Hoffmann-La Roche
This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with breast cancer. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the patient population. Cohort 1 will focus on participants with inoperable, locally advanced or metastatic, estrogen receptor-positive (ER+), HER2-negative breast cancer who had disease progression during or following treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i; e.g., palbociclib, ribociclib, abemaciclib) in the first- or second-line setting. Cohort 2 will focus on inoperable, locally advanced or metastatic, ER+, HER2-positive breast cancer with previous progression to standard-of-care anti-HER2 therapies, of which one was a trastuzumab-and-taxane-based systemic therapy (including in the early setting if recurrence occurred within 6 months of finishing adjuvant therapy) and one was a HER2-targeting antibody-drug conjugate (ADC; e.g., ado-trastuzumab emtansine or trastuzumab-deruxtecan) or a HER2-targeting tyrosine kinase inhibitor (TKI; e.g., tucatinib, lapatinib, pyrotinib, or neratinib). Cohort 3 will focus on inoperable, locally advanced or metastatic, ER+, HER2-negative, PIK3CA-mutated breast cancer with resistance to adjuvant endocrine therapy.
Inclusion Criteria: Inclusion Criteria for Cohort 1 (Stage 1 \[and Stage 2, only where indicated\]): * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Documented estrogen receptor-positive (ER+) tumor * Patients for whom endocrine therapy is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study, as per national or local treatment guidelines * Radiologic/objective evidence of recurrence or progression after the most recent systemic therapy for breast cancer * Disease progression during or after first- or second-line hor…
30 milligrams (mg) orally once a day (during each 28-day cycle or 21-day cycle, depending on the regimen) until unacceptable toxicity or disease progression
150 mg orally twice a day (during each 28-day cycle or 21-day cycle, depending on the regimen) until unacceptable toxicity or disease progression
400 mg orally once a day on Days 1-21 of each 28-day cycle until unacceptable toxicity or disease progression
9 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
600 mg orally once a day on Days 1-21 of each 28-day cycle until unacceptable toxicity or disease progression
10 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
360 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
On Day 1 of Cycle 1 (1 cycle is 21 days), pertuzumab and trastuzumab fixed-dose combination for subcutaneous use (PH FDC SC) will be administered SC as a fixed dose formulation of 1200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase. On Day 1 of Cycles 2 and beyond, PH FDC SC will be administered SC once every 21 days as a fixed dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase.
125 mg orally once a day on Days 1-21 during each 28-day cycle until unacceptable toxicity or disease progression
840 mg by intravenous (IV) infusion on Days 1 and 15 each 28-day cycle.