A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer (Morpheus-panBC)
Breast Cancer
About this trial
This is an interventional treatment trial for Breast Cancer
Eligibility Criteria
Inclusion Criteria Stage 1
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Metastatic or inoperable locally advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)
- For the 1L PD L1+ cohort: no prior systemic treatment for metastatic or inoperable locally advanced TNBC
- For the 2L CIT-naive cohort: Eligible for capecitabine monotherapy
- For the 2L CIT-naive cohort: Radiologic/objective evidence of recurrence or disease progression after 1L treatment with chemotherapy, for a total of one line of therapy for inoperable locally advanced or metastatic breast cancer
- Life expectancy =/> 3 months, as determined by the investigator
- Tumor accessible for biopsy
- Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing
- For the 1L PD L1+ cohort: Positive PD-L1 expression, defined as >/= 1% of the tumor area occupied by PD L1-expressing tumor-infiltrating immune cells of any intensity, as determined through use of the U.S. Food and Drug Administration-approved or CE-marked Ventana PD-L1 (SP142) Assay
Inclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-naive cohort)
- Measurable disease (at least one target lesion)
- Adequate hematologic and end-organ function, laboratory test results, obtained within 14 days prior to initiation of study treatment.
- Negative HIV test at screening
- Negative hepatitis B surface antigen test
- Negative total hepatitis B core antibody (HBcAb)
- Negative hepatitis C virus (HCV) antibody test at screening
- 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
Inclusion Criteria Stage 2 (2L CIT-naive cohort)
- ECOG Performance Status of 0, 1, or 2
- Patients randomly allocated to the control arm during Stage 1: ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity, provided that Medical Monitor approval for entry into Stage 2 is obtained, or disease progression per RECIST v1.1 while receiving control treatment
- Patients randomly allocated to an experimental arm during Stage 1: ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab, disease progression per RECIST v1.1, or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment
- Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 (if deemed clinically feasible by the investigator)
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
- Treatment with investigational therapy within 28 days prior to initiation of study treatment
- 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
- 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
- Eligibility only for the control arm
Exclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-naïve cohort)
- 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
- 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
- Pregnancy or breastfeeding, or intention of becoming pregnant during the study
Exclusion Criteria for the 2L CIT-naive cohort, Stage 1
- Prior treatment with capecitabine,
- Treatment with sorivudine or its chemically related analogues, such as brivudine
- History of severe and unexpected reactions to fluoropyrimidine therapy
- Known complete absence of dihydropyrimidine dehydrogenase activity
Exclusion Criteria for Stage 2
- Inability to tolerate atezolizumab during Stage 1
- For patients receiving eribulin: congenital long QT syndrome
Additional drug-specific exclusion criteria may apply to Stage 1 and 2
Sites / Locations
- City of HopeRecruiting
- University of California San Diego Medical Center; Moores Cancer Center
- Stanford Cancer Institute
- Rocky Mountain Cancer Center - Longmont
- H. Lee Moffitt Cancer Center and Research Inst.
- Hackensack Univ Medical Center; John Theurer Cancer Ctr
- Regional Cancer Care Associates, LLC
- Rutgers Cancer Institute of New Jersey
- NYU Langone Medical Center; NYU Perlmutter Cancer Center
- Thomas Jefferson University Hospital
- University of Pittsburgh Medical Center
- The West Clinic; West Cancer CenterRecruiting
- Vanderbilt University Medical Center; Vanderbilt UniversityRecruiting
- Texas Oncology-Plano East
- Peter MacCallum Cancer Centre-East MelbourneRecruiting
- Fiona Stanley Hospital - Medical OncologyRecruiting
- Centre Léon Bérard
- Institut régional du Cancer Montpellier
- Institut Universitaire du Cancer de Toulouse-OncopoleRecruiting
- Gustave Roussy
- Universitätsklinikum Erlangen; Frauenklinik
- Universitätsklinikum Essen
- Shaare Zedek Medical Center
- Hadassah University Medical CenterRecruiting
- Rabin MC; Davidof Center - Oncology InstituteRecruiting
- Sheba Medical CenterRecruiting
- Tel-Aviv Sourasky Medical CenterRecruiting
- Seoul National University HospitalRecruiting
- Severance HospitalRecruiting
- University of Ulsan College of Medicine - Asan Medical CenterRecruiting
- Hospital del MarRecruiting
- Vall d?Hebron Institute of Oncology (VHIO), BarcelonaRecruiting
- Hospital Universitario Ramon y CajalRecruiting
- Centro Integral Oncológico Clara Campal Ensayos Clínicos STARTRecruiting
- Hospital Universitario Virgen MacarenaRecruiting
- Beatson West of Scotland Cancer Centre
- Barts Health NHS Trust - St Bartholomew's Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Active Comparator
Experimental
Experimental
Active Comparator
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Atezolizumab + Nab-Paclitaxel
Atezolizumab + Nab-Paclitaxel + Tocilizumab
Atezolizumab + Sacituzumab Govitecan
Capecitabine
Atezolizumab + Ipatasertib
Atezolizumab + SGN-LIV1A
Atezolizumab + Selicrelumab + Bevacizumab
Atezolizumab + Chemo (Gemcitabine + Carboplatin or Eribulin)
Inavolisib + Abemaciclib + Fulvestrant
Inavolisib + Ribociclib + Fulvestrant
Inavolisib (6 mg) + Trastuzumab Deruxtecan
Inavolisib (9 mg) + Trastuzumab Deruxtecan
1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab + nab-paclitaxel until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed.
1L PD-L1-positive participants will receive combination treatment with atezolizumab plus nab-paclitaxel and tocilizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed.
1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab plus sacituzumab govitecan until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed.
2L CIT-naive participants will receive capecitabine until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1). Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed.
2L CIT-naive participants will receive doublet combination treatment with atezolizumab + ipatasertib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed.
2L CIT-naive participants will receive doublet combination treatment with atezolizumab plus SGNLIV1A until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed.
2L-CIT-naive participants will receive doublet combination treatment with atezolizumab plus selicrelumab and bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed.
2L CIT-naive participants enrolled in the active comparator arm who experience disease progression per RECIST v1.1 and 2L CIT-naive participants enrolled in an experimental arm who experience loss of clinical benefit as determined by the investigator may receive doublet combination treatment with atezolizumab plus chemotherapy (gemcitabine + carboplatin or eribulin) until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed.
Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus abemaciclib plus fulvestrant until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).
Hormone receptor-positive (HR+) participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).
HER2+/HER2-low participants will receive inavolisib (6 mg) + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
HER2+/HER2-low participants will receive inavolisib (9 mg) + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.