Puxitatug

AstraZeneca is fine-tuning plans for a Phase 3 study for its B7-H4-targeting ADC after the drug produced encouraging response and survival results in endometrial cancer patients enrolled in an early study. The 2 mg/kg dose of puxitatug samrotecan, or P-Sam for short, achieved a 34.6% objective response rate in patients with B7-H4 positive advanced or metastatic endometrial cancer in the Phase 1/2a BLUESTAR trial. The 2.4 mg/kg dose hit a 38.5% ORR, according to data presented Saturday at the Society of Gynecologic Oncology’s annual meeting on women’s cancer in Seattle. BLUESTAR tested P-Sam in a range of B7-H4-expressing tumors. The patients with endometrial cancer had progressed after prior standard-of-care treatment, with the majority having received platinum chemotherapy. Both doses of P-Sam achieved an average seven months of progression-free survival. Matt Hellmann, AstraZeneca’s head of clinical group early oncology, told Endpoints News in an interview that there have been very few advances in second-line endometrial cancer over the past several decades. For context, chemotherapy currently produces a response rate in the 20% range and a PFS of four to five months, he said. The most common side effects of P-Sam in endometrial cancer included nausea (60%), anemia (40%) and neutropenia (36.7%). Nausea was managed with antiemetic prophylaxis, while the hematological side effects were managed by delaying or reducing doses or using growth factors and transfusions. AstraZeneca now plans to advance P-Sam into a Phase 3 trial in patients with B7-H4-positive endometrial cancer following platinum chemotherapy or immunotherapy. The study will compare the ADC with the physician’s choice of chemotherapy. The drugmaker has not yet disclosed when it expects to start the trial. P-Sam comprises a proprietary linker “warhead,” which was designed by AstraZeneca in-house, along with a topoisomerase I inhibitor payload. The company also plans to explore P-Sam’s potential in treating squamous lung cancer. Puja Sapra, AstraZeneca’s head of biologics engineering and oncology targeted discovery, said in the interview that B7-H4 is a “very clean target” because it is expressed in many tumors but not in most healthy cells. The target has been key in some noteworthy deals in recent years. In 2023, GSK paid Hansoh Pharma $85 million upfront to license its B7-H4-targeting ADC, HS-20089.