Repurposed drug yields unprecedented response rates in metastatic lung cancer

A targeted therapy resurrected by the Moon Shots Program™ at MD Anderson has produced unprecedented response rates among patients with metastatic non-small cell lung cancer that carries a highly treatment-resistant mutation.

In a Phase II clinical trial, the drug poziotinib has shrunk tumors by at least 30% in eight of 11 (73%) non-small cell lung cancer patients whose cancer includes an epidermal growth factor receptor (EGFR) mutation called an exon 20 insertion. Shrinkage ranged from 30 to 50% among the eight patients reaching partial response. One patient has progressed on the clinical trial, which began in March. All patients experienced some tumor shrinkage.

“We’ve had no effective drugs for these patients, who historically have progression-free survival of about two months, and a response rate of less than 20 percent for other therapies,” said clinical trial leader John Heymach, M.D., Ph.D., chair of Thoracic Head and Neck Medical Oncology at MD Anderson and holder of the David Bruton Junior Chair in Cancer Research.

“These early results are highly encouraging, and our research shows that poziotinib’s structure makes it a great potential fit for attacking this mutation,” Heymach said.

The investigator-initiated clinical trial marks the latest progress in the identification and development of poziotinib for this group of patients conducted by MD Anderson’s Lung Cancer Moon Shot™, which is co-led by Heymach.

About 2% of non-small cell lung cancer patients (about 3,500 annually in the United States) have an EGFR exon 20 insertion. The trial has enrolled 27 patients and is expected to enroll up to 50. The Food and Drug Administration has approved other tyrosine kinase inhibitors against EGFR, but none have proved effective against the exon 20 insertion. 

Six of 11 patients have had their dose reduced because of side effects, mainly due to rash, but also diarrhea, mucositis and paronychia – inflammation of the tissue around finger nails and toenails.

Read more about the research in MD Anderson’s Newsroom.