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
Silvia C. Formenti, MD, of Weill Cornell Medicine, discusses research on the best way to integrate radiotherapy with immune modifiers, which might require changes in standard radiation oncology practices. Variables such as the type of treatment fields, the inclusion of draining nodal stations, the degree of exposure of circulating immune cells, the type of dose fractionation, and the timing of radiotherapy during immune checkpoint blockade all can affect the success of immunoradiotherapy combinations (Abstract SY43).
The ASCO Post Staff
Timothy A. Yap, MBBS, PhD, of The University of Texas MD Anderson Cancer Center, discusses results from a phase Ib expansion trial of the safety and efficacy of the oral ataxia telangiectasia and Rad3-related (ATR) inhibitor elimusertib in advanced solid tumors with DNA damage response defects. Elimusertib is a selective inhibitor of ATR, a key regulator of responses to DNA damage and replication stress, with antitumor activity in preclinical models of various solid tumors and lymphoma (Abstract CT006).
The ASCO Post Staff
Alana L. Welm, PhD, of the University of Utah Huntsman Cancer Institute, discusses her findings of a new pathway that regulates the antitumor immune response during metastatic outgrowth. Interfering with a particular isoform of RON kinase may cause metastatic tumors to be swarmed by T cells and killed, suggesting that new approaches to targeting this kinase may be achievable in the near future (Abstract SY32).
The ASCO Post Staff
Priscilla K. Brastianos, MD, of Harvard Medical School and Massachusetts General Hospital, talks about her efforts to better understand how brain metastases evolve genomically and to test such agents as abemaciclib, paxalisib, and entrectinib, which may stop their growth. Palbociclib, a CDK inhibitor, has already shown potential benefit. A national cooperative group trial is underway in multiple centers to identify novel treatments for patients with brain metastases, who typically have a poor prognosis (Abstract SY38).
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.
