TIRAGOLUMAB for Head and neck squamous cell carcinoma (HNSCC) | dMMR/MSI-high (deficient mismatch repair) metastatic cancer | Metastatic melanoma | Locally advanced or metastatic solid tumour

Inclusion criteria

• {"criterion_text":"- Tumor lesion(s) of which a histological biopsy can be safely obtained according to standard clinical care procedures."}
• {"criterion_text":"- For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by the patient and/or partner) to use a highly effective form(s) of contraception (i.e., one that results in a low failure rate (1% per year) when used consistently and correctly."}
• {"criterion_text":"- For the head and neck squamous cell carcinoma cohort specific eligibility criteria apply • clinical T2-4a, or node positive resectable HPV-unrelated HNSCC (oral cavity, larynx, hypopharynx, p16-negative oropharynx or p16 negative unknown primary) • no evidence of distant metastases. • no previous radiotherapy to the head and neck region."}
• {"criterion_text":"- Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions should be discarded as target lesions."}
• {"criterion_text":"- Participate in the GE-269-001 CD8 investigational imaging trial provided that there are slots is that trial."}
• {"criterion_text":"- Signed informed consent."}
• {"criterion_text":"- Age ≥18 at the time of signing informed consent."}
• {"criterion_text":"- Life expectancy ≥12 weeks."}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status 0-1"}
• {"criterion_text":"- Adequate organ and bone marrow function as defined below: o Hemoglobin ≥9.0 g/dL. o Platelet count ≥100 x 109 /L. o Serum creatinine ≤1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate > 30 mL/min/1.73 m2 . A 24-hour urine creatinine collection may substitute for the calculated creatinine clearance to meet eligibility criteria. o Adequate hepatic function: ▪ Total bilirubin ≤1.5 x ULN (≤3 x ULN if liver tumor involvement); Patients with Gilbert’s syndrome do not need to meet total bilirubin requirements, provided their total bilirubin is unchanged from their baseline. Gilbert’s syndrome must be documented appropriately as past medical history. ▪ Aspartate aminotransferase (AST) ≤2.5 x ULN (≤5 x ULN if liver tumor involvement) ▪ Alanine aminotransferase (ALT) ≤2.5 x ULN (≤5 x ULN if liver tumor involvement) ▪ Alkaline phosphatase (ALP) ≤2.5 x ULN (≤5 x ULN if liver or bone tumor involvement)"}
• {"criterion_text":"- Ability to comply with the protocol."}

Exclusion criteria

• {"criterion_text":"- Signs or symptoms of infection within 2 weeks prior to atezolizumab and tiragolumab administration."}
• {"criterion_text":"- Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to cycle 1, day 1, with the exception of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for subjects with orthostatic hypotension, low-dose supplemental corticosteroids for adrenocortical insufficiency and topical steroids are allowed."}
• {"criterion_text":"- medications (e.g., a one-time dose of dexamethasone for nausea) may be allowed in the study after discussion with and approval by the principal investigator (PI)."}
• {"criterion_text":"- Brain metastases, leptomeningeal metastases."}
• {"criterion_text":"- Prior immune checkpoint inhibitor treatment, including but not limited to anti-PD1 and anti- PD-L1 antibodies (only for cohort 1, 2 and 4)."}
• {"criterion_text":"- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins."}
• {"criterion_text":"- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use atezolizumab and tiragolumab, or that may affect the interpretation of the results or render the patient at high risk from complications."}
• {"criterion_text":"- Pregnant or lactating women."}
• {"criterion_text":"- Positive test for HIV, active hepatitis B (chronic or acute defined by positive hepatitis B surface antigen (HBsAg) during screening) or hepatitis C. Patients with a medical history of hepatitis B infection (defined as a positive hepatitis B core antibody (HBcAb) and absence of an HBsAg) are eligible for this study. Patients who test positive for hepatitis C antibodies are only eligible with a negative hepatitis C RNA PCR."}
• {"criterion_text":"- Acute or chronic active EBV infection at screening EBV status should be assessed by EBV serology (e.g., anti-VCA IgM and IgG, anti-EA IgG, anti-EBNA IgG) and EBV PCR (plasma or serum). If EBV serology results indicate prior EBV infection, patients must have a negative EBV PCR (plasma or serum) to be eligible for the study."}
• {"criterion_text":"- Active tuberculosis."}
• {"criterion_text":"- Treatment with systemic immunostimulatory agents (including but not limited to IFNs, IL- 2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to the first full dose of atezolizumab and tiragolumab."}

Primary endpoints

• {"endpoint_text":"- Pathologic response of the primary tumor (pTR) in patients with HNSCC and ORR according to (i)RECIST 1.1 in patients with advanced or metastatic dMMR/MSI cancer, metastatic melanoma and patients with a locally advanced or metastatic solid tumor whom, in the opinion of the investigator, based on available clinical data, may benefit from treatment with anti-PD-L1 immunotherapy.","definition_or_measurement_approach":"Pathologic response of the primary tumor (pTR) for HNSCC; Objective response rate (ORR) measured according to (i)RECIST 1.1 as assessed by the investigator."}

Secondary endpoints

• {"endpoint_text":"- Safety assessment through: o Incidence, nature and severity of adverse events, including protocol-defined events of special interest such as described in section 10.1.6, graded according to NCI CTCAE 5.0 o Changes in laboratory test results, vital signs and physical findings.","definition_or_measurement_approach":"Safety assessed by incidence, nature and severity of adverse events graded per NCI CTCAE v5.0; changes in lab results, vital signs and physical findings."}
• {"endpoint_text":"- Assessment of DFS in patients with HNSCC. o DFS is defined as the time from surgery to the time of local, regional or distant disease recurrence or death, whichever comes first.","definition_or_measurement_approach":"Disease-free survival (DFS) defined as time from surgery to local, regional or distant recurrence or death (whichever occurs first)."}
• {"endpoint_text":"- Evaluation of ORR, PFS and DOR according to (i)RECIST, as assessed by the investigator for cohort 2, 3 and 4.","definition_or_measurement_approach":"Objective response rate (ORR), progression-free survival (PFS) and duration of response (DOR) assessed by investigator per (i)RECIST."}
• {"endpoint_text":"- The correlation between TIGIT, PD-1, PD-L1 and CD8 IHC expression on tumor tissue provided prior to start of treatment and inflammatory infiltrate with radiographic (CT or MRI) in cohort 2, 3, and pathologic response pTR in cohort 1 and 2.","definition_or_measurement_approach":"Correlation analyses between TIGIT, PD-1, PD-L1 and CD8 IHC expression (tumor tissue) and radiographic inflammatory infiltrate (CT/MRI) and pathologic response (pTR)."}

Netherlands

Earliest CTIS Part Ii Submission Date

28-10-2024

Latest Decision Or Authorization Date

04-11-2024

Processing Time Days

7

Number Of Sites

1

Number Of Participants

97

Primary sponsor

Full Name

Universitair Medisch Centrum Groningen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands