vx-970 has been researched along with Carcinoma--Non-Small-Cell-Lung* in 2 studies
2 other study(ies) available for vx-970 and Carcinoma--Non-Small-Cell-Lung
| Article | Year |
|---|---|
Targeting Replication Stress and Chemotherapy Resistance with a Combination of Sacituzumab Govitecan and Berzosertib: A Phase I Clinical Trial.
Despite promising preclinical studies, toxicities have precluded combinations of chemotherapy and DNA damage response (DDR) inhibitors. We hypothesized that tumor-targeted chemotherapy delivery might enable clinical translation of such combinations.. In a phase I trial, we combined sacituzumab govitecan, antibody-drug conjugate (ADC) that delivers topoisomerase-1 inhibitor SN-38 to tumors expressing Trop-2, with ataxia telangiectasia and Rad3-related (ATR) inhibitor berzosertib. Twelve patients were enrolled across three dose levels.. Treatment was well tolerated, with improved safety over conventional chemotherapy-based combinations, allowing escalation to the highest dose. No dose-limiting toxicities or clinically relevant ≥grade 4 adverse events occurred. Tumor regressions were observed in 2 patients with neuroendocrine prostate cancer, and a patient with small cell lung cancer transformed from EGFR-mutant non-small cell lung cancer.. ADC-based delivery of cytotoxic payloads represents a new paradigm to increase efficacy of DDR inhibitors. See related commentary by Berg and Choudhury, p. 3557. Topics: Camptothecin; Carcinoma, Non-Small-Cell Lung; Humans; Immunoconjugates; Lung Neoplasms; Male | 2023 |
ATR Inhibitor M6620 (VX-970) Enhances the Effect of Radiation in Non-Small Cell Lung Cancer Brain Metastasis Patient-Derived Xenografts.
M6620, a selective ATP-competitive inhibitor of the ATM and RAD3-related (ATR) kinase, is currently under investigation with radiation in patients with non-small cell lung cancer (NSCLC) brain metastases. We evaluated the DNA damage response (DDR) pathway profile of NSCLC and assessed the radiosensitizing effects of M6620 in a preclinical NSCLC brain metastasis model. Mutation analysis and transcriptome profiling of DDR genes and pathways was performed on NSCLC patient samples. NSCLC cell lines were assessed with proliferation, clonogenic survival, apoptosis, cell cycle, and DNA damage signaling and repair assays. NSCLC brain metastasis patient-derived xenograft models were used to assess intracranial response and overall survival. Topics: Animals; Carcinoma, Non-Small-Cell Lung; Female; Heterografts; Humans; Isoxazoles; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Metastasis; Pyrazines; Treatment Outcome | 2021 |