Clinical Trials /

A Study of SHR-1210 in Combination With Pemetrexed and Carboplatin in Subjects With Non-squamous NSCLC

NCT03134872

Description:

SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody. This is a randomized,Phase III, multicenter ,open-label study designed to evaluate the safety and efficacy of SHR-1210 with carboplatin and pemetrexed versus carboplatin-pemetrexed in subjects who are chemotherapy naive and have Stage IIIB/IV non-squamous NSCLC. The primary hypothesis is that SHR-1210 combined with carboplatin and pemetrexed prolongs Progression Free Survival (PFS) in per RECIST 1.1 by blinded independent central review (ITT population and population was indicated by high PD-L1 expression) compared to carboplatin and pemetrexed treatment .

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

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of SHR-1210 in Combination With Pemetrexed and Carboplatin in Subjects With Non-squamous NSCLC
  • Official Title: A Phase III, Randomized, Open-Label, Multi-center Study of SHR-1210(Anti-PD-1 Antibody) in Combination With Pemetrexed and Carboplatin as First Line Therapy in Subjects With Advanced/Metastatic Non-squamous Non-small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: SHR-1210-III-303-NSCLC
  • NCT ID: NCT03134872

Conditions

  • Lung Neoplasms
  • Carcinoma, Non-Small-Cell Lung
  • Respiratory Tract Neoplasms
  • Thoracic Neoplasms
  • Lung Diseases
  • Respiratory Tract Disease
  • Neoplasms by Site
  • Neoplasm, Bronchial
  • Carcinoma, Bronchogenic

Interventions

DrugSynonymsArms
SHR-1210SHR-1210+Chemotherapy
CarboplatinSHR-1210+Chemotherapy
PemetrexedSHR-1210+Chemotherapy

Purpose

SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody. This is a randomized,Phase III, multicenter ,open-label study designed to evaluate the safety and efficacy of SHR-1210 with carboplatin and pemetrexed versus carboplatin-pemetrexed in subjects who are chemotherapy naive and have Stage IIIB/IV non-squamous NSCLC. The primary hypothesis is that SHR-1210 combined with carboplatin and pemetrexed prolongs Progression Free Survival (PFS) in per RECIST 1.1 by blinded independent central review in NSCLC Subjects (ITT population and population was indicated by high PD-L1 expression) compared to carboplatin and pemetrexed treatment .

Detailed Description

      In this study, subjects will be randomly assigned to receive either carboplatin and
      pemetrexed for 4-6 cycles followed by pemetrexed maintenance until progression or
      unacceptable toxicity, OR receive SHR-1210 combined with carboplatin and pemetrexed
      chemotherapy for 4-6 cycles followed by pemetrexed maintenance with SHR-1210 until
      progression or unacceptable toxicity for a maximum of 2 years.

      Subjects assigned to the chemotherapy arm will have the opportunity to crossover to receive
      SHR-1210 monotherapy once they experience progression of disease (PD) defined by RECIST 1.1
      and meet all crossover criteria.
    

Trial Arms

NameTypeDescriptionInterventions
SHR-1210+ChemotherapyExperimentalSubjects receive SHR-1210 200mg and pemetrexed 500 mg/m^2 and carboplatin AUC 5, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional SHR-1210 200mg and pemetrexed 500 mg/m^2 every three weeks (Q3W) maintenance for the remainder of the study or until documented PD.
  • Carboplatin
  • Pemetrexed
ChemotherapyActive ComparatorSubjects receive pemetrexed 500 mg/m^2 and carboplatin Area Under the Curve (AUC) 5, administered as IV infusion on Day 1 of each 21-day cycle for 4-6 cycles followed by optional pemetrexed 500 mg/m^2 every three weeks (Q3W) maintenance for the remainder of the study or until documented PD. If PD occurs, Subjects may be able to receive SHR-1210 Q3W for the remainder of the study or until documented PD.
  • Carboplatin
  • Pemetrexed

Eligibility Criteria

        Inclusion Criteria:

          -  1. Subjects who are chemotherapy naive and have Stage IIIB-IV non-squamous NSCLC.

          -  2. Subjects should not have a previously detected sensitizing EGFR mutation or ALK
             fusion oncogene.

          -  3. Fresh cutting or ≤6 months preservation specimens must be provided.

          -  4. No prior systemic treatment. Subjects who have received prior neo-adjuvant,
             adjuvant chemotherapy, or chemoradiotherapy with curative intent for non-metastatic
             disease must have experienced a treatment free interval of at least 12 months from
             randomization since the last chemotherapy cycle.

          -  5. Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria;

          -  6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.

          -  7. Have a life expectancy of at least 3 months.

          -  8. All baseline laboratory requirements will be assessed and should be obtained within
             14 days prior to the first administration of study treatment.

          -  9. Female Subjects of childbearing potential must have a negative serum pregnancy test
             within 3 days before the first dose and must be willing to use very efficient barrier
             methods of contraception for the course of the study through 180 days after the last
             dose of study treatment.

          -  10. Male Subjects with a female partner(s) of child-bearing potential must be willing
             to use very efficient barrier methods of contraception for the course of the study
             through 180 days after the last dose of study treatment.

          -  11. Subjects has voluntarily agreed to participate by giving written informed
             consent/assent for the trial. The subject may also provide consent/assent for Future
             Biomedical Research.

        Exclusion Criteria:

          -  1. Target Disease Exceptions

               1. Subjects with predominantly squamous cell histology NSCLC, or SCLC.

               2. Subjects with epidermal growth factor receptor (EGFR)-sensitizing mutation and/or
                  anaplastic lymphoma kinase (ALK) translocation.

               3. Subjects with no measurable disease by CT or MRI per RECIST 1.1 criteria.

               4. Subjects with carcinomatous meningitis, or symptoms of spinal cord compression.

               5. Subjects with active CNS metastases are excluded.

               6. Subjects who can receive surgical resection or radical radiotherapy.

               7. Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody
                  (including any other antibody or drug specifically targeting T-cell
                  co-stimulation or checkpoint pathways).

          -  2. Medical History and Concurrent Diseases

               1. Subjects with active, known or suspected autoimmune disease. Subjects in
                  conditions not expected to recur in the absence of an external trigger, or not
                  requiring systemic treatment are permitted to enroll.

               2. Subjects with a condition requiring systemic treatment with either
                  corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive
                  medications within 14 days of first administration of study treatment. Inhaled or
                  topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone
                  equivalent, are permitted in the absence of active autoimmune disease.

               3. Prior therapy with systemic immunostimulatory agents within 1 months of the first
                  dose of trial treatment.

               4. Subjects are currently participating and receiving study therapy or had
                  participated in a study of an investigational agent and received study therapy or
                  used an investigational device within 4 weeks or 5 half-value period life of the
                  agent, before the first dose of trial treatment.

               5. Subjects who expected to require any other form of antineoplastic therapy while
                  on study (including maintenance therapy with another agent for NSCLC).

               6. Subjects received major surgery or radiation therapy of > 30 Gy not to chest
                  within 4 weeks of the first dose of study treatment, or radiation therapy of > 30
                  Gy to chest within 24 weeks of the first dose of study treatment, or radiation
                  therapy of < 30 Gy to chest within 2 weeks of the first dose of study treatment,
                  and had not recovered from the toxicity and/or complications of the most recent
                  prior chemotherapy to Grade 1 or less (except alopecia or fatigue).

               7. Subjects with a history of interstitial lung disease, or other disease may
                  interfere with the detection or treatment of suspected drug-related lung
                  toxicity.

               8. Other active malignancy requiring concurrent intervention.

               9. Subjects with previous malignancies (except non-melanoma skin cancers, and
                  thefollowing in situ cancers: bladder, endometrial, cervical/dysplasia) are
                  excluded unless a complete remission was achieved at least 5 years prior to study
                  entry.

              10. Subjects with clinically significant cardiovascular and cerebrovascular diseases.

              11. Subjects with active pulmonary tuberculosis.

              12. Subjects have severe infections within 4 weeks of the first dose of study
                  treatment.

              13. Subjects had or plan to have allogeneic bone marrow transplantation or solid
                  organ transplant.

              14. Subjects had administration of a live, attenuated vaccine within 30 days of the
                  first dose of study treatment or anticipation that such a live attenuated vaccine
                  will be required during the study.

              15. Subjects with contraindications to platinum therapy.

          -  3. Physical and Laboratory Test Findings

               1. Known history of testing positive for human immunodeficiency virus (HIV) or

               2. known acquired immunodeficiency syndrome (AIDS).

               3. Known history of active Hepatitis B or C.

               4. Subjects with severe pleural effusion, pericardial effusion, or ascites need
                  repeated drainage.

          -  4. History of severe hypersensitivity reactions to other monoclonal antibodies, or
             intravenous infusion, or carboplatin, or pemetrexed.

          -  5. Subjects have known psychiatric or substance abuse disorder (including
             alcohol\smoking), or be regular user (including "recreational use") of any illicit
             drugs that would interfere with cooperation with the requirements of the trial.

          -  6. Has a history or current evidence of any condition, therapy, or laboratory
             abnormality that might confound the results of the study, interfere with the subject's
             participation for the full duration of the study, or is not in the best interest of
             the subject to participate, in the opinion of the treating Investigator.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival in the intent-to-treat (ITT) population
Time Frame:up to 24 months
Safety Issue:
Description:PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first. Patients who have not experienced disease progression or death at the time of analysis will be censored at the time of last tumor assessment.

Secondary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:up to 24 months
Safety Issue:
Description:Determined using RECIST v1.1 criteria, defined as best overall response (CR or PR) across all assessment time points during the period from enrolment to termination of trial treatment.
Measure:Duration of Response Rate(DoR)
Time Frame:up to 24 months
Safety Issue:
Description:Determined using RECIST v1.1 criteria
Measure:Time To Progression (TTP)
Time Frame:up to 24 months
Safety Issue:
Description:Determined using RECIST v1.1 criteria
Measure:Disease Control Rate (DCR)
Time Frame:up to 24 months
Safety Issue:
Description:Determined using RECIST v1.1 criteria
Measure:Overall Survival
Time Frame:up to 24 months
Safety Issue:
Description:OS, defined as the time from randomization to death from any cause.
Measure:Change from baseline in patient reported lung cancer symptoms
Time Frame:up to 24 months
Safety Issue:
Description:Defined as time from randomization to deterioration (10 point change) on each of the EORTC QLQ-C30 and EORTC QLQ-LC13 symptom subscales (cough, dyspnea [single item and multi item subscales], chest pain, arm/shoulder pain, or fatigue) maintained for two assessments or one assessment followed by death from any cause within 3 weeks.
Measure:Number of Subjects with treatment-related adverse events (AEs)
Time Frame:up to 24 months
Safety Issue:
Description:Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Jiangsu HengRui Medicine Co., Ltd.

Trial Keywords

  • PD-1
  • PD-L1
  • SHR-1210
  • Carboplatin
  • Pemetrexed

Last Updated

March 19, 2018