Clinical Trial 18120

Cancer Type: Thoracic
Interventions:EGF816; INC280 (Capmatinib)

Study Type: Treatment
Phase of Study: Phase I/II
Investigators:


    Overview

    Study Title

    A Phase Ib/II, Multicenter, Open-Label Study of EGF816 in Combination with INC280 in Adult Patients with EGFR Mutated Non-Small Cell Lung Cancer

    Summary

    The study determines the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of EGF816 in combination with INC280 and to estimate the preliminary anti-tumor activity of EGF816 in combination with INC280 in patients with advanced non-small cell lung cancer (NSCLC) with documented EGFR mutation.

    Objective

    Primary: Phase Ib part: To estimate the MTD or RP2D of EGF816 in combination with INC280. Phase II part: To estimate the preliminary anti-tumor activity of EGF816 in combination with INC280. Secondary: Phase Ib/II parts: To characterize the safety and tolerability of EGF816 in combination with INC280. Phase Ib part: To evaluate the preliminary anti-tumor activity of EGF816 in combination with INC280. Phase II part: To evaluate the preliminary anti-tumor activity of EGF816 in combination with INC280. Phase Ib/II parts: To characterize the PK of EGF816 and INC280.

    Inclusion Criteria

  • Histologically documented, locally advanced or recurrent (stage IIIB who are not eligible for combined modality treatment) or metastatic (Stage IV) non-small cell lung cancer (NSCLC)
  • Must have locally documented Epidermal Growth Factor Receptor (EGFR) mutation L858R and/or ex19del (or other rare activating mutations that confer sensitivity to first and second generation EGFR inhibitors (e.g., L861Q, G719X8I), or a characterized de novo EGFR T790M mutation
  • Presence of at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤1
  • Must be screened for HBV. Potential participants who are either HBsAg positive or HBV-DNA positive must be willing and able to take antiviral therapy 1-2 weeks prior to 1st dose of EGF816 treatment and continue on antiviral therapy for at least 4 weeks after the last dose of EGF816.
  • Must be screened for HCV. Must have negative hepatitis C antibody (HCV Ab) or are HCV Ab positive but with an undetectable level of HCV-RNA. Note: patients with detectable HCV-RNA are not eligible for the study.
  • Phase Ib only: documented progression of disease according to RECIST v1.1 while on continuous treatment with EGFR tyrosine kinase inhibitors (TKI) (erlotinib, gefitinib or afatinib).
  • Phase II Group 1 (EGFRmut, any T790M, any c-MET, 2/4L antineoplastic, EGFR TKI resistant) only: Patients demonstrated a documented clinical benefit (CR (any duration), PR (any duration), or SD for at least 6 months) on prior EGFR TKI (e.g., erlotinib, gefitinib or afatinib, and subsequently demonstrated progression according to RECIST v1.1.
  • Phase II Group 2 (EGFRmut, de novo T790M, any c-MET, 1/3L antineoplastic, EGFR TKI naïve) only: Advanced NSCLC patients who have not been previously treated with any therapy known to inhibit EGFR and harbor de novo T790M mutation.
  • Phase II Group 3 (EGFRmut, T790M negative, any c-MET, 1L antineoplastic) only: patients must harbor an EGFR activating mutation and must be naïve from any line of systemic antineoplastic therapy in the advanced setting.

  • Exclusion Criteria

  • Phase Ib: More than one previous treatment line with erlotinib, gefitinib or afatini; Previous treatment with any investigational agent known to inhibit EGFR (mutant or wild-type); Patients who have received more than three prior lines of antineoplastic therapies (including EGFR TKI) in advanced setting
  • Phase II Group 1 (EGFRmut, any T790M, any c-MET, 2/4L antineoplastic, EGFR TKI resistant): More than three prior lines of systemic antineoplastic therapies (including EGFR TKI) in the advanced setting; More than one previous treatment line with 1st or 2nd generation EGFR TKI (e.g., erlotinib, gefitinib, afatinib) in the advanced setting; Previous treatment with an investigational or marketed 3rd generation EGFR TKI (e.g. AZD9291, CO-1686, ASP8273, EGF816; Previous treatment with other investigational or marketed agent known to inhibitEGFR (e.g. EGF monoclonal antibody therapy, dual TKI inhibitor).
  • Phase II Group 2 (EGFRmut, de novo T790M, any c-MET, 1/3L antineoplastic, EGFR TKI naïve): More than two previous treatment lines of systemic antineoplastic therapies in the advanced setting; Previous treatment with an investigational or marketed agent that inhibits EGFR. EGFR inhibitors include (but not limited to) all generations of EGFR TKI (e.g. erlotinib, gefitinib, afatinib, AZD9291, CO-1686, ASP8273, EGF816) or other anti-EGFR or EGFR monoclonal antibody therapy or dual TKI inhibitors.
  • Phase II Group 3 (EGFRmut, T790M negative, any c-MET, 1L antineoplastic): De novo EGFR T790M mutation identified by central assessment; Previous treatment with any systemic antineoplastic therapy in the advanced setting (NSCLC stage IIIB or IV. Patients who received only one cycle of chemotherapy in the advanced setting are allowed); Chemotherapy administered as adjuvant or neo-adjuvant treatment more than six months prior to study enrollment is not considered a prior line of therapy for purposes of this study.
  • Previous treatment with a c-MET inhibitor or HGF-targeting therapy
  • Patients with brain metastases. However, patients with controlled brain metastases may participate in the trial. These patients must have completed any radiation therapy and/or surgery > 2 weeks prior to the first dose of study treatment and remain asymptomatic.
  • History of another malignancy. Exception: Have been disease-free for 3 years, or patients with a history of adequately treated in-situ carcinoma of the uterine cervix, basal or squamous cell carcinoma, non-melanomatous cancer of skin, history of stage IA melanoma that has been cured, are eligible
  • Have undergone a bone marrow or solid organ transplant
  • Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory)
  • Receiving concomitant immunosuppressive agents or chronic corticosteroids use at the time of study entry except for control of brain metastases, topical applications, inhaled sprays, eye drops or local injections
  • Clinically significant, uncontrolled cardiovascular disease
  • Presence or history of interstitial lung disease or interstitial pneumonitis
  • Have not recovered from all toxicities related to prior anticancer therapies to grade ≤1 (CTCAE v 4.03)
  • Have out of range laboratory values
  • Have the following laboratory values outside of the laboratory normal limits or cannot be corrected to within normal limits with supplements during screening: Potassium, Magnesium, Phosphorus, Total calcium (corrected for serum albumin)
  • Other protocol-defined inclusion/exclusion criteria may apply.