A Phase Ib Study of AZD9291 as Part of Combination Therapy in Patients with Non-Small Cell Lung Cancer which Has Continued to Grow Despite EGFR-Targeting Therapy

Full Title

A Multi-Arm, Phase Ib, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of AZD9291 in Combination With Ascending Doses of Novel Therapeutics in Patients with EGFRm+ Advanced NSCLC Who Have Progressed Following Therapy With an EGFR TKI (TATTON)

Purpose

Most non-small cell lung cancers (NSCLC) with epidermal growth factor receptor (EGFR) mutations that are treated with the standard therapy erlotinib eventually come back or continue to grow despite this treatment. In many patients, the resistance to EGFR inhibitors like erlotinib is due to a mutation called EGFR T790M.

AZD9291 (osimertinib) is effective when used alone for shrinking tumors in patients with NSCLC that has stopped responding to EGFR inhibitors, especially those with tumors containing the EGFR T790M mutation. In this study, researchers are evaluating the safety of AZD9291 when given in combination with other drugs that are active in cell pathways that may be important after other EGFR-targeting drugs have stopped working. They will also see if these drug combinations are more effective against lung cancer than AZD9291 given alone.

Patients in this study will all receive the same dose of AZD9291. They will be randomly assigned to also receive varying doses of one of the following investigational drugs:

  • MEDI4736, an antibody designed to boost the body’s immune system against cancer by targeting a protein on tumor cells called PD-L1.
  • AZD6094, which blocks a protein that promotes cancer growth called cMET.
  • Selumetinib, which blocks a cancer-promoting protein called MEK.

MEDI4736 is given intravenously (by vein), while the other three drugs are taken orally (by mouth).

Eligibility

To be eligible for this study, patients must meet several criteria, including but not limited to the following:

  • Patients must have EGFR-mutant NSCLC that has continued to grow despite an EGFR-targeting therapy such as erlotinib, gefitinib, or afatinib.
  • Patients’ tumors must demonstrate evidence of a mutation that makes the cancer resistant to EFGR inhibitors.
  • At least 14 days must pass between completion of prior therapies and entry into the study.
  • This study is for patients age 18 and older.

For more information and to inquire about eligibility for this study, please contact Dr. Helena Yu at 646-888-4274.

Protocol

14-161

Phase

I

Investigator

Co-Investigators

Locations