Clinical Trials /

Phase II Study of the Combination of CM082 With JS001 in Patients With Advanced NSCLC.

NCT03848611

Description:

This study was a one-arm, single-center, phase II clinical study. Patients who meet the enrollment criteria will receive CM082 tablets 150mg once daily (qd) orally (taken within half an hour after daily breakfast) in combination with JS001 (3mg/kg, once every 2 weeks, q2w), every 28 days a treatment cycle until the disease progresses , the toxicity is intolerable, the investigator or subject decides to withdraw, loses to follow up, starts using other anti-tumor treatments or dies.

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

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Study of the Combination of CM082 With JS001 in Patients With Advanced NSCLC.
  • Official Title: Phase II Study of the Combination of CM082 With JS001 in Patients With Advanced NSCLC.

Clinical Trial IDs

  • ORG STUDY ID: CM082-CA-IV-401
  • NCT ID: NCT03848611

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
CM082 plus JS001Vorolanib plus Toripalimab InjectionCM082 plus JS001

Purpose

This study was a one-arm, single-center, phase II clinical study. Patients who meet the enrollment criteria will receive CM082 tablets 150mg once daily (qd) orally (taken within half an hour after daily breakfast) in combination with JS001 (3mg/kg, once every 2 weeks, q2w), every 28 days a treatment cycle until the disease progresses , the toxicity is intolerable, the investigator or subject decides to withdraw, loses to follow up, starts using other anti-tumor treatments or dies.

Detailed Description

      The study is divided into the following five stages——screening period, treatment period, end
      of treatment / withdrawal treatment,follow-up after treatment, survival follow-up.

      Screening period Subjects should be informed and signed an informed consent form prior to
      screening assessment. Screening should be performed within 28 days prior to dosing. After the
      investigator confirms compliance with the inclusion criteria and does not meet the exclusion
      criteria, the subject may be enrolled in the study drug.

      Treatment period At this stage the subject will be treated with CM082 and JS001 until disease
      progression, intolerable toxicity, the investigator or subject decides to quit,is lost to
      follow-up, begins using other anti-tumor treatments or dies.

      During the trial, subjects received a safety assessment every 4 weeks; tumor assessments were
      performed 6 weeks after the first visit and every 8 weeks after the first tumor assessment,
      Tumor progression will be evaluated simultaneously according to RECIST criteria and iRECIST
      criteria. Subjects identified as iCPD (iRECIST criteria) should discontinue treatment.

      End of treatment / withdrawal treatment EOT visit evaluation should be performed as soon as
      possible after the subject has discontinued the test drug. Anyone who discontinues treatment
      or withdraws from treatment for reasons other than progression of the disease should perform
      a safety assessment as soon as possible, while continuing to perform a tumor assessment at
      the same frequency as the treatment period until disease progression or initiation of other
      anti-tumor treatments. However, subjects who have terminated treatment due to disease
      progression need only undergo a safety assessment and no longer have a tumor assessment. If
      the subject terminates treatment due to toxicity or other reasons at the last visit and does
      not continue taking the test drug afterwards, the visit is considered to be the end of
      treatment/exit treatment visit.

      Follow-up after treatment For subjects who completed the trial or withdrew their informed
      consent, all AEs and concomitant medications must be recorded up to 30 days after the last
      dose of the trial, and all new AEs were issued within 30 days of the last trial dose. For
      subjects who started using other anti-tumor therapies, AEs that were not severe and that the
      investigator considered unrelated to the test drug were no longer recorded.

      Survival follow-up Subjects with disease progression or other anti-tumor treatments will no
      longer undergo safety and tumor assessment, but continue to collect data on overall survival
      and follow-up treatment at telephone follow-up every 12 weeks until the patient dies or loses
      visit.

      Note: Patients who discontinue treatment due to disease progression (except for patients
      withdrawing informed consent, loss of follow-up, death) should continue to follow the tumor
      assessments according to the original frequency (no safety assessment) ). Once disease
      progression has occurred or other anti-tumor drugs have been used, a telephone survival
      follow-up is performed every 12 weeks thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
CM082 plus JS001ExperimentalPatients who meet the enrollment criteria will receive CM082 tablets 150mg once daily (qd) orally (taken within half an hour after daily breakfast) in combination with JS001 (3mg/kg, once every 2 weeks, q2w), every 28 days A treatment cycle until the disease progresses, the toxicity is intolerable, the investigator or subject decides to withdraw, loses to follow up, starts using other anti-tumor treatments or dies.
  • CM082 plus JS001

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed diagnosis of recurrence after surgery,
             inoperable resection or metastasis advanced NSCLC (III/IV period),with no specific
             driver gene mutations (EGFR or ALK).

          -  Has not received any systemic anti-tumor medication or adjust the chemotherapy regimen
             because of intolerance( but the treatment should be completed for at least 4 weeks
             prior to the first dose of study drug, and all related toxicity events have returned
             to normal or no more than Grade I of CTCAE 4.03, except for hair loss).

          -  Eastern Cooperative Group (ECOG) Performance Status score of 0 or 1.

          -  Life expectancy of at least 12 weeks.

          -  All patients are suggested tumor tissue specimens (preferably fresh tissue specimens)
             for PD-L1 expression analysis prior to enrollment.If the subject did not undergo a
             pathological examination before participating in the trial, the collected tumor tissue
             specimens will also be used for pathological examination to confirm the diagnosis of
             NSCLC.

          -  There is at least one measurable lesion according to the RECIST 1.1 standard and the
             lesion has not received radiotherapy.

          -  Patients may have a history of brain/mesis metastases, but must undergo topical
             treatment(surgery/radiotherapy) and be clinically stable for at least 3 months prior
             to the start of the study .If orticosteroids have been used before, they should be
             discontinued for at least 2 weeks before the first dose of study drug.

          -  The level of organ function must meet the following requirements (7 days before the
             first dose of study drug):

               -  Bone marrow: Absolute neutrophil count (ANC) ≥ 1.5 × 109 / L, platelet (PLT) ≥
                  100 × 109 / L, hemoglobin (HB) ≥ 9g / dL (no blood transfusion or receiving blood
                  components within 14 days before detection);

               -  Liver: serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal(ULN),
                  aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5*ULN (if
                  liver metastasis, AST, ALT allowed) ≤ 5 *ULN);

               -  Serum creatinine ≤ 1.5*ULN and endogenous creatinine clearance ≥ 50mL / min
                  (Cockcroft-Gault formula);

               -  Well-controlled hypertensive patients can be enrolled;

               -  International normalized ratio (INR), activated partial thromboplastin time
                  (aPTT) ≤ 1.5 *ULN for patients who have not received anticoagulant therapy;
                  patients who receive anticoagulant therapy should be treated within the
                  requirements of label

               -  Urine protein ≤ 1+, if urine protein > 1+, 24 hours urine protein measurement is
                  required, the total amount of which needs ≤ 1 gram;

               -  FT3, FT4, TSH normal or abnormal has no clinical significance;

               -  The heart function is normal, that is, the electrocardiogram is normal or
                  abnormal has no clinical significance. The echocardiography shows that the left
                  ventricular ejection fraction (LVEF) is greater than 50%.

          -  Serum pregnancy test results must be negative within 7 days prior to the first dose of
             the test drug for women of childbearing age; males with fertility or women who are at
             risk of pregnancy must use highly effective methods of contraception throughout the
             trial (eg oral contraceptives, pIntrauterine device, controlled libido or barrier
             contraceptive method combined with spermicide), and continued contraception for 12
             months after the end of treatment.

          -  Ability to understand the nature of this trial and give written informed
             consent.Willingness and ability to comply with trial and follow-up procedures.

        Exclusion Criteria:

          -  Patients who have previously received anti-PD-1, anti-PD-L1, anti-PD-L2 therapy, or
             VEGFR TKI therapy.

          -  Patients currently receiving anti-tumor treatment.

          -  Patients who received large surgery within 4 weeks before the first dose of the test
             drug or has not recovered from the side effects of this operation, received live
             vaccination or immunotherapy within 4 weeks before the first dose of the test drug,
             and radiotherapy was performed within 2 weeks.

          -  Subjects with a history of malignancy (unless NSCLC) were excluded unless complete
             remission was achieved at least 2 years prior to enrollment and no further treatment
             was required during the study period (the following conditions are not limited:
             non-melanoma skin cancer) , bladder carcinoma in situ, gastric carcinoma in situ,
             colonic carcinoma in situ, endometrial carcinoma in situ, cervical carcinoma in
             situ/dysplasia, melanoma carcinoma in situ or breast carcinoma in situ)

          -  Hematopoietic stimulating factors were received within 1 week prior to the first dose
             of the study drug, such as granulocyte colony-stimulating factor (G-CSF) and
             erythropoietin.

          -  HIV antibody or Treponema pallidum antibody test results are positive.

          -  If HBsAg or HBcAb is positive, HBV DNA should be tested.Patients should be excluded if
             the measurement is above the upper limit of the normal range.If HCV antibody is
             positive, HCV DNA should be tested.Patients should be excluded if the measurement is
             above the upper limit of the normal range.

          -  Those known to be allergic to recombinant humanized PD-1 monoclonal antibody drugs and
             their components; those known to be allergic to CM082 and any of its excipients.

          -  A large amount of pleural or ascites with clinical symptoms and requiring symptomatic
             treatment.

          -  Active lung disease (eg, interstitial pneumonia, pneumonia, obstructive pulmonary
             disease, asthma) or a history of active tuberculosis.

          -  Have any clinical problems out of control, including but not limited to:

               -  Persistent or active (severe) infection;

               -  Hypertension that is not effectively controlled (blood pressure lasts greater
                  than 150/90mmHg);

               -  Diabetes that is not effectively controlled;

               -  Heart disease, defined as grade III/IV congestive heart failure or heart block
                  defined by the New York Heart Association

               -  Having a history of or suspected of having an autoimmune disease;Having a history
                  of any kind of disease requiring treatment with a steroid or immunosuppressive,
                  such as: pituitary inflammation, colitis, hepatitis, nephritis, hyperthyroidism,
                  Hypothyroidism, etc.;

               -  The following situation occurred within 6 months before the first dose:

                    -  Deep vein thrombosis or pulmonary embolism;

                    -  myocardial infarction;

                    -  severe or unstable arrhythmia or angina;

                    -  percutaneous coronary intervention, acute coronary syndrome, coronary artery
                       bypass grafting;

                    -  Cerebrovascular accident, transient ischemic attack, and cerebral embolism.

          -  Have received a stem cell transplant or an organ transplant.

          -  Patients who need to use during the study or have used or the following drugs within
             14 days prior to the first dose: CYP3A4 strong inhibitor or strong inducer; warfarin
             or any other coumarin derivative anticoagulant.

          -  The investigator judges other severe, acute or chronic medical illness or laboratory
             abnormalities that may increase the risk associated with the study or may interfere
             with the interpretation of the findings.

          -  The investigator judged that the patient's compliance was poor or that there were
             other conditions that were not suitable for the trial.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate according to RECIST 1.1
Time Frame:12 months
Safety Issue:
Description:The proportion of patients with complete remission (CR) and partial remission (PR) in all patients.Disease progression will be evaluated according to RECIST 1.1.

Secondary Outcome Measures

Measure:Disease Control Rate according to RECIST 1.1 and iRECIST
Time Frame:12 months
Safety Issue:
Description:The proportion of patients with complete remission (CR),partial remission (PR) and stable diseasein(SD) all patients.Disease progression will be evaluated according to RECIST 1.1 and iRECIST.
Measure:Duration of Response according to RECIST 1.1 and iRECIST
Time Frame:12 months
Safety Issue:
Description:The time interval between the first time of being evaluated as complete response (CR) or partial response (PR) and the first time of being evaluated as progressed disease(PD).Disease progression will be evaluated according to RECIST 1.1 and iRECIST.
Measure:Time to Response to RECIST 1.1 and iRECIST
Time Frame:12 months
Safety Issue:
Description:ime from randomization to complete response (CR) or partial response (PR).Disease progression will be evaluated according to RECIST 1.1 and iRECIST
Measure:Progression-free survival
Time Frame:12 months
Safety Issue:
Description:The internal between the date of randomization and the date of disease progression, unaccepted toxicity, or death.
Measure:Overall survival
Time Frame:36 months
Safety Issue:
Description:The internal between the date of randomization and the date of death.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AnewPharma

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