A Study to Evaluate Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients with Metastatic Triple-Negative Breast Cancer (MORPHEUS-TNBC)
- Conditions
- Triple-negative breast cancer (TNBC)MedDRA version: 20.0Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-002038-21-ES
- Lead Sponsor
- F. Hoffman-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 110
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Metastatic or locally advanced, histologically documented TNBC
- Eligible for capecitabine monotherapy
- Radiologic/objective evidence of recurrence or disease progression after one line of chemotherapy (chemo) for metastatic breast cancer
- Life expectancy>= 3 months
- Availability of a representative tumor specimen that is suitable for determination of Programmed death-ligand 1and/or additional biomarker status via central testing
Stage 1 and Stage 2
- Measurable disease according to Response Evaluation Criteria in Solid Tumors 1.1
- Tumor accessible for biopsy
- Adequate hematologic and end-organ function
- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen during the 14 days prior to initiation of study treatment
- Negative HIV test, hepatitis B surface antigen at screening, and hepatitis C virus (HCV) antibody test or positive HCV antibody test followed by a negative HCV RNA test at screening
- For women of childbearing potential: agreement to remain abstinent or use treatment arm-specific contraceptive measures
- For men: agreement to remain abstinent or use treatment arm-specific contraceptive measures, and agreement to refrain from donating sperm for a treatment arm-specific time period
Stage 2
- 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 (Atezo), 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50
Stage 1
-Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti- cytotoxic T lymphocyte-associated molecule-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
-Treatment with investigational therapy within 28 days prior to initiation of study treatment , sorivudine or its chemically related analogues and systemic treatment for TNBC within 2 weeks (wks) of Cycle (C)1, Day(D)1 or 5 half-lives of the drug prior to C1,D1
-Adverse events from prior anti-cancer therapy that have not resolved to Grade<=1 or better with the exception of alopecia of any grade,Grade <= 2 peripheral neuropathy
-History of severe and unexpected reactions to fluoropyrimidine therapy
-Known complete absence of dihydropyrimidine dehydrogenase activity
Stage 1 and 2
-Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, tumor-related pain and uncontrolled or symptomatic hypercalcemia
-Symptomatic, untreated, or actively progressing central nervous system metastases
-History of leptomeningeal disease, idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan and malignancy other than breast cancer within 2 years prior to screening and history of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins and active or history of autoimmune disease or immune deficiency
-Active tuberculosis and significant cardiovascular disease
-Grade >= 3 hemorrhage or bleeding event within 28 days prior to initiation of study treatment
-Prior allogeneic stem cell or solid organ transplantation
-Treatment with a live, attenuated vaccine within 4wks prior to initiation of study treatment, or anticipation of need for such a vaccine during treatment with atezo or within 5 months after the last dose of atezo
-Known hypersensitivity to Chinese hamster ovary cell products or recombinant human antibodies
-Treatment with systemic immunostimulatory agents and immunosuppressive medication within 4wks or 5 half-lives of the drug prior to initiation of study treatment and within 2wks prior to initiation of study treatment respectively
Atezo+Ipatasertib (Ipat) (Stage 1)
-Grade >= 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceremia
-History of Type I or II diabetes mellitus requiring insulin and history or presence of an abnormal electrocardiogram
-Congenital long QT syndrome or screening QT interval corrected through use of Fridericia’s formula > 480ms
-Treatment with strong CYP3A4 inducers within 4wks or 5 drug-elimination half-lives prior to initiation of study drug
Atezo+SGN-LIV1A (Stage 1)
-Prior treatment with SGN-LIV1A or prior treatment with a monomethyl auristatin E -based biologic
-Grade>= 2 neuropathy
-Known hypersensitivity to any excipient contained in the drug formulation of SGN-LIV1A
-Radiotherapy within 2wks prior to first dose of study drug
-Documented history of a cerebrovascular event, unstable angina, myocardial infarction, or cardiac symptoms consistent with congestive heart failure, Class III-IV, by New York Heart Association criteria within 6 months prior to study enrollment
Atezo+ Bevacizumab (Bev) (Stage 1)
-Inadequately controlled arterial hypertension based on an average of >= 3BP readings on >=2 sessions
-Prior history of hypertensive crisis or hypertensive encephalopathy
-Significant vascular disease
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method