Power To The Brain! HER2-Targeted Drugs For Breast Cancer To Look Forward To!

DZD1516 is a reversible, selective HER2-targeting agent with full blood-brain barrier penetration. It has demonstrated good therapeutic response in a phase I study in patients with metastatic HER2-positive breast cancer, including breast cancer patients with central nervous system metastases.

Simply put, this is a good drug specifically for breast cancer patients with brain metastases. It is important to know that brain metastases are a high-risk type of metastasis that seriously threatens patients in all types of cancer, and the outlook is precarious if the disease is difficult to control.


The results of the first human Phase I clinical trial of DZD1516 were presented at the 2022 San Antonio Breast Cancer Symposium by lead study author Nicholas P. McAndrew, MD. In this trial, 19 patients (82.6%) underwent at least 1 post-treatment tumour assessment, and the treatment outcomes showed that patients had stable intracranial, extracranial and overall treatment assays.

"Preclinically, DZD1516 was designed to have a full full blood-brain barrier penetration effect," said McAndrew, assistant professor at UCLA, in the presentation. "Importantly, the dose-escalation trial portion of the Phase I study, by collecting cerebrospinal fluid samples from patients, allowed us to measure the extent to which the drug penetrated the blood-brain barrier.

"The reason why there were not many significant tumour remissions was that the patients enrolled were mostly drug-resistant patients who had been heavily treated previously," he said. "Importantly, the pharmacokinetic data from the phase I trial matched the previous preclinical model exactly, thus confirming that the drug can enter the patient's brain and cerebrospinal fluid well.

In the US and China, 23 patients with HER2-positive metastatic breast cancer who had relapsed after standard treatment received the drug.

In a HER2-positive brain metastasis xenograft model study, the combination of DZD1516 and DS-8201, an anti-HER2 antibody-drug coupling carrying a novel topoisomerase I inhibitor, ADC drug, showed synergistic anti-tumour effects. In the model, DS-8201 monotherapy as well as the combination of DZD1516 and DS-8201 successfully reduced tumour volume.

Dosing of DZD1516 was well tolerated by patients at doses of 25-250 mg twice daily and 25-250 mg/day, with dose-limiting toxicity only occurring at the 300 mg dose. Therefore, 250 mg was defined as the limit tolerated dose.

Patients were treated for a maximum duration of more than 3 months and common treatment adverse events (TEAEs) included headache, vomiting and decreased haemoglobin levels. Most TEAEs were manageable and reversible; four patients experienced grade 3 TEAEs with common symptoms of vomiting, nausea, fatigue, malaise, increased bilirubin binding and musculoskeletal pain. No grade 4/5 TEAEs were present.

"In some ways, the goal of designing this drug was to assemble a greater penetration of the patient's central nervous system." McAndrew said. "The next step is to combine this drug with other drugs so that we can look at its effectiveness in patients progressing on HER2-targeted therapy.