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

NCT05034055 | Unknown Phase 2

• 1 other identifier: 4-2021-0891
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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

  up to 5 years after the end of dosing

Secondary Outcomes (4)

• Objective response rate (ORR)

  Screening, After that, performed every 3 months through study completion, an average of 2 years

• Overall survival (OS)

  up to 5 years

• durable clinical benefit rate

  an average of 2 years

• Adverse event or adverse experience captured

  an average of 2 years

Study Arms (1)

atezolizumab / tiragolumab

EXPERIMENTAL

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.

Drug: atezolizumab / tiragolumab

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.

atezolizumab / tiragolumab

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age (at the time of informed consent): 20 years and older
• Subjects with histologically- or cytologically-confirmed advanced or metastatic non-small cell lung cancer according to 8th edition clinical staging system of the American Joint Committee on Cancer before the start of concurrent chemoradiotherapy
• ECOG Performance Status Score 0 or 1
• Patient with no prior systemic treatment for advanced or metastatic NSCLC
• PD-L1 expression 1%
• Patients with a life expectancy of at least 3 months
• Patients with measurable disease
• Patients whose latest laboratory data meet the below criteria within 7 days before enrollment. If the date of the laboratory tests at the time of enrollment is not within 7 days before the first dose of the investigational product, testing must be repeated within 7 days before the first dose of the investigational product, and these latest laboratory tests must meet the following criteria. Of note, laboratory data will not be valid if the patient has received a granulocyte colony-stimulating factor (G-CSF) or blood transfusion within 14 days before testing.
• White blood cells ≥2,000/mm3 and neutrophils ≥1,500/mm3
• Platelets ≥100,000/mm3
• Hemoglobin ≥9.0 g/dL
• AST (GOT) and ALT (GPT) ≤3.0-fold the upper limit of normal (ULN) of the study site (or ≤5.0-fold the ULN of the study site in patients with liver metastases)
• Total bilirubin ≤1.5-fold the ULN of the study site
• Creatinine ≤1.5-fold the ULN of the study site or creatinine clearance (either the measured or estimated value using the Cockcroft-Gault equation) \>45 mL/min
• Women of childbearing potential (including women with chemical menopause or no menstruation for other medical reasons) #1 must agree to use contraception#2 from the time of informed consent until 5 months or more after the last dose of the investigational product, or until 12 months after SBRT completion, whichever is longer. Also, women must agree not to breastfeed from the time of informed consent until 5 months or more after the last dose of the investigational product, or until 12 months after SBRT completion, whichever is longer.

You may not qualify if:

• Patients with known driver oncogenes (EGFR, ALK, ROS1)
• Multiple lesions that cause RT dose beyond normal organ dose constraints
• Patients with only lesions such as pleural effusion, peritoneal seeding or leptomeningeal metastases that are not suitable for local RT
• Patients with multiple primary cancers (with the exception of completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, superficial bladder cancer, thyroid cancer or any other cancer that has not recurred for at least 5 years)
• Patients with current or past history of severe hypersensitivity to any other antibody products
• Patients with concurrent autoimmune disease or history of chronic or recurrent autoimmune disease
• Patients with a current or past history of interstitial lung disease or pulmonary fibrosis diagnosed based on imaging or clinical findings. Patients with radiation pneumonitis may be enrolled if the radiation pneumonitis has been confirmed as stable (beyond acute phase) without any concerns about recurrence.
• Patients with concurrent diverticulitis or symptomatic gastrointestinal ulcerative disease
• Patients with any metastasis in the brain or meninx that is symptomatic or requires treatment. Patients may be enrolled if the metastasis is asymptomatic and requires no treatment.
• Patients with pericardial fluid, pleural effusion, or ascites requiring treatment
• Patients who have experienced a transient ischemic attack, cerebrovascular accident, thrombosis, or thromboembolism (pulmonary arterial embolism or deep vein thrombosis) within 180 days before enrollment
• Patients with a history of uncontrollable or significant cardiovascular disease meeting any of the following criteria:
• Myocardial infarction within 180 days before enrollment
• Uncontrollable angina pectoris within 180 days before enrollment
• New York Heart Association (NYHA) Class III or IV congestive heart failure

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab; Tiragolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Byoung Chul Byoung Chul

  Severance Hospital, Yonsei University Health System

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Byoung Chul Cho

CONTACT

82-2228-0880; cbc1971@yuhs.ac

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2021
• First Posted: September 5, 2021
• Study Start: December 1, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: September 5, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)