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Lung NeoplasmsPhase 3NCT03607539

Efficacy and Safety Evaluation of Sintilimab in Patients With Advanced or Metastatic Non-squamous NSCLC

A Phase 3 study testing Sintilimab, Pemetrexed and Platinum in people with Lung Neoplasms, run by Innovent Biologics (Suzhou) Co. Ltd. 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
Search all trials

Trial summary

Efficacy and Safety Evaluation of IBI308 in Patients with advanced or metastatic Non-squamous NSCLC Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Lung Neoplasms
What is being tested?
Sintilimab, Pemetrexed and Platinum
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
397 participants
Where
1 siteChina
Study dates
23 Aug 2018to 31 May 2022
Phase
Phase 3
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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Sign written informed consent before any trial-related processes are implemented;
  • Age ≥ 18 years and <75 years;
  • Life expectancy exceeds 3 months;
  • The investigator confirmed at least one measurable lesion according to RECIST 1.1.
  • A measurable lesion located in the field of previous radiation therapy or after local treatment may be selected as a target lesion if it is confirmed to have progressed;
  • According to the International Lung Cancer Research Association and the American Association for the Classification of Cancer Classification, the 8th edition of the TNM (Tumor Node Metastasis) staging of lung cancer, a histologically or cytologically confirmed locally advanced (IIIB/IIIC phase) that cannot be treated surgically and cannot undergo radical concurrent chemoradiotherapy, Patients with metastatic or recurrent (stage IV) non-squamous NSCLC;
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  • Confirmed for patients with EGFR (Epidermal growth factor receptor) or ALK (Anaplastic lymphoma kinase) targeted therapy (documentary evidence of no tumor EGFR-sensitive mutations and no ALK gene rearrangement)
  • The Eastern Cancer Cooperative Group (ECOG) has a performance score of 0 or 1;
  • Have not received any systematic anti-tumor treatment for advanced disease; The patient may have received adjuvant chemotherapy as long as the disease relapses at least 6 months after the last dose of chemotherapy is completed;
  • Adequate hematologic function, defined as absolute neutrophil count ≥1.5×10^9 /L, platelet count ≥100 ×10^9 /L, hemoglobin ≥9g/dL (no blood transfusion or erythropoietin (EPO) within 7 days) Dependency);
  • Adequate liver function, defined as total bilirubin levels ≤ 1.5 times normal upper limit (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times ULN in all patients, or for recorded liver Patients with metastasis, AST and ALT levels ≤ 5 times ULN;
  • Adequate renal function, defined as serum creatinine ≤ 1.5 times ULN or measured or calculated creatinine clearance ≥ 60 ml / min (Cockcroft-Gault formula);
  • Coagulation function is adequate, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times normal upper limit (ULN); if the subject is receiving anticoagulant therapy, as long as the PT is used in anticoagulant drugs Within the scope;
  • Female subjects of childbearing age should be negative for urine or serum pregnancy test within 72 hours prior to the first study drug administration (Day 1, Day 1). If the urine pregnancy test results are positive or cannot be confirmed as negative, a blood pregnancy test is required.
  • If there is a risk of conception, male and female patients are required to use high-efficiency contraception (ie, an annual failure rate of less than 1%) and continue until at least 180 days after stopping the trial treatment; Note: If abstinence is the usual lifestyle of the subject and the preferred method of contraception, abstinence can be accepted as a method of contraception.

Who cannot join

  • Histological squamous cell-dominated NSCLC; Mixed cell types must distinguish between dominant cell morphology, and if small cell types are present, the subject is not eligible for inclusion;
  • Currently participating in interventional clinical research or treatment, or receiving other research drugs or using research equipment within 4 weeks before the first dose;
  • Previously received the following therapies: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or against another stimulatory or synergistic inhibition of T cell receptors [eg CTLA-4 (Cytotoxic T lymphocyte antigen-4), OX-40 (also called CD134, cluster of differentiation134), CD137] agent;
  • Received a traditional Chinese medicine with anti-tumor effect, or an immunomodulatory drug (thymosin, interferon, interleukin) within 2 weeks before the first dose, or received major surgery within 3 weeks before the first dose;
  • Pulmonary radiation therapy of >30 Gy within 6 months prior to the first dose;
  • Completed palliative radiotherapy within 7 days prior to the first dose;
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  • Clinical active diverticulitis, abdominal abscess, gastrointestinal obstruction and peritoneal metastasis;
  • Have received a physical organ or blood system transplant;
  • There is clinically uncontrollable pleural effusion/peritoneal effusion;
  • known to have severe allergic reactions (≥3 grade) to the active ingredients of Sintilimab, pemetrexed, cisplatin, carboplatin and or any excipients;
  • Active autoimmune diseases requiring systemic treatment (eg, using a disease-modifying drug, corticosteroid or immunosuppressant) within 2 years prior to the first dose. Alternative therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic treatments;
  • Diagnosis of immunodeficiency or study of systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study.
  • Physiological doses of corticosteroids (≤10 mg/day of prednisone or equivalent) are permitted;
  • Has not fully recovered from the toxicity and/or complications caused by any intervention before starting treatment (ie, ≤1 or reaching baseline, excluding fatigue or alopecia);
  • Other malignant tumors were diagnosed within 5 years prior to the first dose, with the exception of radical cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, and/or radically resected carcinoma in situ;
  • Active central nervous system (CNS) metastasis and / or cancerous meningitis. Patients with treated brain metastases who have remained clinically stable for at least 2 weeks and have no new or advanced brain metastases may be enrolled and discontinued hormone therapy 3 days prior to the first study drug. Patients with known untreated, asymptomatic brain metastases can be enrolled, but regular imaging assessments of the brain must be performed.
  • There is a history of (non-infectious) pneumonia requiring steroid therapy or the presence of interstitial lung disease 1 year before the first dose;
  • There are active infections that require systemic treatment;
  • Subjects who are unable or unwilling to receive folic acid or vitamin B12 supplementation;
  • There are known cases of mental illness or substance abuse that may have an impact on compliance with the test requirements;
  • A history of human immunodeficiency virus (HIV) infection (ie, HIV 1/2 antibody positive) is known.
  • Untreated active hepatitis B;
  • Note: Controlled (treated) hepatitis B subjects also meet the inclusion criteria if the following criteria are met:
  • At least 4 weeks of HBV (Hepatitis B virus) antiviral therapy must have been received prior to the first dose of study drug, and the HBV viral load is <1000 copies/ml (200 IU/ml). Subjects who are receiving HBV therapy and have a viral load of <1000 copies/ml (200 IU/ml) should receive antiviral therapy throughout the study treatment period.
  • For subjects with anti-HBc (hepatitis B core antigen)(+), HBsAg(-), anti-HBs(-), and HBV viral load (-), prophylactic anti-HBV therapy is not required, but viral reactivation is closely monitored;
  • Active HCV (Hepatitis C virus)-infected subjects (HCV antibody positive and HCV-RNA levels above the lower limit of detection);
  • Vaccination of live vaccine within 30 days before the first dose (1st cycle, 1st day); Note: Inactivated virus vaccines for seasonal influenza, injectable drugs are permitted; however, live attenuated influenza vaccines (such as FluMist®) are not allowed for intranasal administration;
  • There may be a history of illness or disease evidence, treatment or laboratory abnormalities that may interfere with the subject's full participation in the study, or the investigator believes that participating in the study is not in the best interests of the subject, including dialysis.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Sun Yat-Sen University Cancer Center

    Guangzhou

Other trials in China

About this study

Official title: A Randomized, Double-blinded, Phase III Study of Pemetrexed Plus Platinum Chemotherapy With or Without Sintilimab (IBI308) in First Line Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Subjects (Orient-11)

Efficacy and Safety Evaluation of IBI308 in Patients with advanced or metastatic Non-squamous NSCLC

Read the detailed description

Sintilimab is expected to increase the PFS from 6 months to 9.2 months. Anti-PD-1 therapy in Chinese non-squamous NSCLC naïve patients will be investigated in this clinical trial.

Additionally the correlation between PD-L1 expression and the response to Sintilimab treatment in Chinese non-squamous NSCLC as well as the role of iRECIST in immune checkpoint inhibitor treatment evaluation will also be assessed.

Conditions
Lung Neoplasms
Being tested
Sintilimab, Pemetrexed, Platinum, Placebos
Medical subject headings
Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SintilimabDrug

    Also called IBI308

    10 mL:100 mg，200mg，Q3W (qualer 3 weeks), day1, I.V.

  • PemetrexedDrug

    500mg/m^2; Q3W (qualer 3 weeks), day1, I.V.

  • PlatinumDrug

    Q3W (qualer 3 weeks), day1, I.V.; first 4 cycles.

  • PlacebosDrug

    10 mL:100 mg，200mg，Q3W (qualer 3 weeks), day1, I.V.

Study groups in NCT03607539
Study groupRoleWhat they receive
Sintilimab in combination with pemetrexed and platinumExperimentalInjection; dosage form: 10ml: 100mg; frequency: 200mgQ3W (qualer 3 weeks); duration: randomization to the date of the first documented tumor progression per RECIST v1.1 criteria Sintilimab 200mg + pemetrexed/ platinum 4 cycles then Sintilimab 200mg + pemetrexed maintains
Receives: Drug: Sintilimab; Drug: Pemetrexed; Drug: Platinum
Sitilimab Placebo ComparatorPlacebo comparatorplacebo 2 vials + pemetrexed/ platinum 4 cycles then Sintilimab 200mg + pemetrexed maintains
Receives: Drug: Pemetrexed; Drug: Platinum; Drug: Placebos

What is being measured

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

  1. Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Independent Radiographic Review Committee (IRRC)

    PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD

    Measured: Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)

Secondary outcomes (5)

  1. Overall Survival (OS)

    The analysis population consisted of all randomized participants.

    Measured: Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)

  2. Objective Response Rate (ORR) by IRRC Assessment

    ORR was defined as the percentage of participants in the analysis population who had a confirmed CR (disappearance of all lesions) or PR (at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) according to RECIST 1.1, which was modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a confirmed CR or PR according to RECIST 1.1 as assessed by IRC was reported as the ORR

    Measured: Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)

  3. Disease Control Rate (DCR) by IRRC Assessment

    Measured: Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)

  4. Time to Response (TTR) by IRRC Assessment

    TTR was defined as the time of participants from the first treatment administration to the first incidence of a confirmed CR (disappearance of all lesions) or PR (at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) according to RECIST 1.1, which was modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The time from first treatment administration to the first incidence of treatment response was reported as the TTR

    Measured: Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)

  5. Duration of Response (DOR) by IRRC Assessment

    Measured: From time of first documented evidence of CR or PR trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)

Timeline

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

  1. First posted31 Jul 2018
  2. Study start23 Aug 2018
  3. Primary completion15 Nov 2019
  4. Study completion31 May 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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
397 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03607539
Sponsor's protocol ID
CIBI308C302
Status last verified
Feb 2023
First submitted
12 Jul 2018
Last updated
11 May 2026
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Liu T, He J, Wang Y, Yang Y, Zhang L, Shi M, Liu J, Sun D, Wang Z, Fang J, Yu Q, Han B, Cang S, Chen G, Mei X, Yang Z, Huang Y, Fang W, Yang Y, Zhao Y, Zhang L. Health-related quality of life and symptoms in patients with previously untreated, locally advanced or metastatic non-squamous non-small cell lung cancer treated with sintilimab or placebo plus pemetrexed and platinum (ORIENT-11): A randomized, double-blind, phase 3 trial. Lung Cancer. 2025 Feb;200:108108. doi: 10.1016/j.lungcan.2025.108108. Epub 2025 Jan 27.

    PubMed 39884222

  • Liu Z, Yao Y, Zhao M, Zhao Q, Xue J, Huang Y, Qin S. Radiomics Models Derived From Arterial-Phase-Enhanced CT Reliably Predict Both PD-L1 Expression and Immunotherapy Prognosis in Non-small Cell Lung Cancer: A Retrospective, Multicenter Cohort Study. Acad Radiol. 2025 Jan;32(1):493-505. doi: 10.1016/j.acra.2024.07.028. Epub 2024 Jul 31.

    PubMed 39084935

  • Zhang L, Wang Z, Fang J, Yu Q, Han B, Cang S, Chen G, Mei X, Yang Z, Stefaniak V, Lin Y, Wang S, Zhang W, Sun L, Yang Y. Final overall survival data of sintilimab plus pemetrexed and platinum as First-Line treatment for locally advanced or metastatic nonsquamous NSCLC in the Phase 3 ORIENT-11 study. Lung Cancer. 2022 Sep;171:56-60. doi: 10.1016/j.lungcan.2022.07.013. Epub 2022 Jul 19.

    PubMed 35917647

  • Yang Y, Wang Z, Fang J, Yu Q, Han B, Cang S, Chen G, Mei X, Yang Z, Ma R, Bi M, Ren X, Zhou J, Li B, Song Y, Feng J, Li J, He Z, Zhou R, Li W, Lu Y, Wang Y, Wang L, Yang N, Zhang Y, Yu Z, Zhao Y, Xie C, Cheng Y, Zhou H, Wang S, Zhu D, Zhang W, Zhang L. Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11). J Thorac Oncol. 2020 Oct;15(10):1636-1646. doi: 10.1016/j.jtho.2020.07.014. Epub 2020 Aug 8.

    PubMed 32781263

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sintilimab, Pemetrexed and Platinum in people with Lung Neoplasms, run by Innovent Biologics (Suzhou) Co. Ltd. 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 15 inclusion and 28 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 11 May 2026. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 16 Feb 2021). 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?

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Independent Radiographic Review Committee (IRRC) (time frame: Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 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 NCT03607539, which also lists 4 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 11 May 2026.

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