A Safety and Efficacy Study of INC280 Alone, and in Combination With Erlotinib, Compared to Chemotherapy, in Advanced/Metastatic Non-small Cell Lung Cancer Patients With EGFR Mutation and cMET Amplification

A Phase Ib/II, Open-label, Multicenter Trial With Oral cMET Inhibitor INC280 Alone and in Combination With Erlotinib Versus Platinum With Pemetrexed in Adult Patients With EGFR Mutated, cMET-amplified, Locally Advanced/Metastatic Non-small Cell Lung Cancer (NSCLC) With Acquired Resistance to Prior EGFR Tyrosine Kinase Inhibitor (EGFR TKI)

The purpose of this study was to determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of INC280 in combination with erlotinib in the Phase Ib of this study, and to assess the anti-tumor activity and safety of INC280 alone, and in combination with erlotinib, versus platinum with pemetrexed in the Phase II of this study, in adult patients with EGFR mutated, cMET amplified, advanced/metastatic non-small cell lung cancer with acquired resistance to prior EGFR TKI.

The decision was taken to halt study enrollment with Cohort #3 in Phase Ib. Therefore, activities for the planned Phase II were not initiated.

This decision to stop further development of this combination was taken due to the challenge for enrollment in this very rare patient population along with the rapidly evolving disease landscape setting.

Inclusion Criteria:

• Locally advanced or metastatic NSCLC
• EGFR mutation (L858R and /or ex19del)
• cMET amplification by FISH (GCN ≥ 6),
• Acquired resistance to EGFR TKI (1st or 2nd generation)
• ECOG performance status (PS) ≤ 1.

Exclusion Criteria:

• Prior treatment with 3rd generation TKI

• PhaseII : Prior treatment with any of the following agents:

  • Crizotinib, or any other cMET inhibitor or HGF-targeting inhibitor.
  • Concomitant EGFR TKI and platinum based chemotherapy as first line regimen.
  • Platinum-based chemotherapy as first line treatment