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

NCT03607539 | Completed Phase 3 Results DMC

• 1 other identifier: CIBI308C302
• Study Type: interventional
• Target: 397
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Lung Neoplasms

Outcome Measures

Primary Outcomes (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

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

Secondary Outcomes (5)

• Overall Survival (OS)

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

• Objective Response Rate (ORR) by IRRC Assessment

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

• Disease Control Rate (DCR) by IRRC Assessment

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

• Time to Response (TTR) by IRRC Assessment

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

• Duration of Response (DOR) by IRRC Assessment

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

Study Arms (2)

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

Drug: Sintilimab; Drug: Pemetrexed; Drug: Platinum

Sitilimab Placebo Comparator

PLACEBO COMPARATOR

placebo 2 vials + pemetrexed/ platinum 4 cycles then Sintilimab 200mg + pemetrexed maintains

Drug: Pemetrexed; Drug: Platinum; Drug: Placebos

Interventions

Sintilimab DRUG

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

Also known as: IBI308

Sintilimab in combination with pemetrexed and platinum

Pemetrexed DRUG

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

Sintilimab in combination with pemetrexed and platinum; Sitilimab Placebo Comparator

Platinum DRUG

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

Sintilimab in combination with pemetrexed and platinum; Sitilimab Placebo Comparator

Placebos DRUG

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

Sitilimab Placebo Comparator

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Innovent Biologics (Suzhou) Co. Ltd.: lead

Study Sites (1)

Sun Yat-Sen University Cancer Center

Guangzhou, China

Location

Related Publications (4)

• 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.

  PMID: 39884222 DERIVED

• 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.

  PMID: 39084935 DERIVED

• 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.

  PMID: 35917647 DERIVED

• 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.

  PMID: 32781263 DERIVED

MeSH Terms

Conditions

Lung Neoplasms

Interventions

sintilimab; Pemetrexed; Platinum

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Results Point of Contact

• Title: Yi Bo
• Organization: Innovent Biologics (Suzhou) Co., Ltd. (seal)

jessica.yi@innoventbio.com

+8613382419112

Study Officials

• Li Zhang, Doctor

  SunYat-senUniversity

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2018
• First Posted: July 31, 2018
• Study Start: August 23, 2018
• Primary Completion: February 13, 2023
• Study Completion: February 13, 2023
• Last Updated: February 27, 2023
• Results First Posted: February 16, 2021

Record last verified: 2023-02

Locations

CN (1)