Sintilimab in Combination With Gemcitabine and Platinum-Based Chemotherapy as First-Line Therapy for Advanced or Metastatic Squamous NSCLC
Condition: Squamous NSCLC
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Sintilimab; Gemcitabine; Cisplatin; Placebo; Carboplatin
Intervention description: 200mg, Q3W, day1, I.V.; consecutive cycles; 1000mg/m^2, Q3W, day 1and 8, I.V.; first 4 or 6 consecutive cycles.; 75 mg/m^2, Q3W, day1, I.V.; first 4 or 6 consecutive cycles.; NA, Q3W, day1, I.V.; consecutive cycles; AUC 5mg/ml/min, Q3W, day1, I.V.; first 4 or 6 consecutive cycles.
Intervention MeSH terms: Carboplatin; Gemcitabine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 357.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

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

Eligibility criteria:

        Inclusion Criteria:

          1. Participants must sign written ICF prior tothe implementation of any procedures
             related to the study;

          2. Aged ≥ 18 years and ≤ 75 years;

          3. With a life expectancy of more than 3 months;

          4. 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;

          5. 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;

          6. With an ECOG PS score of 0 or 1;

          7. 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;

          8. 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);

          9. 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;

         10. Adequate renal function, defined as CCr ≥ 50 mL/min (Cockcroft-Gault formula);

         11. 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;

         12. 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;

         13. 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.

        Exclusion Criteria:

          1. 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;

          2. Participants with known EGFR-sensitive mutations or ALK rearrangement;

          3. 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;

          4. 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);

          5. 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;

          6. With active hemoptysis, active diverticulitis, abdominal abscess, gastrointestinal
             obstruction, and peritoneal metastases requiring clinical intervention;

          7. Have undergone solid organ transplantation or hematologic transplantation;

          8. 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);

          9. 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.;

         10. With Class III-IV congestive cardiac failure (based on New York Heart Association
             Classification) or poorly controlled and clinically significant arrhythmia;

         11. 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);

         12. With known allergy to the active ingredients and/or any excipient of sintilimab ,
             gemcitabine, cisplatin, orcarboplatin;

         13. 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;

         14. 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;

         15. 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;

         16. Diagnosed with other malignant tumors within 5 years before the first dose, excluding
             radically cured cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma,
             and/orradically resected carcinoma in situ. For other malignant tumors or lung cancer
             diagnosedmore than 5 years before the first dose, pathological or cytological
             diagnosis should beperformed for recurrent and metastatic lesions;

         17. Symptomatic CNS metastasis. Participants with asymptomatic brain metastases or with
             stable symptoms after treatment of brain metastases are allowed to participate in this
             study as longas meeting all of the following criteria: presence of measurable lesions
             outside the CNS;absence of metastases in midbrain, pons, cerebellum, meninges, medulla
             oblongata, or spinalcord; maintain clinical stable condition for at least 2 weeks;
             discontinue hormone therapy 14 days prior to the first dose of the study treatments;

         18. With a history of non-infectious pneumonia requiring corticosteroid therapy within
             1year prior to the first dose or with non-infectious pneumonia at present;

         19. With an active infection requiring treatment or have used systemic anti-infective
             drugs within one week prior to the first dose;

         20. With known psychiatric disorder or substance abuse that could affect the compliance
             with study requirements;

         21. Known history of HIV infection (i.e. HIV 1/2 antibody positive), known syphilis
             infection (syphilis antibody positive), or active tuberculosis;

         22. With untreated active hepatitis B;

             Note: Participants with hepatitis B who meet the following criteria are also eligible
             forinclusion:

             HBV viral load must be less than 1000 copies/mL (200 IU/mL) or below LLD prior to
             thefirst dose, and participants should receive anti-HBV treatment to avoid virus
             reactivation throughout the therapeutic phase of the study; For participants with
             HBcAb (+), HBsAg (-), HBsAb (-), and HBV load (-), close monitoring is required
             instead of prophylactic anti-HBV treatment to avoid virus reactivation;

         23. Participants with active HCV infection (HCV antibody positive and HCV-RNA level above
             the LLD);

         24. Have received live vaccines within 30 days prior to the first dose; Note: Seasonal
             inactivated influenza virus vaccines for injection are allowed, while liveattenuated
             influenza vaccines forintranasal use are not acceptable;

         25. With any medical history, disease, treatment, or laboratory abnormal finding that
             would interfere with the study results or prevent the participant from participating
             in the whole study,or the investigator believes that participation in this study is
             not in the best interest of theparticipant;

         26. With local or systemic diseases not attributing to malignancy, or with cancer-related
             secondary diseases, which would result in a high medical risk and/or uncertainty in
             survivalevaluation