Non-small Cell Lung CancerPhase 2SKYROCKETNCT05034055
Study of Stereotactic Ablative Radiotherapy(SBRT) Followed by Atezolizumab / Tiragolumab in Treatment-naive Patients With Metastatic Non-small Cell Lung Cancer
A Phase 2 study testing atezolizumab / tiragolumab in people with Non-small Cell Lung Cancer, run by Yonsei University at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- atezolizumab / tiragolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteSouth Korea
- Study dates
- Dec 2021to Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 18Show fewer
- 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.
- Men must agree to use contraception#2 from the start of study treatment until 7 months or more after the last dose of the investigational product, or until 12 months after SBRT completion, whichever is longer.
- 1. Women of childbearing potential are defined as all women after the onset of menstruation who are not postmenopausal and have not been surgically sterilized (e.g., hysterectomy, bilateral tubal ligation, bilateral oophorectomy). Postmenopause is defined as amenorrhea for ≥12 consecutive months without specific reasons. Women using oral contraceptives, intrauterine devices, or mechanical contraception such as contraceptive barriers are regarded as having childbearing potential.
- 2. The subject must consent to use any two of the following methods of contraception: vasectomy or condom for patients who are male or female subject's partner and tubal ligation, contraceptive diaphragm, intrauterine device, spermicide, or oral contraceptive for patients who are female or male subject's partner.
Who cannot join
- 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
Show all 27Show fewer
- 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
- Uncontrollable hypertension despite appropriate treatment (e.g., systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥ 90 mmHg lasting 24 hours or more)
- Arrhythmia requiring treatment
- Patients with systemic infections requiring treatment
- Patients who have received systemic corticosteroids (except for temporary use, e.g., for examination or prophylaxis of allergic reactions) or immunosuppressants within 28 days before enrollment (exception with followings: Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study)
- Patients who have undergone surgery under general anesthesia within 28 days before enrollment
- Patients who have received radiotherapy within 28 days before enrollment, or radiotherapy to bone metastases within 14 days before enrollment
- Patients with a positive test result for any of the following: HBs antigen, or HCV antibody (except if HCV-RNA negative)
- Patients with a negative HBs antigen test but a positive test result for either HBs antibody or HBc antibody with a detectable level of HBV-DNA
- Women who are pregnant or breastfeeding, or possibly pregnant
- Patients who have received any other unapproved drug (e.g., investigational use of drugs, unapproved combined formulations, or unapproved dosage forms) within 28 days before enrollment
- Patients judged to be incapable of providing consent for reasons such as concurrent dementia
- Other patients judged by the investigator or sub-investigator to be inappropriate as subjects of this study
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Severance Hospital, Yonsei University Health System
Seoul
About this study
Official title: A Phase 2 Study of Stereotactic Ablative Radiotherapy(SBRT) Followed by Atezolizumab / Tiragolumab in Treatment-naive Patients With Metastatic Non-small Cell Lung Cancer
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.
Read the detailed description
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.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- atezolizumab / tiragolumab
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
atezolizumab / tiragolumabDrug
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: atezolizumab / tiragolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: up to 5 years after the end of dosing
Secondary outcomes (4)
Objective response rate (ORR)
according to RECIST 1.1 criteria
Measured: 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.
Measured: 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.
Measured: an average of 2 years
Adverse event or adverse experience captured
Safety
Measured: an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2021
- Study startDec 2021 (estimated)
- Primary completionDec 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Byoung Chul Byoung Chul, Principal investigator, Severance Hospital, Yonsei University Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05034055
- Sponsor's protocol ID
- 4-2021-0891
- Acronym
- SKYROCKET
- Status last verified
- Sep 2021
- First submitted
- 27 Aug 2021
- Last updated
- 5 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Stereotactic Ablative Radiotherapy(SBRT) Followed by Atezolizumab / Tiragolumab in Treatment-naive Patients With Metastatic Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT05034055
- Acronym / sponsor ID
- SKYROCKET / 4-2021-0891
- Conditions
- Non-small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- Dec 2021 (estimated)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 5 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| atezolizumab / tiragolumab | Experimental | Drug: atezolizumab / tiragolumabAll 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. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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%
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| atezolizumab / tiragolumabAll 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 |
Primary outcome
Progression-free survival (PFS)
Time frame: up to 5 years after the end of dosing
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
4 secondary outcomes
Objective response rate (ORR)
Time frame: Screening, After that, performed every 3 months through study completion, an average of 2 years
Overall survival (OS)
Time frame: up to 5 years
durable clinical benefit rate
Time frame: an average of 2 years
Adverse event or adverse experience captured
Time frame: an average of 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Byoung Chul Byoung Chul principal investigator
Severance Hospital, Yonsei University Health System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing atezolizumab / tiragolumab in people with Non-small Cell Lung Cancer, run by Yonsei University at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Byoung Chul Cho (82-2228-0880, cbc1971@yuhs.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) (time frame: up to 5 years after the end of dosing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2021.