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Study of Efficacy and Safety of Nivolumab in Combination With EGF816 and of Nivolumab in Combination With INC280 in Patients With Previously Treated Non-small Cell Lung Cancer

NCT02323126

Description:

To determine the efficacy and safety of Nivolumab in combination with EGF816 and of Nivolumab in combination with INC280 in previously treated NSCLC patients

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Efficacy and Safety of Nivolumab in Combination With EGF816 and of Nivolumab in Combination With INC280 in Patients With Previously Treated Non-small Cell Lung Cancer
  • Official Title: A Phase II, Multicenter, Open-label Study of EGF816 in Combination With Nivolumab in Adult Patients With EGFR Mutated Non-small Cell Lung Cancer and of INC280 in Combination With Nivolumab in Adult Patients With cMet Positive Non-small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: CEGF816X2201C
  • SECONDARY ID: 2014-003731-20
  • NCT ID: NCT02323126

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
EGF816Nivolumab and EGF816
INC280Nivolumab and INC280
NivolumabNivolumab and EGF816

Purpose

To determine the efficacy and safety of Nivolumab in combination with EGF816 and of Nivolumab in combination with INC280 in previously treated NSCLC patients

Detailed Description

      This study has two arms:

      Arm 1 (EGF816 + nivolumab) is currently closed to new enrollment.

      Arm 2 (INC280 + nivolumab) is open and enrolling as planned.
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab and EGF816ExperimentalArm 1 (EGF816 + nivolumab) is currently closed to new enrollment.
  • EGF816
  • Nivolumab
Nivolumab and INC280ExperimentalArm 2 (INC280 + nivolumab) is open and enrolling as planned.
  • INC280
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Written informed consent must be obtained prior to any screening procedures

          -  Presence of at least one measurable lesion according to RECIST v.1.1

          -  ECOG performance status ≤ 2

          -  Patients with histologically documented locally advanced, recurrent and/or metastatic
             NSCLC

          -  Tumor tissue for determination and/or confirmation of genetic pre-requisites (i.e.
             EGFR T790M positivity post progression on EGFR TKI for Group 1; cMet status for Group
             2) must be provided for analysis

        Group 1 patients:

          -  Patients with EGFR T790M NSCLC (adenocarcinoma)

          -  Documented progression of disease according to RECIST v1.1 following primary standard
             of care (e.g. erlotinib, gefitinib)

        Group 2 patients:

          -  Patients with EGFR wild-type NSCLC

          -  Documented progression of disease according to RECIST v1.1 following standard of care
             (e.g. platinum doublet).

        Exclusion Criteria:

          -  Patients who have received more than one prior line of EGFR TKI therapy1 (applies only
             to Group 1)

          -  Previous treatment with a c-MET inhibitor or HGF-targeting therapy (applies only to
             Group 2)

          -  Patients with brain metastases. However, if radiation therapy and/or surgery has been
             completed and serial evaluation by CT (with contrast enhancement) or MRI over a
             minimum of one month demonstrates the disease to be stable and if the patient remains
             must have no need for treatment with steroids

          -  Patients who require emergent use of systemic steroids, chronic use of prednisone
             (greater than 10mg or an equivalent steroid dose daily) or emergent surgery and/or
             radiotherapy.

          -  History of allergy or hypersensitivity to nivolumab components

          -  Patients with any known or suspected, current or past history of, autoimmune disease.
             Patients with type I diabetes mellitus, hypothyroidism only requiring hormone
             replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring
             systemic treatment, or conditions not expected to recur in the absence of an external
             trigger are permitted to enroll

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

          -  Known history of testing positive for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome (AIDS)

          -  Any positive test for hepatitis B virus or hepatitis C virus indicating acute or
             chronic infection

          -  Patients with interstitial lung disease that is symptomatic or may interfere with the
             detection or management of suspected drug-related pulmonary toxicity

          -  Patients with interstitial lung disease that is symptomatic or may interfere with the
             detection or management of suspected drug-related pulmonary toxicity

        Prior therapy:

          -  Patients who have been treated with prior PD-1 and PD-L1 agents

          -  Patients who previously received agents targeting c-MET and/or EGFR T790M Note:
             Previous treatment with afatinib may be allowable after discussions between Novartis
             and Investigator.

          -  Patients with the following laboratory abnormalities:

               -  Absolute Neutrophil Count (ANC) <1.5 x 109/L

               -  Hemoglobin (Hgb) <9 g/dL

               -  Platelets <100 x 109/L

               -  Total bilirubin >1.5 x upper limit of normal (ULN). For patients with Gilbert's
                  syndrome total bilirubin >2.5 x upper limit of normal (ULN)

               -  Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 x ULN

               -  Serum creatinine >1.5 x ULN and/or measured or calculated creatinine clearance
                  <75% LLN

               -  For patients being screened for Group 2, asymptomatic serum amylase > CTCAE Grade
                  2 (1.5-2.0 x ULN). Patients with Grade 1 or Grade 2 serum amylase at the
                  beginning of the study must be confirmed to have no signs or symptoms suggesting
                  pancreatitis or pancreatic injury (e.g., elevated P-amylase, abnormal imaging
                  findings of pancreas, etc.)

               -  For patients being screened for Group 2: Serum lipase > ULN

          -  Female patients who are either pregnant or nursing.

          -  Women of child bearing potential who refuse or are not able to use a highly effective
             method of contraception as defined in the study protocol.

          -  Sexually active males unless they use a condom during intercourse while taking drug
             and for 31 weeks after the last dose of study treatment.

        Other protocol-related inclusion/exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS) rate using RECIST version1.1
Time Frame:6 month
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of participants with Adverse Events (AEs)
Time Frame:Continuously during study until 100 days after post study treatment
Safety Issue:
Description:Safety of EGF816 and Nivolumab and INC280 and Nivolumab by looking at hematology and chemistry laboratory parameters, vital signs, and electrocardiograms (ECGs)
Measure:Objective response rate (ORR)
Time Frame:baseline, every 8 weeks up to cycle 12, then every 12 weeks from cycle 13 until disease progression, consent withdrawal or death up to 1 year
Safety Issue:
Description:
Measure:Disease control rate
Time Frame:baseline, every 8 weeks upto cycle 12, then every 12 weeks from cycle 13 until disease progression, consent withdrawal or death up to 1 year
Safety Issue:
Description:
Measure:Progression free survival
Time Frame:baseline, every 8 weeks upto cycle 12, then every 12 weeks from cycle 13 until disease progression, consent withdrawal or death up to 1 year
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:Start of treatment until death, average 1 year
Safety Issue:
Description:
Measure:Plasma pharmacokinetic parameters (AUClast, AUC0-t,AUCtau,Cmax, Tmax)
Time Frame:Cycle 1: Day1, Day 8, Day 15 and Cycle 2: Day 1, Cycle 4: Day 1 Cycle 6: Day 1 and Cycle 8: Day 1 Subsequent cycles (nivolumab only): every 8th cycle until discontinuation of study treatment
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Non small cell lung cancer,
  • NSCLC,
  • EGFR-mutated,
  • EGF816,
  • INC280,
  • Nivolumab,
  • EGFR-T790M NSCLC,
  • EGFR wild-type (wt),
  • cMET positive NSCLC,
  • cMET negative NSCLC

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