: Nab-Paclitaxel
Arm B
Participants will receive pembrolizumab every 3 weeks, plus nab-paclitaxel administered on a repeating schedule of 3 weeks on, 1 week off, until disease progression or until up to 24 months after the first treatment, whichever is sooner.
Intervention: Pembrolizumab
Arm B
Participants will receive pembrolizumab every 3 weeks, plus nab-paclitaxel administered on a repeating schedule of 3 weeks on, 1 week off, until disease progression or until up to 24 months after the first treatment, whichever is sooner.
Intervention: Nab-Paclitaxel
Outcomes
Primary Outcomes
Progression-Free Survival (PFS)
Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 24 months)
Secondary Outcomes
- Objective Response Rate (ORR)(Two consecutive occasions at least 4 weeks apart (up to approximately 24 months))
- Duration of Response (DOR)(From the first occurrence of a confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 24 months))
- Overall Survival (OS)(From randomization to death from any cause (up to approximately 24 months))