Phase 1 Trial Begins Dosing Patients With Investigational Brain-penetrant HER2 Inhibitor

Phase 1 Trial Begins Dosing Patients With Investigational Brain-penetrant HER2 Inhibitor

Patient dosing has begun in Zion Pharma‘s Phase 1 clinical trial in the United States to evaluate the safety of its investigational HER2 inhibitor, ZN-A-1041, in people with HER2-positive breast cancer and other solid tumors.

“We are excited to have initiated our Phase 1 trial for ZN-A-1041,” Zack Cheng, PhD, chairman, CEO, and co-founder of Zion Pharma, said in a press release.

HER2 (human epidermal growth factor receptor 2) is a protein that promotes the growth of some cancers, including about 20% of breast cancers. When a cancer’s growth is driven by HER2, that cancer is said to be HER2-positive. Medications that inhibit the activity of this protein — which ZN-A-1041 is designed to do — can slow or stop the growth of HER2-positive tumors.

While approved targeted therapies can inhibit HER2 for breast cancer, ZN-A-1041 is being developed to fulfil a specific unmet medical need concerning the brain.

Tumors that grow in one part of the body can spread to another part of the body in a process called metastastis. Sometimes, tumors will metastasize to the brain, causing a major health concern. Tumors in the brain complicate treatment because a special cellular barrier — referred to as the blood-brain barrier (BBB) — very tightly controls what substances can pass from the blood into the brain. This normally helps keep the brain free of dangerous toxins, but it can also prevent medications from getting into the brain.

Zion Pharma is focused on the development of compounds that can bypass the BBB and penetrate the brain. ZN-A-1041 is the company’s lead compound.

“With dosing of the first patient in our Phase 1 study, Zion becomes a clinical stage company,” Cheng said. “A feat we are particularly proud of as we achieved this within 30 months of forming the company.”

The Phase 1 clinical trial (NCT04487236) aims to enroll about 84 people with HER2-positive cancers, and will be conducted in three phases.

The first two phases will determine the optimal dose for the investigational therapy. One of the phases will test multiple dosages of ZN-A-1041 alone in people with HER2-positive tumors other than breast cancer. The other phase will test multiple dosages of ZN-A-1041 in combination with the chemotherapy capecitabine (brand name Xeloda) in people with breast cancer, with or without brain metastases.

The final phase will evaluate a single dosage of ZN-A-1041, determined in the previous phases, combined with capecitabine in people with HER2-positive breast cancer who have brain metastases.

The main goal of the trial is to evaluate the safety and tolerability of the investigational medicine. The trial will also assess the treatment’s effect on survival, and measurements will be taken to understand how ZN-A-1041 moves through and is processed by the body.

“With our recent financing, we expect to complete the ZN-A-1041 Phase 1 study in the U.S. and China and advance several of our other programs into [investigational new drug application]-enabling studies,” said Ding Zhou, PhD, chief science officer and co-founder of Zion Pharma.

Cheng added: “This is an extremely exciting time for our team, and we look forward to advancing highly effective therapies to those patients in need.”