Patient case: 50-year-old male with non-small cell lung cancer; genetic feature: EGFR (T790M)

Clinical trial: A Phase I/II, Multicenter, Open-label Study of EGFRmut-TKI EGF816, Administered Orally in Adult Patients With EGFRmut Solid Malignancies

Summary: To estimate the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) (Phase l part) of EGF816 and to investigate the anti-tumor activity of EGF816 (Phase II part).


Eligibility: Inclusion Criteria: (For all patients unless otherwise specified)
  -  Histologically or cytologically confirmed locally advanced (stage IIIB not amenable to definitive multi-modality therapy including surgery) or metastatic (stage IV) EGFR mutant NSCLC.
  -  Patients with controlled brain metastases
  -  ECOG performance status: Phase I part: 0, 1, or 2; Phase II part: 0 or 1
  -  Presence of at least one measurable lesion according to RECIST 1.1
  -  Patients 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
  -  Patients must have negative hepatitis C antibody (HCV-Ab) or positive HCV-Ab but undetectable level of HCV-RNA. Note: patients with detectable HCV-RNA are not eligible for the study.
  -  For Phase I: patients must have failed no more than 3 lines of any systemic antineoplastic therapy for advanced NSCLC, including EGFR-TKI
  -  For Phase II: patients must be naïve from any systemic antineoplastic therapy in the advanced setting. Patients who have failed no more than 1 cycle of systemic antineoplastic therapy in the advanced setting are allowed.
  Exclusion criteria: (Applies to all patients unless otherwise specified)
  -  Patients with a history or presence of ILD or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e. affecting activities of daily living or requiring therapeutic intervention)
  -  Presence or history of another malignancy
  -  Undergone a bone marrow or solid organ transplant
  -  Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory)
  -  Patients 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
  -  Patients with clinically significant, uncontrolled heart disease
  -  Any prior therapies ≤ 4 weeks prior to the first dose of study treatment
  -  Patients who are receiving treatment with medications that are known to be strong inhibitors or inducers of CYP3A4/5 and cannot be discontinued 1 week prior to the start of EGF816 treatment and for the duration of the study.
  -  Patients who have impairment of GI function or GI disease that may significantly alter the absorption of EGF816 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome)
  -  Patients who are receiving treatment with any enzyme-inducing anticonvulsant that cannot be discontinued at least 1 week before first dose of study treatment, and for the duration of the study
  -  Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception
  -  Sexually active males unless they use a condom during intercourse while taking drug and for 3 months after stopping treatment Other protocol-defined inclusion and exclusion criteria may apply.

Relevance to patient case: possibly relevant