A phase IIb, open-label, single-arm study to assess the safety and efficacy of BPI-7711 capsule in patients with metastatic or recurrent non-small cell lung cancer with EGFR mutation and T790M mutation positive.

This is a phase IIb, open-label, single arm study assessing the safety and efficacy of BPI-7711 (180 mg, orally, once daily) in China with a confirmed diagnosis of EGFR sensitizing mutation positive and T790M mutation+ unresectable, locally advanced or metastatic NSCLC, who have progressed on prior EGFR-TKIs treatment. The primary objective of the study is to assess the efficacy of BPI-7711 by assessment of ORR according to RECIST 1.1 by an Independent Central Review.

Inclusion Criteria:

• Aged at least 18 years.
• Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy.
• Radiological documentation of disease progression after the most recent EGFR-TKI treatment administered. Radiological documentation of disease progression after the most recent treatment, or intolerant to current chemotherapy, or unwilling to accept the current treatment.
• At least one non-brain measurable lesion, not previously irradiated that can be accurately measured at baseline. If only one measurable lesion, the baseline CT should be performed before the biopsy or at least 14 days after the biopsy. Prior irradiated lesion can only be used as biopsy lesion after significant progression.
• Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q).
• Patients must have central confirmation of tumor T790M mutation+ status from a biopsy sample or a plasma sample taken after confirmation of disease progression on the most recent EGFR-TKI treatment. Primary T790M mutation positive patients should provide prior written evidence before ICF signature and have not received any EGFR-TKI.
• ECOG performance status 0-1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.
• Females of child-bearing potential using contraception and must have a negative pregnancy test.

Exclusion Criteria:

• Confirmed EGFR 20 exon insertion mutation after the initial diagnosis of NSCLC.
• Treatment with any 1st or 2nd EGFR-TKI (eg, erlotinib, gefitinib, icotinib, afatinib or dacomitinib) within 5x half-life of study entry.
• Treatment with any 3rd generation EGFR TKIs target on T790M mutation.
• Treatment with any cytotoxic chemotherapy, investigational agents, CYP3A4/CYP2C19 potent inhibitor/inducer, or other anticancer drugs within 14 days of study entry.
• Prior medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
• Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to study treatment.
• Major surgery within 4 weeks of study entry; radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of study entry.
• Refractory nausea and vomiting, chronic gastrointestinal diseases or bowel resection.