Sintilimab in Combination With Gemcitabine and Platinum-Based Chemotherapy as First-Line Therapy for Advanced or Metastatic Squamous NSCLC

NCT03629925 | Completed Phase 3 Results DMC

• 1 other identifier: CIBI308C303
• Study Type: interventional
• Target: 357
• Locations: 1 country
• Sites: 1

Brief Summary

Efficacy and Safety Evaluation of IBI308 in Patients with Advanced or Recurrent Squamous NSCLC

Conditions

Squamous NSCLC

Outcome Measures

Primary Outcomes (1)

• PFS(Progression Free Survival)

  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. PFS according to RECIST 1.1 as assessed by BIRRC was reported for each arm.

  Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

Secondary Outcomes (5)

• OS (Overall Survival)

  Through Database Cutoff Date of 15 October 2019 (up to approximately 13 months)

• ORR(Objective Response Rate)

  Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

• TTR (Time to Response)

  Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

• DCR (Disease Control Rate)

  Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

• DOR (Duration of Response)

  Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

Study Arms (2)

Sintilimab+ gemcitabine plus platinum

EXPERIMENTAL

Sintilimab combination arm: Sintilimab in combination with gemcitabine plus cisplatin or carboplatin

Drug: Sintilimab; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin

Placebo+gemcitabine plus platinum

PLACEBO COMPARATOR

Placebo combination arm: Placebo in combination with gemcitabine plus cisplatin or carboplatin

Drug: Gemcitabine; Drug: Cisplatin; Drug: Placebo; Drug: Carboplatin

Interventions

Sintilimab DRUG

200mg, Q3W, day1, I.V.; consecutive cycles

Also known as: IBI308

Sintilimab+ gemcitabine plus platinum

Gemcitabine DRUG

1000mg/m\^2, Q3W, day 1and 8, I.V.; first 4 or 6 consecutive cycles.

Placebo+gemcitabine plus platinum; Sintilimab+ gemcitabine plus platinum

Cisplatin DRUG

75 mg/m\^2, Q3W, day1, I.V.; first 4 or 6 consecutive cycles.

Placebo+gemcitabine plus platinum; Sintilimab+ gemcitabine plus platinum

Placebo DRUG

NA, Q3W, day1, I.V.; consecutive cycles

Placebo+gemcitabine plus platinum

Carboplatin DRUG

AUC 5mg/ml/min, Q3W, day1, I.V.; first 4 or 6 consecutive cycles.

Placebo+gemcitabine plus platinum; Sintilimab+ gemcitabine plus platinum

Eligibility Criteria

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

You may qualify if:

• Participants must sign written ICF prior tothe implementation of any procedures related to the study;
• Aged ≥ 18 years and ≤ 75 years;
• With a life expectancy of more than 3 months;
• With at least one measurable lesion confirmed by the investigator according to RECIST v1.1.
• Measurable lesions locatedin the field of previous radiotherapy or locoregional therapy canbe selected as target lesions if PD is confirmed;
• Participants with histologically or cytologically confirmed locally advanced (stage IIIB/IIIC) who are ineligible for radical surgery or concurrent chemoradiotherapy, metastatic (stage IV)or recurrent squamous NSCLC based on the "8th Edition of the TNM Classification for LungCancer" issued by the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer Classification;
• With an ECOG PS score of 0 or 1;
• Have not received any prior systemic anti-tumor therapy for advanced/metastatic disease; for participants who have received prior platinum-based adjuvant chemotherapy/radiotherapy,neoadjuvant chemotherapy/radiotherapy, or radical chemoradiotherapy, they are eligible for the study if PD occurs at \> 6 months after the last treatment;
• With adequate hematologic function, defined as ANC ≥ 1.5 × 10\^9/L, platelet count ≥ 100 × 10\^9/L, and hemoglobin ≥ 90 g/L (noblood transfusion history within 7 days);
• Adequate hepatic function, defined as TBIL ≤ 1.5 × ULN and AST as well as ALT ≤ 2.5 × ULN for all participants, or AST and ALT ≤ 5 × ULN for participants with liver metastasis;
• Adequate renal function, defined as CCr ≥ 50 mL/min (Cockcroft-Gault formula);
• Adequate coagulation function, defined as INR or PT ≤ 1.5 × ULN; for the participant who is receiving anticoagulant therapy, INR or PT within the proposed scope of the anticoagulantmedication is acceptable;
• Female participants of childbearing age should be tested negative for urine or serum pregnancy within 3 days before the first dose of the study treatments. A blood pregnancy testis required if the urine pregnancy test is inconclusive;
• For male and female participants with conception potential, highly effective contraception measures (failure rate \< 1% per year) should be taken until at least 180 days afterdiscontinuation of the study treatment;
• Note: Abstinence is acceptable as a method of contraception if it is the usual lifestyle and preferred method of contraception for the participant.

You may not qualify if:

• Histological type of nonsquamousNSCLC. The dominant cell morphology must be identified for mixed cell type (participants with squamous cell carcinoma components \> 50% can beenrolled); participants with small cell carcinoma, neuroendocrine carcinoma, and sarcoma components cannot be included;
• Participants with known EGFR-sensitive mutations or ALK rearrangement;
• Currently participating in an interventional clinical study, or treated with another study drug therapy or investigational device therapy within 4 weeks before the first dose;
• Previously received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 agents or agents targeting another stimulation or synergistically inhibiting TCR (e.g., CTLA-4, OX-40,and CD137);
• Received proprietary Chinese medicines with anti-tumor indications or immunomodulators (thymosin, interferon, interleukin, etc.) within 2 weeks prior to the first dose, or received a major surgery within 3 weeks prior to the first dose;
• With active hemoptysis, active diverticulitis, abdominal abscess, gastrointestinal obstruction, and peritoneal metastases requiring clinical intervention;
• Have undergone solid organ transplantation or hematologic transplantation;
• With clinically uncontrolled pleural effusion/ascites (participants who do not need effusion drainage or have no significant increase in effusion within 3 days after stopping drainage canbe enrolled);
• With a tumor compressing the surrounding important organs (such as esophagus) with relevant symptoms, compressing the superior vena cava, or invading the mediastinal great vessels,heart, etc.;
• With Class III-IV congestive cardiac failure (based on New York Heart Association Classification) or poorly controlled and clinically significant arrhythmia;
• With any arterial thrombosis, embolism, or ischemia within 6 months prior to enrollment, such as myocardial infarction, unstable angina, cerebrovascular accident, and transient ischemicattack. With a history of deep venous thrombosis, pulmonary embolism, or any other seriousthromboembolic events within 3 months priorto enrollment (implantable port or catheter-related thrombosis, or superficial venous thrombosis is not considered as "serious"thromboembolism);
• With known allergy to the active ingredients and/or any excipient of sintilimab , gemcitabine, cisplatin, orcarboplatin;
• With active autoimmune disease requiring systemic treatment (e.g., use of disease-modifying drugs, corticosteroids, or immunosuppressive agents) within 2 years before the first dose.Replacement therapy (e.g., thyroxine, insulin, or physiologic doses of corticosteroids foradrenal or pituitary insufficiency) is not considered systemic;
• Participants requiring long-term systemic use of corticosteroids. Participants requiring intermittent use of bronchodilators, inhaled corticosteroids, or localinjection ofcorticosteroids for COPD or asthma can be included in the study;
• Full recovery (i.e., ≤ Grade 1 or reaching the baseline, excluding asthenia or alopecia) from toxicity and/or complications caused by any intervention has not achieved before thestart oftreatment;

Sponsors & Collaborators

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

Study Sites (1)

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

Related Publications (2)

• Jiang M, Sun J, Hu C, Wu L, Fan Y, Wang Z, Liu L, Wu C, Wu F, Gao G, Li F, Wang L, Li X, Cheng L, Peng B, Zhou H, Zhou C. A tumor cornification and immune-infiltration-based scheme for anti-PD-1 plus chemotherapy response in advanced squamous cell lung carcinoma. Med. 2025 Feb 14;6(2):100516. doi: 10.1016/j.medj.2024.09.005. Epub 2024 Oct 11.

  PMID: 39395411 DERIVED

• Zhou C, Wu L, Fan Y, Wang Z, Liu L, Chen G, Zhang L, Huang D, Cang S, Yang Z, Zhou J, Zhou C, Li B, Li J, Fan M, Cui J, Li Y, Zhao H, Fang J, Xue J, Hu C, Sun P, Du Y, Zhou H, Wang S, Zhang W. Sintilimab Plus Platinum and Gemcitabine as First-Line Treatment for Advanced or Metastatic Squamous NSCLC: Results From a Randomized, Double-Blind, Phase 3 Trial (ORIENT-12). J Thorac Oncol. 2021 Sep;16(9):1501-1511. doi: 10.1016/j.jtho.2021.04.011. Epub 2021 May 25.

  PMID: 34048947 DERIVED

MeSH Terms

Interventions

sintilimab; Gemcitabine; Cisplatin; Carboplatin

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: YiBo
• Organization: Innovent Biologics (Suzhou) Co., Ltd

jessica.yi@innoventbio.com

+86 13382419112

Study Officials

• Caicun Zhou

  Shanghai Pulmonary Hospital, Shanghai, China

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: August 9, 2018
• First Posted: August 14, 2018
• Study Start: September 28, 2018
• Primary Completion: March 25, 2020
• Study Completion: September 30, 2021
• Last Updated: February 28, 2023
• Results First Posted: April 1, 2021

Record last verified: 2023-02

Locations

CN (1)