Timothy A. Yap, MBBS, PhD, on Ovarian, Breast, Pancreatic, and Prostate Cancers With Genetic Mutations: A First-in-Human Trial of AZD5305
AACR Annual Meeting 2022
Timothy A. Yap, MBBS, PhD, of The University of Texas MD Anderson Cancer Center, discusses results from the PETRA study, a first-in-class, first-in-human trial of the next-generation PARP1-selective inhibitor AZD5305 in patients with BRCA1/2, PALB2, or RAD51C/D mutations in advanced or metastatic ovarian cancer, HER2-negative breast cancer, pancreatic, or prostate cancer. Target engagement was demonstrated across all dose levels, and antitumor activity was observed in selected tumor and molecular subtypes.
Related Videos
The ASCO Post Staff
Timothy A. Yap, MBBS, PhD, of The University of Texas MD Anderson Cancer Center, discusses how research is building on the success of first-generation PARP inhibitors in the clinic and the potential of novel potent PARP1-selective inhibitors, which may lead to improved patient outcomes. Given recent advances in drug discovery, says Dr. Yap, we now can go beyond PARP by drugging other key DNA damage response targets in the clinic, including ATR, WEE1, DNA-PK, RAD51, POLQ, and USP1.
The ASCO Post Staff
Ari M. VanderWalde, MD, MPH, MBioeth, of The West Clinic, discusses results from the S1616 trial involving patients with metastatic or unresectable melanoma who had primary resistance to PD-1 or PD-L1 inhibitors. Compared with ipilimumab alone, the combination of ipilimumab plus nivolumab benefited some patients: those with tumors that responded to therapy showed an increased amount of CD8+ cells. Because there is no standard treatment for metastatic melanoma after failure of PD-1 inhibitors in BRAF wild-type disease, this research may provide a viable option in the future (Abstract CT013).
The ASCO Post Staff
David A. Barbie, MD, of Dana-Farber Cancer Institute, discusses his laboratory’s studies, showing that malignant pleural mesothelioma, an inflamed cancer type with marginal response to immune checkpoint blockade, demonstrated high tumor cell STING expression and response to STING agonists in combination with natural killer cell therapies ex vivo. STING is the tumor cell stimulator of interferon genes (Abstract 4168).
The ASCO Post Staff
Patricia M. LoRusso, DO, of the Yale University School of Medicine, discusses how patients may benefit in the coming decade from discoveries about agents that target KRAS, and how important the approval of sotorasib turned out to be, as well as other agents in the research pipeline. Dr. LoRusso also talks about the scientific advances in tackling inhibition (Abstract SY20).
The ASCO Post Staff
Klaus Pantel, MD, of the University Medical Center Hamburg-Eppendorf, discusses liquid biopsy technologies and biomarkers, with a focus on circulating tumor cells and circulating tumor DNA; clinical applications such as early detection of cancer, improved staging, and surveillance of measurable residual disease; and how best to detect and monitor response to systemic therapies, as well as ways to identify therapeutic targets and resistance mechanisms (Abstract SY08).
