AstraZeneca Reports Promising Results for P-Sam in Endometrial Cancer Trials

On March 17, AstraZeneca announced significant findings from the first human clinical trial of its ADC drug, puxitatug samrotecan (P-Sam), targeting B7-H4 in patients with endometrial cancer. According to reports from Endpoints, the results demonstrate that P-Sam shows both efficacy and safety for this patient population as the company refines its Phase III clinical study plan.

Presented at the 2025 SGO Annual Meeting, the I/IIa BLUESTAR study revealed that the 2 mg/kg dosage of P-Sam achieved a 34.6% objective response rate (ORR) in patients with B7-H4 positive, advanced, or metastatic endometrial cancer who had previously progressed on standard treatments, primarily platinum-based chemotherapy. The 2.4 mg/kg group exhibited an even higher ORR of 38.5%. Both dosage groups reported an average progression-free survival (PFS) of 7 months.

Common side effects of P-Sam included nausea (60%), anemia (40%), and neutropenia (36.7%). Matt Hellmann, head of early oncology clinical development at AstraZeneca, noted in an interview that there has been minimal advancement in second-line treatments for endometrial cancer over the past few decades. For context, traditional chemotherapy currently has an ORR of about 20% and a PFS of 4-5 months.

AstraZeneca plans to advance P-Sam into Phase III trials specifically for B7-H4 positive endometrial cancer patients who have undergone platinum chemotherapy or immunotherapy. The upcoming study will compare the ADC against standard chemotherapy regimens, although the company has not disclosed when these Phase III trials are set to begin.

Puja Sapra, head of AstraZeneca’s Biologics and Oncology Target Discovery department, emphasized that B7-H4 is a "very clean target," as it is expressed in many tumors but not in most healthy cells.

In the rapidly evolving landscape of B7-H4 ADCs, Hansen Pharmaceuticals and GSK are leading the way with their joint development of HS-20089, which is currently in Phase III trials. In October 2023, GSK secured licensing rights for HS-20089 outside of China, resulting in an $85 million upfront payment and potential milestone payments totaling $1.485 billion.

However, the development of B7-H4 ADC drugs has not been without challenges. In February, Pfizer terminated the development of felmetatug vedotin, a candidate acquired through its $43 billion purchase of Seagen, incurring a $1 billion impairment charge.

As AstraZeneca moves forward with P-Sam, the outcomes of its ongoing and future studies could significantly impact treatment options for patients with endometrial cancer, an area that has seen little innovation in recent years.