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
Condition: Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: EGF816; INC280; Nivolumab
Intervention description: EGF816 150 mg once daily (QD) administered orally as a capsule; INC280 400 mg twice daily (BID) administered orally as a tablet; Nivolumab 3 mg/kg every 2 weeks (Q2W) administered by intravenous infusion
Intervention MeSH terms: Nivolumab; Nazartinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
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

Summary:

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

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
             asymptomatic without the 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 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.