A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
A Phase Ib/II, Open-label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic Breast Cancer (Morpheus-panBC)
Hoffmann-La Roche
792 participants
Mar 30, 2018
INTERVENTIONAL
Conditions
Summary
This is an umbrella study evaluating the efficacy and safety of multiple treatment combinations in participants with metastatic or inoperable locally advanced breast cancer. The study will be performed in two stages. During Stage 1, six cohorts will be enrolled in parallel in this study: Cohort 1 will consist of programmed death-ligand 1 (PD-L1)-positive participants who have received no prior systemic therapy for metastatic or inoperable locally advanced triple-negative breast cancer (TNBC) (first-line \[1L\] PD-L1+ cohort). Cohort 2 will consist of participants who had disease progression during or following 1L treatment with chemotherapy for metastatic or inoperable locally-advanced TNBC and have not received cancer immunotherapy (CIT) (second-line \[2L\] CIT-naïve cohort). Cohort 3, 5, and 6 will consist of participants with locally advanced or metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative disease with one or more PIK3CA mutations. Cohort 4 will consist of participants with locally advanced or metastatic HER2+ /HER2-low disease with one or more PIK3CA mutations who had disease progression on standard-of-care therapies (HER2+ /HER2-low cohort). In each cohort, eligible participants will initially be assigned to one of several treatment arms (Stage 1). During Stage 2, participants in the 2L CIT-naïve cohort who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment combination, provided Stage 2 is open for enrollment and all eligibility criteria are met.
Eligibility
Inclusion Criteria12
- Patients must meet all of the following criteria to qualify for Stage 1 (all cohorts) and to qualify for Stage 2 (2L CIT-naïve cohort):
- Age \>/= 18 years at the time of signing Informed Consent Form
- Eastern cooperative oncology group (ECOG) performance status of 0 or 1
- Able to comply with the study protocol, in the investigator's judgment
- Metastatic or inoperable locally advanced breast cancer
- Measurable disease (at least one target lesion) according to RECIST v1.1
- Life expectancy \>/= 3 months, as determined by the investigator
- Tumor accessible for biopsy, unless archival tissue is available
- Availability of a representative tumor specimen that is suitable for biomarker analysis via central testing
- Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from breastfeeding and donating eggs, as outlined for each specific treatment arm
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm
Exclusion Criteria19
- Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, CD40 agonists or interleukin-2 (IL-2) or IL-2-like compounds
- Biologic treatment (e.g., bevacizumab) within 2 weeks prior to initiation of study treatment, or other systemic treatment for TNBC within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
- Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study
- Eligibility only for the control arm
- Adverse events from prior anti-cancer therapy that have not resolved to Grade \</= 1 or better with the exception of alopecia of any grade and Grade \</= 2 peripheral neuropathy
- Treatment with investigational therapy within 28 days prior to initiation of study treatment
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- Uncontrolled tumor-related pain
- Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- History of leptomeningeal disease
- Active or history of autoimmune disease or immune deficiency
- 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
- Severe infection within 4 weeks prior to initiation of study treatment
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
- Significant cardiovascular disease
- Prior allogeneic stem cell or solid organ transplantation
- History of malignancy other than breast cancer within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death
- Pregnancy or breastfeeding, or intention of becoming pregnant during the study
Interventions
Capecitabine will be administered 1250 milligrams per square meter (mg/m\^2) orally twice daily on Days 1-14 of each 21-day cycle.
For Atezolizumab + SGN-LIV1A, Atezolizumab + Sacituzumab Govitecan, or Atezolizumab + Chemo arms: atezolizumab will be administered intravenously (IV), 1200 mg, on Day 1 of each 21-day cycle. For Atezolizumab + Nab-Paclitaxel, Atezolizumab + Selicrelumab + Bevacizumab, Atezolizumab + Ipatasertib, or Atezolizumab + Nab-Paclitaxel + Tocilizumab arms: atezolizumab will be administered IV, 840 mg on Days 1 and 15 of each 28-day cycle.
Ipatasertib will be administered by mouth 400 mg once a day, on Days 1-21 of each 28-day cycle.
SGN-LIV1A will be administered IV, 2.5 milligrams per kilogram (mg/kg) (maximum calculated dose 250 mg), on Day 1 of each 21-day cycle.
Bevacizumab will be administered IV, 10 mg/kg, on Days 1 and 15 of each 28-day cycle.
Gemcitabine will be administered by IV, 1000 mg/m\^2, along with carboplatin, by IV, on Days 1 and 8 of each 21-day cycle. Or Eribulin will be administered IV, 1.4 mg/m\^2 on Days 1 and 8 of each 21-day cycle.
Selicrelumab will be administered by subcutaneous (SC) injection, at a fixed dose of 16 mg on Day 1 of Cycles 1 to 4 and every third cycle thereafter (Cycle = 28 days).
Tocilizumab will be administered IV, 8 mg/kg on Day 1 of each 28-day cycle.
Nab-Paclitaxel will be administered IV, 100 mg/m\^2, on Days 1, 8, and 15 of each 28-day cycle.
Sacituzumab govitecan will be administered by IV infusion, 10 mg/kg, on Days 1 and 8 of each 21-day cycle.
Abemaciclib tablets will be administered at a dose of 150 mg twice daily by mouth on Days 1-28 of each 28-day cycle.
For Inavolisib + Abemaciclib + Fulvestrant, Inavolisib + Ribociclib (Dose #1) + Fulvestrant, Inavolisib + Ribociclib (Dose #2) + Fulvestrant, or Inavolisib + Atirmociclib + Fulvestrant arms: Fulvestrant 500 mg, administered as an IM injection on Days 1 and 15 of Cycle 1, followed by Day 1 of each 28-day cycle thereafter. For Empa + Inavolisib + Fulvestrant ± Palbociclib, or Metformin + Inavolisib + Fulvestrant ± Palbociclib arms: Fulvestrant 500 mg, administered as an IM injection on Day 1 and as per local prescribing guidelines thereafter.
Ribociclib tablets will be administered by mouth once daily.
Inavolisib tablets will be administered by mouth once daily.
Trastuzumab Deruxtecan will be administered IV, 5.4 mg/kg on Day 1 of each 21-day cycle.
Ribociclib tablets will be administered by mouth once daily.
Letrozole tablets will be administered at a dose of 2.5 mg once a day by mouth on Days 1-28 of each 28-day cycle.
Inavolisib tablets will be administered by mouth once daily.
Inavolisib tablets will be administered by mouth OD.
Empagliflozin, administered orally, once daily (QD)
For Empagliflozin + Inavolisib + Fulvestrant ± Palbociclib arm: Palbociclib 125 mg administered orally, QD in Cycle 1 followed by 125 mg on Days 1-21 of each cycle. For Metformin + Inavolisib + Fulvestrant ± Palbociclib arm: Palbociclib 125 mg administered orally, QD in Cycle 1, followed by 125 mg on Days 1-21 of each cycle (Cycle=28 days).
Metf 1000 mg administered orally QD.
Atirmociclib administered orally, BID on Days 1-28 for each 28-day cycle.
Locations(45)
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NCT03424005