Metastatic endometrial cancer

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.

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.

FORT MYERS, Fla., Dec. 6, 2024 /PRNewswire/ -- Florida Cancer Specialists & Research Institute, LLC (FCS) hematologist and medical oncologist Mahdi Taha, DO, FACOI, FACP is lead author of a case report abstract published in Annals of Case Reports that highlights the vital role of genomic testing in diagnosing and treatment of inherited types of cancer. The abstract, "Clinical Utility of Comprehensive Genomic Profiling in a Rare Case of Metachronous Endometrial and Colorectal Primary Cancers," illustrates the complexities in diagnosing inherited cancers associated with Lynch Syndrome (LS) and the pivotal role of comprehensive genomic testing to inform diagnosis and guide treatment tailored to the unique genetic makeup of each patient. LS is associated with an increased risk of inherited colorectal, endometrial and other cancers. In the U.S., LS is estimated to affect as many as 1 in 300 people, resulting in a 70 to 80 percent increased risk of developing certain cancers. In the abstract, the authors note: "Early detection and precise treatment strategies, informed by genomic insights, are essential for improving outcomes in patients with Lynch Syndrome, especially in those with atypical presentations or limited family history." Dr. Taha said, "This milestone reflects the collaborative efforts and dedication to advancing cancer care that FCS has continuously supported. Our extensive next-generation testing capabilities and clinical research focus continue to positively impact patient outcomes." The abstract details the case of a 34-year-old female with stage IVb metastatic endometrial cancer complicated by colon cancer who is is currently being treated with targeted immunotherapy with positive results. FCS offers an extensive menu of genomic testing at its clinics statewide to detect oncogenic mutations in hundreds of different genes simultaneously, enabling clinicians to make faster diagnoses of a wide range of cancers while providing recommendations for clinical trials options and personalized therapies based on each patient's results. "This case report represents a significant step forward in our understanding of the importance of genomic testing in treating cancer, highlighting the power of collaboration and innovation in advancing patient care," said FCS Assistant Managing Physician David Wenk, MD. "We are proud to see FCS and its physicians leading this important work and contributing to the body of evidence that guides our practice and improves outcomes for patients worldwide." The study will be available in the printed Annals of Case Reports Volume 09, Issue 06 publication. About Florida Cancer Specialists & Research Institute, LLC: (FLCancer.com) Florida Cancer Specialists & Research Institute (FCS) offers patients access to more clinical trials than any private oncology practice in Florida. The majority of new cancer drugs recently approved for use in the U.S. were studied in clinical trials with FCS participation.* Recognized for our research, FCS is a recipient of the national Clinical Trials Participation Award presented by the American Society of Clinical Oncology (ASCO). FCS physicians, trained in prestigious medical schools and research institutes, are consistently ranked nationally as Top Doctors by U.S. News & World Report. Celebrating its 40th year in 2024, FCS has built a national reputation for excellence that is reflected in exceptional and compassionate patient care, driven by innovative clinical research, cutting-edge technologies and advanced treatments, including targeted therapies genomic-based treatment and immunotherapy. Our highest values are embodied by our outstanding team of highly trained and dedicated physicians, clinicians and staff. *Prior to approval SOURCE Florida Cancer Specialists & Research Institute WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED