Clinical Trials /

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

NCT03607539

Description:

Efficacy and Safety Evaluation of IBI308 in Patients with Advanced or Recurrent Non-squamous NSCLC

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

    <li>Brief Title: Efficacy and Safety Evaluation of Sintilimab in Patients With Advanced or Recurrent Non-squamous NSCLCli><li>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)li>

Clinical Trial IDs

    <li>ORG STUDY ID: CIBI308C302li><li>NCT ID: NCT03607539li>

Conditions

    <li>Lung Neoplasmsli>

Interventions

<td>Sintilimabtd><td>IBI308td><td>Sintilimab in combination with pemetrexed and platinumtd><td>Pemetrexedtd><td/><td>Sintilimab in combination with pemetrexed and platinumtd><td>Platinumtd><td/><td>Sintilimab in combination with pemetrexed and platinumtd><td>Placebostd><td/><td>Sitilimab Placebo Comparatortd>
DrugSynonymsArms

Purpose

Efficacy and Safety Evaluation of IBI308 in Patients with Advanced or Recurrent Non-squamous NSCLC

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.
    

Trial Arms

<td>Sintilimab in combination with pemetrexed and platinumtd><td>Experimentaltd><td>Injection; dosage form: 10ml: 100mg; frequency: 200mgQ3W; 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 maintainstd><td>
    <li>Sintilimabli><li>Pemetrexedli><li>Platinumli>
td><td>Sitilimab Placebo Comparatortd><td>Placebo Comparatortd><td>placebo 200mg + pemetrexed/ platinum 4 cycles then Sintilimab 200mg + pemetrexed maintainstd><td>
    <li>Pemetrexedli><li>Platinumli><li>Placebosli>
td>
NameTypeDescriptionInterventions

Eligibility Criteria

        Inclusion criteria

          1. Sign written informed consent before any trial-related processes are implemented;

          2. Age ≥ 18 years and <75 years;

          3. Life expectancy exceeds 3 months;

          4. 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;

          5. According to the International Lung Cancer Research Association and the American
             Association for the Classification of Cancer Classification, the 8th edition of the
             TNM 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;

          6. Confirmed for patients with EGFR or ALK targeted therapy (documentary evidence of no
             tumor EGFR-sensitive mutations and no ALK gene rearrangement)

          7. The Eastern Cancer Cooperative Group (ECOG) has a performance score of 0 or 1;

          8. 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;

          9. Adequate hematologic function, defined as absolute neutrophil count ≥1.5×109 /L,
             platelet count ≥100 ×109 /L, hemoglobin ≥9g/dL (no blood transfusion or erythropoietin
             (EPO) within 7 days) Dependency);

         10. 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;

         11. Adequate renal function, defined as serum creatinine ≤ 1.5 times ULN or measured or
             calculated creatinine clearance ≥ 60 ml / min (Cockcroft-Gault formula);

         12. 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;

         13. 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.

         14. 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.

        Exclusion criteria:

          1. 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;

          2. Currently participating in interventional clinical research or treatment, or receiving
             other research drugs or using research equipment within 4 weeks before the first dose;

          3. 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, OX-40, CD137) agent

          4. 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;

          5. Pulmonary radiation therapy of >30 Gy within 6 months prior to the first dose;

          6. Completed palliative radiotherapy within 7 days prior to the first dose;

          7. Clinical active diverticulitis, abdominal abscess, gastrointestinal obstruction and
             peritoneal metastasis;

          8. Have received a physical organ or blood system transplant;

          9. There is clinically uncontrollable pleural effusion/peritoneal effusion;

         10. known to have severe allergic reactions (≥3 grade) to the active ingredients of
             edelilimumab, pemetrexed, cisplatin, carboplatin and or any excipients;

         11. 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;

         12. 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;

         13. 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);

         14. 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;

         15. 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.

         16. There is a history of (non-infectious) pneumonia requiring steroid therapy or the
             presence of interstitial lung disease 1 year before the first dose;

         17. There are active infections that require systemic treatment;

         18. Subjects who are unable or unwilling to receive folic acid or vitamin B12
             supplementation;

         19. There are known cases of mental illness or substance abuse that may have an impact on
             compliance with the test requirements;

         20. A history of human immunodeficiency virus (HIV) infection (ie, HIV 1/2 antibody
             positive) is known.

         21. 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 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(+), HBsAg(-), anti-HBs(-), and HBV viral load (-),
             prophylactic anti-HBV therapy is not required, but viral reactivation is closely
             monitored;

         22. Active HCV-infected subjects (HCV antibody positive and HCV-RNA levels above the lower
             limit of detection);

         23. 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;

         24. 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.
      
<td>Maximum Eligible Age:td><td>N/Atd><td>Minimum Eligible Age:td><td>18 Yearstd><td>Eligible Gender:td><td>Alltd><td>Healthy Volunteers:td><td>Notd>

Primary Outcome Measures

<td>Measure:td><td>PFS (Progression Free Survival)td><td>Time Frame:td><td>up to 24 months after randomizationtd><td>Safety Issue:td><td/><td>Description:td><td>Time from the first dose of study drug to the first disease progression (imaging)td>

Secondary Outcome Measures

<td>Measure:td><td>OS (overall survival)td><td>Time Frame:td><td>up to 24 months after randomizationtd><td>Safety Issue:td><td/><td>Description:td><td>Time from the first use of the study drug to the death of the subjecttd>
<td>Measure:td><td>ORR (overall response rate)td><td>Time Frame:td><td>up to 24 months after randomizationtd><td>Safety Issue:td><td/><td>Description:td><td>The proportion of patients whose tumor volume has reduced to a predetermined value and can maintain the minimum time limit is the sum of complete and partial mitigationtd>
<td>Measure:td><td>DCRtd><td>Time Frame:td><td>up to 24 months after randomizationtd><td>Safety Issue:td><td/><td>Description:td><td/>
<td>Measure:td><td>TTRtd><td>Time Frame:td><td>up to 24 months after randomizationtd><td>Safety Issue:td><td/><td>Description:td><td/>
<td>Measure:td><td>DORtd><td>Time Frame:td><td>up to 24 months after randomizationtd><td>Safety Issue:td><td/><td>Description:td><td/>
<td>Measure:td><td>378 participants with treatment-related adverse events as assessed by CTCAE v4.03td><td>Time Frame:td><td>up to 24 months after randomizationtd><td>Safety Issue:td><td/><td>Description:td><td>The investigator will evaluate all adverse events in accordance with the NCI Adverse Event General Terminology (CTCAE) Version 4.03. Any adverse events that change the CTCAE level will be recorded in the adverse event case report form/worksheet. All adverse events, regardless of CTCAE level, must be assessed for serious adverse events. All adverse events, including serious adverse events, were collected from the signed informed consent form within 90 days of the last dose, either by the investigator or by the spontaneous reported adverse events.td>

Details

<td>Phase:td><td>Phase 3td><td>Primary Purpose:td><td>Interventionaltd><td>Overall Status:td><td>Not yet recruitingtd><td>Lead Sponsor:td><td>Innovent Biologics (Suzhou) Co. Ltd.td>

Last Updated

<p/>