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

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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

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 group	Role	What they receive
Sintilimab in combination with pemetrexed and platinum	Experimental	Injection; 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 Comparator	Placebo comparator	placebo 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.

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)

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)
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)
Disease Control Rate (DCR) by IRRC Assessment
Measured: Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)
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)
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.

23 Aug 201831 May 2022

First posted31 Jul 2018
Study start23 Aug 2018
Primary completion15 Nov 2019
Study completion31 May 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Lung NeoplasmsStudies of the same condition, open and under way.
More trials run by Innovent Biologics (Suzhou) Co. Ltd.The 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 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
Results posted: Yes, on ClinicalTrials.gov
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