Timothy A. Yap, MBBS, PhD, on Advanced Solid Tumors With DNA Damage Response Defects: Early Data on Elimusertib
AACR Annual Meeting 2022
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).
Lillian L. Siu, MD, of Canada’s Princess Margaret Cancer Centre, discusses biomarker-driven precision cancer medicine, the optimal sequencing of immunotherapy (IO) with standard treatments in curative settings, IO targets beyond PD-1/PD-L1 and combinatorial strategies, and next-generation adoptive cell therapies (Abstract PL06).
John B.A.G. Haanen, MD, PhD, of the Netherlands Cancer Institute, discusses findings from a phase I study designed to test the safety and efficacy of the CARVac (CAR-T cell-amplifying RNA vaccine) strategy to overcome poor CAR T-cell stimulation and responses in patients with CLDN6-positive advanced solid tumors. Men with testicular cancer in particular showed encouraging responses. Overall, some patients showed long-term CAR T-cell persistence more than 150 days post infusion. Partial responses seemed to deepen further over time (Abstract CT002).
Matthew L. Meyerson, MD, PhD, of the Dana-Farber Cancer Institute, discusses study findings that suggest the variation in frequency of EGFR and KRAS mutations in lung cancer may be associated with genetic ancestry in patients from Latin America. The results indicate it may be possible to identify germline alleles underpinning this link. Finding a germline locus or loci may impact the development of lung cancers with these mutations and may improve lung cancer prevention and screening for populations of Latin American origin, as well as others.
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).
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).