Radiation can induce immunogenic cell death, local release of inflammatory cytokines, and damage associated molecular patterns (DAMPs) resulting in local effects on endothelial cell expression of adhesion receptors, increased immune cell trafficking, and immune cell activation. Dose, fractionation, and volume of radiation can influence immunologic effects in the tumor microenvironment. Nonclinical studies suggest that despite an initial local depletion of lymphocytes, hypofractionated regimens of radiation may be immune activating. Additionally, recent work suggests that standard fractionation and hypofractionation induce expansion of unique immune populations with standard fractionation favoring a myeloid response and hypofractionation driving a lymphoid response that may be more favorable to adaptive anti-tumor immunity. Compared to high doses of radiation, which induce immunogenic cell death, dose-dependent increases of MHC-I and death receptors, moderate fractional doses of 3-10 Gy may be optimal for activating a type I IFN response in tumor cells via a dose-dependent increase in the cytoplasmic leakage of DNA from micronuclei, which activates the cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway. Extensive experimental evidence indicates that radiotherapy can work in synergy with immunotherapy to generate T cells that reject not only the irradiated tumor but also the metastases outside of the field of irradiation, which offers a rationale for utilizing radiotherapy to enhance response to immunotherapy where tumors are unlikely to respond to immunotherapy alone.
All patients will receive 1200mg atezolizumab administered by IV infusion on Day 1 of each 21-day cycle after completion of stereotactic body radiotherapy (SBRT) for 21(+5) days. No escalations or reductions in the dose of the investigational product will be allowed.Following the administration of atezolizumab, patients will receive 600mg tiragolumab administered by IV infusion on Day 1 of each 21-day cycle. The tiragolumab dose is fixed and is not dependent on body weight.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
45
All patients will receive 1200mg atezolizumab administered by IV infusion on Day 1 of each 21-day cycle after completion of stereotactic body radiotherapy (SBRT) for 21(+5) days. No escalations or reductions in the dose of the investigational product will be allowed.Following the administration of atezolizumab, patients will receive 600mg tiragolumab administered by IV infusion on Day 1 of each 21-day cycle. The tiragolumab dose is fixed and is not dependent on body weight.
Severance Hospital, Yonsei University Health System
Seoul, South Korea
Progression-free survival (PFS)
The time from curative surgery (no disease) to recurrence/progression/death and From start of osimertinib to documented radiographic relapse/progression by RECIST 1.1 criteria
Time frame: up to 5 years after the end of dosing
Objective response rate (ORR)
according to RECIST 1.1 criteria
Time frame: Screening, After that, performed every 3 months through study completion, an average of 2 years
Overall survival (OS)
Overall survival will be followed continuously while subjects are on the study drug and every 6 months after discontinuation or progression for up to 5 years following the start of therapy either by direct contact (office visits) or via telephone contact, until death, withdrawal of study consent, or lost to follow-up.
Time frame: up to 5 years
durable clinical benefit rate
Clinical Benefit Rate (CBR) are defined as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a therapeutic intervention in clinical trials of anticancer agents.
Time frame: an average of 2 years
Adverse event or adverse experience captured
Safety
Time frame: an average of 2 years
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