Study of Stereotactic Ablative Radiotherapy(SBRT) Followed by Atezolizumab / Tiragolumab in Treatment-naive Patients With Metastatic Non-small Cell Lung Cancer

Sponsor
Yonsei University
Study ID
NCT05034055
Phase
PHASE2
Status
Unknown

Conditions

Eligibility Criteria

Sex
ALL
Age
20 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • atezolizumab / tiragolumab — DRUG
    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 Details

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.

Key Dates

Start date
Dec 31, 2021
Status verified
Sep 2021
Primary completion
Dec 31, 2023
Completion
Dec 31, 2023

Study Design

Enrollment
45 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: atezolizumab / tiragolumab
    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.

Primary Outcome Measure

Progression-free survival (PFS) [ Time Frame: up to 5 years after the end of dosing ]

Central Contacts

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