Clinical Trials /

Anti-CTLA-4 Antibody Followed by Anti-PD-1 Antibody in Recurrent or Metastatic NSCLC

NCT03527251

Description:

Immunotherapy has made rapid progress in melanoma, Hodgkin's lymphoma, non-small cell lung cancer, and bladder cancer, etc. Preclinical data suggested that the use of anti-PD-1 antibody in combination with CTLA-4 receptor blockers may increase antitumor activity. The CheckMate-012 study showed that nivolumab and ipilimumab combination therapy achieved an overall response rate of 43% in unselected patients with non-small cell lung cancer, compared with 23% in the nivolumab monotherapy group; and in the PD-L1 positive subgroup, nivolumab in combination with ipilimumab showed a response rate of 57%, while nivolumab alone was 28%. This showed that the combination therapy of nivolumab and ipilimumab can increase the efficacy, but the adverse events of grade 3 or above of combination therapy reach 37%. The toxic side effects limit the widespread use of nivolumab in combination with ipilimumab therapy. However, since the action of ipilimumab is limited to the initiation of the immune response (antigen presentation and immune cell activation), and its long half-time of 15.4 days, ipilimumab can used as an induction therapy, following by the PD1 monoclonal antibody. This phase I study is aimed to evaluated the safety and efficacy of CTLA-4 antibody followed by PD-1 antibody in patients with recurrent or metastatic non-small cell lung cancer.

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Anti-CTLA-4 Antibody Followed by Anti-PD-1 Antibody in Recurrent or Metastatic NSCLC
  • Official Title: A Phase I Study Evaluating the Safety and Efficacy of CTLA-4 Antibody Ipilimumab Followed by PD-1 Antibody SHR-1210 in Patients With Recurrent or Metastatic Non-small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2018-FXY-032
  • NCT ID: NCT03527251

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
IpilimumabYervoySequential group
SHR-1210Sequential group

Purpose

Immunotherapy has made rapid progress in melanoma, Hodgkin's lymphoma, non-small cell lung cancer, and bladder cancer, etc. Preclinical data suggested that the use of anti-PD-1 antibody in combination with CTLA-4 receptor blockers may increase antitumor activity. The CheckMate-012 study showed that nivolumab and ipilimumab combination therapy achieved an overall response rate of 43% in unselected patients with non-small cell lung cancer, compared with 23% in the nivolumab monotherapy group; and in the PD-L1 positive subgroup, nivolumab in combination with ipilimumab showed a response rate of 57%, while nivolumab alone was 28%. This showed that the combination therapy of nivolumab and ipilimumab can increase the efficacy, but the adverse events of grade 3 or above of combination therapy reach 37%. The toxic side effects limit the widespread use of nivolumab in combination with ipilimumab therapy. However, since the action of ipilimumab is limited to the initiation of the immune response (antigen presentation and immune cell activation), and its long half-time of 15.4 days, ipilimumab can used as an induction therapy, following by the PD1 monoclonal antibody. This phase I study is aimed to evaluated the safety and efficacy of CTLA-4 antibody followed by PD-1 antibody in patients with recurrent or metastatic non-small cell lung cancer.

Trial Arms

NameTypeDescriptionInterventions
Sequential groupExperimentalintravenous ipilimumab following by intravenous SHR-1210
  • Ipilimumab
  • SHR-1210

Eligibility Criteria

        Inclusion Criteria:

          -  Age >=18 years old, male or female;

          -  Histologically confirmed locally advanced or metastatic non-small-cell lung cancer;

          -  At least one systemic chemotherapy regimen for locally advanced or metastatic disease
             (patients received neoadjuvant chemotherapy, concurrent chemoradiotherapy, or adjuvant
             chemotherapy within 6 months can be considered as first-line system therapy);

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1;

          -  At least one measurable lesion according to criteria RECIST v1.1;

          -  Life expectancy of at least 12 weeks;

          -  Patient has adequate bone marrow as defined by the following laboratory values:

        White blood cell ≥ 3.0 × 109/L Absolute neutrophil count ≥ 1.5 × 109/L Platelets ≥ 75 ×
        109/L

          -  Patient has adequate organ function as defined by the following laboratory values:

        In absence of liver metastases, alanine aminotransferase (ALT) and aspartate
        aminotransferase (AST) should be below 2.5 × ULN. If the patient has liver metastases, ALT
        and AST should be < 5 × ULN Total serum bilirubin < ULN; or total bilirubin ≤ 3.0 × ULN
        with direct bilirubin within normal range of the central laboratory in patients with well
        documented Gilbert's Syndrome Serum creatinine ≤ 1.5 × ULN

          -  Provide written, informed consent to participate in the study and follow the study
             procedures;

          -  Women of childbearing potential must agree and commit to the use of a highly effective
             non-hormonal method of contraception, ie, intrauterine device, bilateral tubal
             ligation, vasectomized partner, or abstinence (only when it is the preferred lifestyle
             of the patient), from the time of informed consent until 28 days after the last dose
             of the investigational products. Men and their female partners of childbearing
             potential must agree and commit to use a highly effective method of contraception (ie,
             any of the above methods or hormonal contraception associated with inhibition of
             ovulation) while on treatment and for 3 months after last dose of investigational
             products

        Exclusion Criteria:

          -  Driver gene EGFR, ALK and ROS were positive;

          -  In presence of active autoimmune disease or a history of autoimmune disease (such as
             the following, but not limited to: interstitial pneumonia, uveitis, enteritis,
             hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism,
             hypothyroidism; Patients with hormone replacement therapy can be included; Patients
             with vitiligo or asthma in childhood have been completely relieved, and no
             intervention in adults can be included; The subjects who needed medical intervention
             with bronchial dilation were ineligible;

          -  Patients are using immunity inhibitors or systemic hormone therapy for
             immunosuppression purpose (such as prednisone > 10 mg/day), except for local hormone
             therapy.

          -  Patients were known to be allergic to macromolecular protein, or any components in
             ipilimumab or SHR-1210;

          -  Patients with clinical symptoms of central nervous system metastasis (e.g. brain
             edema, requirement of hormone intervention, or brain metastases progression);

          -  Another malignancy within 2 years prior to screening, with the exception of adequately
             treated in-situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or
             non-melanomatous skin cancer;

          -  Patients with congenital or acquired immunodeficiency (such as HIV infection), or
             active hepatitis (HBV DNA≥10⁴/ml);

          -  Any severe and / or uncontrolled medical conditions.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety in the treatment of ipilimumab followed by SHR1210
Time Frame:24 months
Safety Issue:
Description:Adverse events occurring up to 30 days after the last dose of ipilimumab or SHR1210 are evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.

Secondary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:Up to 4 weeks
Safety Issue:
Description:ORR as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Measure:Clinical Benefit Response (CBR)
Time Frame:Up to 4 weeks
Safety Issue:
Description:CBR as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Measure:Progression-free Survival (PFS)
Time Frame:Up to 4 weeks
Safety Issue:
Description:PFS as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Measure:Overall survival (OS)
Time Frame:Up to 4 weeks
Safety Issue:
Description:OS as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Measure:Duration of response (DOR)
Time Frame:Up to 4 weeks
Safety Issue:
Description:DOR as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Measure:Time To Progression (TTP)
Time Frame:Up to 4 weeks
Safety Issue:
Description:TTP as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sun Yat-sen University

Trial Keywords

  • clinical trial, phase I
  • CTLA-4 antibody
  • PD-1 antibody
  • non-small cell lung cancer

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