RecruitingRecruiting
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
NCT03424005 · Hoffmann-La Roche
In plain English
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Official title
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)
About this study
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 criteria
Inclusion Criteria
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 Criteria
Exclusion Criteria for Stage 1
* 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
Exclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-naïve cohort)
* 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
Study design
Enrollment target: 792 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2018-03-30
Estimated completion: 2030-09-30
Last updated: 2026-03-16
Interventions
Drug: CapecitabineDrug: AtezolizumabDrug: IpatasertibDrug: SGN-LIV1ADrug: BevacizumabDrug: Chemotherapy (Gemcitabine + Carboplatin or Eribulin)Drug: SelicrelumabDrug: TocilizumabDrug: Nab-PaclitaxelDrug: Sacituzumab GovitecanDrug: AbemaciclibDrug: FulvestrantDrug: Ribociclib (Dose #1)Drug: Inavolisib (Dose #1)Drug: Trastuzumab DeruxtecanDrug: Ribociclib (Dose #2)Drug: LetrozoleDrug: Inavolisib (Dose #2)Drug: InavolisibDrug: EmpagliflozinDrug: PalbociclibDrug: MetforminDrug: Atirmociclib
Primary outcomes
- • Objective Response Rate (ORR) (Baseline until disease progression or loss of clinical benefit (up to approximately 10 years))
Sponsor
Hoffmann-La Roche · industry
With: Gilead Sciences, Pfizer
Contacts & investigators
ContactReference Study ID Number: CO40115 https://forpatients.roche.com/ · contact · global-roche-genentech-trials@gene.com · 888-662-6728 (U.S. and Canada)
InvestigatorClinical Trials · study_director, Hoffmann-La Roche
All locations (45)
City of HopeCompleted
Duarte, California, United States
University of California San Diego Medical CenterCompleted
La Jolla, California, United States
Stanford Cancer InstituteWithdrawn
Stanford, California, United States
Rocky Mountain Cancer Center - LongmontCompleted
Longmont, Colorado, United States
H. Lee Moffitt Cancer Center and Research Inst.Completed
Tampa, Florida, United States
Hackensack Univ Medical CenterWithdrawn
Hackensack, New Jersey, United States
Regional Cancer Care Associates, LLCWithdrawn
Howell Township, New Jersey, United States
Rutgers Cancer Institute of New JerseyWithdrawn
New Brunswick, New Jersey, United States
NYU Langone Medical CenterWithdrawn
New York, New York, United States
Thomas Jefferson University HospitalWithdrawn
Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical CenterWithdrawn
Pittsburgh, Pennsylvania, United States
Tennessee Oncology - Chattanooga Oncology & Hematology AssociatesRecruiting
Chattanooga, Tennessee, United States
The West ClinicRecruiting
Germantown, Tennessee, United States
Tennessee Oncology PLLCRecruiting
Nashville, Tennessee, United States
Vanderbilt University Medical CenterRecruiting
Nashville, Tennessee, United States
Texas Oncology-Plano EastWithdrawn
Plano, Texas, United States
Peter MacCallum Cancer Centre-East MelbourneRecruiting
Melbourne, Victoria, Australia
Fiona Stanley Hospital - Medical OncologyRecruiting
Murdoch, Western Australia, Australia
Centre Léon BérardActive Not Recruiting
Lyon, France
Institut régional du Cancer MontpellierWithdrawn
Montpellier, France
Institut Universitaire du Cancer de Toulouse-OncopoleRecruiting
Toulouse, France
Gustave RoussyRecruiting
Villejuif, France
Universitätsklinikum ErlangenRecruiting
Erlangen, Germany
Universitätsklinikum EssenRecruiting
Essen, Germany
Rambam Medical CenterRecruiting
Haifa, Israel
Shaare Zedek Medical CenterRecruiting
Jerusalem, Israel
Hadassah University Medical CenterRecruiting
Jerusalem, Israel
Rabin MCRecruiting
Petah Tikva, Israel
Sheba Medical CenterRecruiting
Ramat Gan, Israel
Tel-Aviv Sourasky Medical CenterRecruiting
Tel Aviv, Israel
Assuta Medical CentersRecruiting
Tel Aviv, Israel
National Cancer Center Clinical Trials Center / Center for Breast CancerRecruiting
Goyang-si, South Korea
Seoul National University HospitalRecruiting
Seoul, South Korea
Severance HospitalRecruiting
Seoul, South Korea
University of Ulsan College of Medicine - Asan Medical CenterRecruiting
Seoul, South Korea
Samsung Medical CenterRecruiting
Seoul, South Korea
Hospital Universitario Virgen MacarenaRecruiting
Seville, Sevilla, Spain
Hospital del MarRecruiting
Barcelona, Spain
Vall d?Hebron Institute of Oncology (VHIO), BarcelonaRecruiting
Barcelona, Spain
Hospital Universitario Ramon y CajalRecruiting
Madrid, Spain
Centro Integral Oncológico Clara Campal Ensayos Clínicos STARTRecruiting
Madrid, Spain
National Cheng Kung University HospitalRecruiting
Tainan, Taiwan
National Taiwan University HospitalRecruiting
Taipei, Taiwan
Beatson West of Scotland Cancer CentreCompleted
Glasgow, United Kingdom
Barts Health NHS Trust - St Bartholomew's HospitalCompleted
London, United Kingdom