Newswise — HOUSTON – The University of Texas MD Anderson Cancer Center and Spectrum Pharmaceuticals have signed a licensing agreement that covers discoveries by MD Anderson researchers about the company’s drug poziotinib, a targeted therapy for lung cancer.

A research team led by John Heymach, M.D., Ph.D., professor and chair of Thoracic/Head and Neck Medical Oncology, found that poziotinib’s size and structure make it a good fit for non-small cell lung cancer with an alteration called an exon 20 insertion in either the epidermal growth factor receptor (EGFR) or the human epidermal growth factor receptor 2 (HER2).

Patients with the exon 20 alteration have had no options for successful treatment.  The drug is in phase II clinical trials for these patients at MD Anderson and in a multi-center trial sponsored by Spectrum.

“John Heymach and his Lung Cancer Moon Shot team uncovered the potential of Spectrum’s drug poziotinib to help a neglected group of lung cancer patients and then worked closely with the company to bring this targeted therapy to clinical trial rapidly,” said Ferran Prat, Ph.D., J.D., MD Anderson senior vice president, research administration and industry relations.

“We are pleased to continue our collaboration with Spectrum under this agreement, which highlights how MD Anderson allies with private sector partners to provide new options for cancer patients.”

Researchers recently published their scientific findings in the journal Nature Medicine, and early results of MD Anderson’s phase II clinical trial were first reported at an international meeting last fall.

“We have been aggressively pursuing the potential of exon 20 mutations and treatment with poziotinib since the inception of our relationship with MD Anderson, but we’ve both only begun to scratch the surface of the science and poziotinib’s potential as a targeted treatment for various solid tumors,” said Joe Turgeon, president and CEO of Spectrum. “Late-stage poziotinib clinical data targeting the exon 20 mutation are promising, and we are thrilled to enter this new agreement that strengthens and potentially extends our patent protection until 2037 as we continue this journey of discovery together.”

About 3 percent of patients with either EGFR or HER2 non-small cell lung cancer have the exon 20 insertion, amounting to about 7,000 people diagnosed annually in the United States. Other approved EGFR inhibitors achieved response rates ranging from 3 percent to 12 percent among exon 20 patients in clinical trials. Median progression-free survival for these patients has been two months.

So far in the MD Anderson trial, 7 of 11 patients (64 percent) have responded to poziotinib, with tumor shrinkage of at least 30 percent. After 6.6 months, median progression-free survival had not been reached. More detailed data from the trial will be reported later this year.

“A deep dive into exon 20”

Heymach says his team decided “to do a deep dive into exon 20” as part of its drug repurposing pipeline project opened under MD Anderson’s Moon Shots Program™, a collaborative effort to accelerate the development of scientific discoveries into life-saving advances.

Postdoctoral fellow Jacqulyne Robichaux, Ph.D., and colleagues tested targeted therapies against lung cancer cell lines with exon 20 insertions in EGFR or HER2 and found the cells were strongly resistant to those drugs.

Structural modeling conducted with Shuxing Zhang, PHARMD, Ph.D., associate professor of Experimental Therapeutics, revealed unique aspects of the target pocket in exon 20 EGFR and HER2 lung cancer. Additional structural analysis of poziotinib, which had failed against other EGFR mutations, indicated that it would more efficiently hit those exon 20 targets.

Cell line and mouse model experiments confirmed that hypothesis. The team contacted Spectrum Pharmaceuticals and collaborated to launch the first phase II trial at MD Anderson.

Heymach, Robichaux and colleagues continue to study resistance mechanisms to poziotinib and are working with MD Anderson colleagues to look at exon 20 insertions in other types of cancer.