AstraZeneca and Daiichi Sankyo’s Enhertu has already made waves in breast cancer treatment. Now, the companies are positioning the HER2 antibody-drug conjugate (ADC) for expansion into other tumor types with data that researchers view as very compelling.
Enhertu shrank tumors in 37.1% of patients with various types of HER2-expressing solid tumors, according to an investigator assessment of a phase 2 trial called DESTINY-PanTumor02. The responses to treatment lasted a median 11.8 months. The data will be presented at the 2023 American Society of Clinical Oncology (ASCO) annual meeting.
The early data are “really compelling” and represent “a shift in how we think about cancer care,” Bradley McGregor, M.D., from the Dana-Farber Cancer Institute and an ASCO expert, said during a press briefing. At the same event, Funda Meric-Bernstam, M.D., from the MD Anderson Cancer Center and the lead investigator of the study, also called Enhertu’s anti-tumor activity “very compelling.”
The data could open Enhertu for a tumor-agnostic approval in HER2-positive tumors regardless of their location, although Daiichi Sankyo’s head of global oncology clinical development, Mark Rutstein, M.D., declined to comment on the company’s regulatory submission plan.
Speaking about the principles of a tumor-agnostic indication in an interview with Fierce Pharma, Rutstein said the response rates and the durability of response are clinically meaningful and meet the bar for a pan-tumor indication based on precedent.
But a couple uncertainties could affect a potential tumor-agnostic application for Enhertu.
For one, Enhertu only achieved a 4% tumor response rate in patients with pancreatic cancer in the trial. The trial also included biliary tract, bladder, cervical, endometrial, ovarian and other cancers, which recorded response rates at 22%, 39%, 50%, 57.5%, 45% and 12%, respectively.
Patients with breast cancer, stomach cancer, colorectal cancer and non-small cell lung cancer, where Enhertu or other HER2 agents are approved, were excluded.
For pretreated patients with pancreatic cancer, Meric-Bernstam said the 12% response rate by central review and a 68% stable disease rate by investigator analysis were “quite favorable."
In addition, compared to patients with HER2 expression at immunohistochemistry (IHC) 2+ expression, Enhertu’s benefit looks more compelling in high HER2-expressers whose tumors had IHC 3+. In those patients, the overall response rate reached 61.3%, with a median duration of 22.1 months.
Rutstein said there's a high unmet need among these patients. The DESTINY-PanTumor02 study enrolled patients who have either failed existing standard of care or have no treatment available. Rutstein said he’s “very confident” that Enhertu “would have the capability to meet a clear unmet medical need” regardless of whether tumors are IHC 2+ or 3+.
“This is an opportunity for Enhertu to really see if we can help more patients at a very basic level,” Rutstein said.
The data are strong enough in some of the tumor types for drug developers to start thinking about running studies to examine Enhertu in earlier lines of treatment, Meric-Bernstam said.
Enhertu recently opened a new category in breast cancer treatment, winning an FDA approval to treat HER2-low cases. Patients in the DESTINY-PanTumor02 trial didn’t fit in the HER2-low category.
AZ and Daiichi are generally interested in lower-expressing populations but currently have no specific plans to study Enhertu in a HER2-low pan-tumor setting, Rutstein said.
Enhertu’s HER2-low breast cancer indication cuts the patient eligibility criteria at IHC 1 and in a post-chemotherapy setting. The phase 3 DESTINY-Breast06 study is testing the ADC in a pre-chemo setting and in patients with even lower HER2 expression. A readout is expected this year.