advanced/metastatic soft tissu sarcoma MedDRA version: 20.0 Level: PT Classification code 10039491 Term: Sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: TECENTRIQ
Product Name: atezolizumab
Product Code: R05541267
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Concentration unit: mg/ml milligra
Sponsors
Centre Léon Bérard
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: I1.Male or female patients aged of at least : oAdult-Young Adult cohort: 12 years on day of signing informed consent. oPediatric Cohort: 6 months and maximum 11 years on day of signing informed consent. I2.Histologically-confirmed diagnosis of soft tissue sarcomas, confirmed by a pathologist from REPS network, among the 4 cohorts: oRhabdomyosarcomas (RMS), oMalign Peripheral Nerve Sheath Tumors (MPNST), oComplex genomics sarcomas including Undifferentiated Pleomorphic Sarcomas (UPS), leiomyosarcomas (LMS), Pleomorphic liposarcomas, angiosarcoma, myxofibrosarcomas oSingle genomic sarcoma including Well and de-differentiated liposarcoma, myxoid liposarcoma, synovialsarcoma, alveolar soft part sarcoma, epithelioid sarcomas, and malignant rhabdoïd tumors. I3.Availability of a representative formalin-fixed paraffin-embedded (FFPE) primary and/or metastatic tumor tissue with an associated pathology report for molecular prescreening i.e. either an archival block obtained within 6 months before ICF signature or a dedicated freshly collected de novo tumor biopsy. This tumor sample must meet the following quality/quantity control criteria: At least 20 % of tumor cells, a tumor surface area of at least 5mm2 and >90µm of depth I4.Documented MAPK pathway status and known Tumor Mutational Burden (TMB) before C1D1. I5.Previous treatment with anthracycline-based chemotherapy (in the neoadjuvant, adjuvant or metastatic setting). Note: this criteria not mandatory for pediatric rhabdomyosarcomas. I6.Previous treatment by at least one line of chemotherapy in the advanced/metastatic setting before C1D1. I7.Documented radiological disease progression as per RECIST V1.1 before C1D1. I8.At least one measurable lesion according to RECIST v1.1 before C1D1. I9.Mandatory for adult patients only - Presence of at least one tumor lesion visible by medical imaging and accessible to repeatable percutaneous sampling that permits core needle biopsy without unacceptable risk of a significant procedural complications, and suitable for retrieval of 4 cores using a 16-gauge diameter needle or larger. I10.Performance status: ?Lansky Play score for pediatric patients =65 years) yes F
Exclusion criteria
Exclusion criteria: NI1.Soft tissue sarcoma disease considered curable with surgery or radiotherapy. NI2.Prior treatment with cobimetinib or other MEK inhibitors. NI3.Prior treatment with immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, or anti-PD-L1 therapeutic antibodies. NI4.Patients with history of severe allergic or other hypersensitivity reactions to: ? Chimeric or humanized antibodies or fusion proteins, ? Biopharmaceuticals produced in Chinese hamster ovary cells, or ? Any component of the atezolizumab formulation. ? Any component of Cobimetinib formulation. NI5.History of malabsorption syndrome or other condition that would interfere with the absorption of oral medications. NI6.Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases. Note: Asymptomatic patients with treated CNS lesions are eligible, provided that all of the following criteria listed in the protocol. NI7.History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration. NI8.Left ventricular ejection fraction (LVEF) 450 ms. NI10. Patients using, or requirement to use while on the study, or not respecting the minimal wash-out period of medications listed in the protocol. NI11.Patients with a malignancy other than STS within 5 years prior to C1D1 with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated in situ carcinoma of the cervix, basal or squamous cell skin cancer, localised prostate cancer or ductal in situ carcinoma treated surgically with curative intent). NI12.History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis (see Appendix 17.3 for a more comprehensive list of pre-existing autoimmune diseases and immune deficiencies) with the following exceptions – listed in the protocol NI13.Patients with active B or C hepatitis infection. NI14.Patients with active tuberculosis. NI15.Prior allogeneic bone marrow transplantation or solid organ transplant for another malignancy in the past. NI16.History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan. NI17.Pregnant or breastfeeding women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety run in To confirm the safety of cobimetinib when combined with atezolizumab in pediatric STS patients (=6 months to 7 days despite optimal supportive care and with the following exceptions: oGrade 3 fatigue oGrade 3 endocrine disorder (thyroid, pituitary, and/or adrenal insufficiency) that is managed with or without systemic corticosteroid therapy and/or hormone replacement therapy and the patient is asymptomatic oInfusion-related reactions that resolves within 6 hours with appropriate clinical management oGrade = 3 Diarrhea adequately managed with supportive care measures. ?Any Grade 3 or Grade 4 laboratory value if: oMedical intervention is required to treat the subjects1, or oThe abnormality leads to hospitalization, or oThe abnormality persists for >1 week, or oALT or AST > 3 × ULN AND total bilirubin > 2 ×ULN 2 1: endocrinopathies that can be / are managed by substitution therapy are not considered a ST. 2: For patients with Grade 1 ALT or AST elevation at baseline as a result of liver metastases, only a Grade = 3 elevation that is also = 3 × baseline lasting > 7 days will be considered a ST. ?Any AESI ?Any other study drug related toxicity considered significant enough to be qualified as ST in the opinion of the investigators after discussion with the sponsor. Phase II : The Progression Free rate after 16 weeks of treatment (PFR16w) is defined as the rate of patients with a complete response or a partial response or a stable disease as per RECIST V1.1 at 16 weeks. ;Timepoint(s) of evaluation of this end point: safety run in : 4 weeks Phase II: 16 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •The objective response rate at 8 (16) weeks is defined as the proportion of patients with a complete response (CR) or a partial response (PR) after 8 (16) weeks of treatment. • Duration of response (DoR) is defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the date of documented progression or death in the absence of disease progression. Patients who have not progressed and who have not died at the time of analysis will be censored at the time of last tumor assessment. If no tumor assessments were performed after the date of the first occurrence of a documented CR or PR, DOR will be censored at the date of the first occurrence of a documented CR or PR plus 1 day. • Progression-free survival (PFS) is defined as the time from the first day of study treatment to the date of the first documented tumor progression or death due to any cause, whichever occurs first. Subjects who have not progressed or die at the time of analysis will be censored on the date of their last evaluable tumor assessment. The tumor-response efficacy endpoints described above will be evaluated both by investigator-assessed RECIST v1.1 (Eisenhauer et al. E J Cancer 2009, see Section 17.5 and by modified criteria for immunotherapies iRECIST (Seymour et al. Lancet Oncol 2017). • Overall survival (OS) is the time from the first day of study treatment to the date of death due to any cause. A patient who has not died will be censored at the last date known to be alive. ;Timepoint(s) of evaluation of this end point: 1 year | — |
Countries
France
Contacts
Public ContactProject manager
Centre léon bérard
Outcome results
None listed