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Stage IV NSCLCPhase 1NCT03812549

Safety and Tolerability Evaluation of Sintilimab in Combination With Radiation in Stage IV NSCLC Patients

A Phase 1 study testing Sintilimab, stereotactic body radiation therapy and Low Dose Radiotherapy in people with Stage IV NSCLC, run by Sichuan University at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This pilot phase I trial aims to investigate the safety and tolerability of anti-programmed cell death-1 (PD-1) monoclonal antibody Sintilimab (also called IBI308) in combination with concurrent stereotactic body radiation therapy (SBRT) and low dose radiotherapy (LDRT) in treating patients with stage IV non-small… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Stage IV NSCLC
What is being tested?
Sintilimab, stereotactic body radiation therapy and Low Dose Radiotherapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteChina
Study dates
18 Jan 2019to 8 Jul 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with histologically or cytologically confirmed stage IV NSCLC.
  • Enough tumor tissue samples.
  • No previous radiation, chemotherapy, immunotherapy. Patients who have received neoadjuvant or adjuvant chemotherapy 12 months before enrollment is permitted.
  • At least three measurable disease according to RECIST 1.1 that meet SBRT and LDRT radiation requirement as protocol defined
  • PD-L1 expression positive (TPS >1%)
  • Be ≥18 years of age on day of signing informed consent and ≤75 years old.
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  • ECOG 0-1.
  • Patients must have normal organ and marrow function as defined below: Total bilirubin </= 1.5 mg/dL. Aminotransferase (AST) Serum Glutamic Oxaloacetic Transaminase (SGOT)/ Alanine Aminotransferase (ALT) Serum Glutamic-Pyruvic Transaminase (SGPT) <2.5 X institutional upper limit of normal (patients with liver involvement will be allowed </= 5.0 X institutional upper normal limit) *WBC >/= 3500/uL, ANC >/= 1500/uL *Platelets >/= 90K *Hemoglobin >/= 9g/dL *Creatinine </= 1.5 x ULN.
  • Be willing and able to provide written informed consent/assent for the trial.
  • Patients should be able to tolerate a course of radiotherapy as assessed by the investigator.
  • No contradiction to radiation per radio-oncologists' judgments
  • Life expectancy of > 6 months.

Who cannot join

  • EGFR/ALK/ROS-1 mutation or mutation status unknown.
  • Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • Subjects with coronary bypass operation.
  • Subjects with insufficient heart function, liver function and kidney function.
  • Subjects with severe uncontrollable psychotic symptoms.
  • Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, anti-tumor necrosis factor agents) within 4 weeks prior to enrollment or anticipated requirement for systemic immunosuppressive medications during the trial.
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  • Subjects with active, known or suspected autoimmune disease such as interstitial pneumonia, uveitis, Crohn's disease, autoimmune thyroiditis. Subjects with cured childhood asthma, type I diabetes mellitus only requiring hormone replacement.
  • Known history of allogeneic organ or allogeneic hemopoietic stem cell transplantation.
  • Known hypersensitivity or allergy to monoclonal antibody.
  • Subjects with a history of interstitial lung disease.
  • Uncontrolled concomitant disease, including but not limited to :
  • 1)Active or poorly controlled severe infection 2)Human Immunodeficiency Virus (HIV) infection (HIV antibody positive) 3)Known acute or chronic active hepatitis B (HBV DNA positive) infection or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA positive) infection 4)Active tuberculosis 5)Symptomatic congestive heart failure (New York Heart Association grade III-IV) or symptomatic, poorly controlled arrhythmia 6)Uncontrolled hypertension (SBP ≥ 160mmHg or DBP ≥ 100mmHg) 7)Prior arterial thromboembolism event, including myocardial infarction, unstable angina, stroke and transient ischemic attack, within 6 months of enrollment 8)Concomitant disease needs anticoagulant therapy 9)Uncontrolled hypercalcemia（Ca2+>1.5mmol/L or Ca >12mg/dl or corrected Serum Calcium >ULN），or Symptomatic hypercalcemia during diphosphonate therapy
  • 12. Other primary malignancy, with the exception of: (radical Non-melanoma skin cancer or cured cervical in-situ carcinoma;).
  • 13. Subjects with other diseases or abnormal Lab test results which might increase the risk of enrollment and treatment or Interfere with the interpretation of study results could be excluded according to the judgments of investigator.
  • 14. Pregnant or lactating women.

Trial locations and contacts

1 site in 1 country.

China1 site

  • West China Hospital, Sichuan University

    Chengdu, Sichuan, 610041

Other trials in China

About this study

Official title: Multi-center Phase I Study of Sintilimab in Combination With Radiotherapy in Treatment Naive PD-L1 Positive Stage IV Non-small Cell Lung Cancer (NSCLC)

This pilot phase I trial aims to investigate the safety and tolerability of anti-programmed cell death-1 (PD-1) monoclonal antibody Sintilimab (also called IBI308) in combination with concurrent stereotactic body radiation therapy (SBRT) and low dose radiotherapy (LDRT) in treating patients with stage IV non-small cell lung cancer (NSCLC).

At least 29 participants will be enrolled in this study. All will take part at West China Hospital, Sichuan University.

Read the detailed description

This exploratory phase I study will be conducted in two steps:

Step A: A low dose radiotherapy (LDRT) dose escalation, 6 patients per cohort (a total of 18 patients) will be enrolled to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended dose for expansion (RDE) for lung LDRT.

Step B: A lung LDRT dose expansion

All eligible patients will receive lung SBRT dosed at 30 Gy in 3 fractions, in combination with LDRT at different dose levels (decried as below) starting from the 2nd day of SBRT, followed by sintilimab monotherapy starting within 7 days after radiation completed. Sintilimab will be given at 200mg every 3 weeks until disease progression, unacceptable toxicities, the patient withdraws informed consent, or sintilimab reaches a maximum of up to 24 months.

Patients in the dose escalation will receive lung LDRT at 3 cohorts with increasing dose levels: 2 Gy in 1 fraction in dose level 1, 4 Gy in 2 fractions in dose level 2, 10Gy in 5 fractions in dose level 3.

A cohort of 17 patients will receive lung LDRT at the RDE determined during the dose escalation phase in combination with SBRT and Sintilimab to obtain additional safety and response data.

Conditions
Stage IV NSCLC
Being tested
Sintilimab, stereotactic body radiation therapy, Low Dose Radiotherapy
Keywords
Immunotherapy;SBRT; PD-L1 positive; LDRT
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.

  • SintilimabDrug

    Also called IBI308

    Patients will receive treatment with Sintilimab 200mg every 3 weeks for a maximum of 24 months.

  • stereotactic body radiation therapyRadiation

    Also called SBRT

    Radiation treatment utilized in this trial consists of SBRT with a standard doses to 30 Gy/3f

  • Low Dose RadiotherapyRadiation

    Also called LDRT

    LDRT at dose escalation levels: 2 Gy/1f, 4 Gy/2f, 10 Gy/5f with conventional external beam radiation.

Study groups in NCT03812549
Study groupRoleWhat they receive
Sintilimab Combined with SBRT and LDRTExperimentalPeriod 1-Dose escalation cohort. Dose Level 1: Stereotactic body radiation therapy (SBRT) dose at 30 Gy/3f + Low Dose Radiotherapy (LDRT, 2 Gy in 1 fraction) + anti-PD-1 inhibitor 200mg. Dose Level 2: Stereotactic body radiation therapy (SBRT) dose at 30 Gy/3f + Low Dose Radiotherapy (LDRT, 4 Gy in 2 fractions) + anti-PD-1 inhibitor 200mg. Dose Level 3: Stereotactic body radiation therapy (SBRT) dose at 30 Gy/3f + Low Dose Radiotherapy (LDRT, 10 Gy in 5 fractions) + anti-PD-1 inhibitor 200mg. Period 2 - Expansion cohort. SBRT dose at 30 Gy/3f + LDRT + anti-PD-1 inhibitor 200mg, LDRT dose at RDE determined in Period 1.
Receives: Drug: Sintilimab; Radiation: stereotactic body radiation therapy; Radiation: Low Dose Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Adverse Events and/or Dose Limiting Toxicities of Sintilimab in Combination With SBRT and LDRT

    Adverse Events and/or Dose Limiting Toxicity graded per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

    Measured: from randomization through 30 days after last dosing, up to 24 months

Secondary outcomes (3)

  1. Progression Free Survival (PFS)

    Investigator assessed PFS according to RECIST v1.1. Progression free survival is defined as time of enrollment to first evidence of progressive disease.

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Measured: up to 24 months after the enrollment

  2. Objective Response Rate (ORR)

    Investigator assessed ORR using RECIST v1.1 including the all tumor, the tumor undergoing LDRT and the tumor which do not receive radiotherapy.

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

    Measured: up to 24 months after the enrollment

  3. Overall Survival (OS)

    OS is defined as the difference (in months) between the date of study enrollment to the date death due to any cause

    Measured: up to 24 months after the enrollment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2019
  2. Study start18 Jan 2019
  3. Primary completion31 Jan 2022
  4. Study completion8 Jul 2022

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03812549
Sponsor's protocol ID
IHC-001
Status last verified
Feb 2025
First submitted
18 Jan 2019
Last updated
4 Mar 2025
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015 Apr 3;348(6230):56-61. doi: 10.1126/science.aaa8172.

    PubMed 25838373

  • Demaria S, Coleman CN, Formenti SC. Radiotherapy: Changing the Game in Immunotherapy. Trends Cancer. 2016 Jun;2(6):286-294. doi: 10.1016/j.trecan.2016.05.002.

    PubMed 27774519

  • Kaur P, Asea A. Radiation-induced effects and the immune system in cancer. Front Oncol. 2012 Dec 17;2:191. doi: 10.3389/fonc.2012.00191. eCollection 2012.

    PubMed 23251903

  • Bernstein MB, Krishnan S, Hodge JW, Chang JY. Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach? Nat Rev Clin Oncol. 2016 Aug;13(8):516-24. doi: 10.1038/nrclinonc.2016.30. Epub 2016 Mar 8.

    PubMed 26951040

  • Park SS, Dong H, Liu X, Harrington SM, Krco CJ, Grams MP, Mansfield AS, Furutani KM, Olivier KR, Kwon ED. PD-1 Restrains Radiotherapy-Induced Abscopal Effect. Cancer Immunol Res. 2015 Jun;3(6):610-9. doi: 10.1158/2326-6066.CIR-14-0138. Epub 2015 Feb 19.

    PubMed 25701325

  • Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, Mu Z, Rasalan T, Adamow M, Ritter E, Sedrak C, Jungbluth AA, Chua R, Yang AS, Roman RA, Rosner S, Benson B, Allison JP, Lesokhin AM, Gnjatic S, Wolchok JD. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012 Mar 8;366(10):925-31. doi: 10.1056/NEJMoa1112824.

    PubMed 22397654

  • Du J, Su S, Li H, Shao J, Meng F, Yang M, Qian H, Zou Z, Qian X, Liu B. Low dose irradiation increases adoptive cytotoxic T lymphocyte migration in gastric cancer. Exp Ther Med. 2017 Dec;14(6):5711-5716. doi: 10.3892/etm.2017.5305. Epub 2017 Oct 13.

    PubMed 29285113

  • Brooks ED, Chang JY. Time to abandon single-site irradiation for inducing abscopal effects. Nat Rev Clin Oncol. 2019 Feb;16(2):123-135. doi: 10.1038/s41571-018-0119-7.

    PubMed 30401936

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Sintilimab, stereotactic body radiation therapy and Low Dose Radiotherapy in people with Stage IV NSCLC, run by Sichuan University at 1 site in China.

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 12 inclusion and 15 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: finished, as of the sponsor's last update on 4 Mar 2025. 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 China. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events and/or Dose Limiting Toxicities of Sintilimab in Combination With SBRT and LDRT (time frame: from randomization through 30 days after last dosing, up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03812549, which also lists 8 linked publications.

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 4 Mar 2025.

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