2016
DOI: 10.1200/jco.2016.34.15_suppl.2504
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Phase I trial of a first-in-class ATR inhibitor VX-970 as monotherapy (mono) or in combination (combo) with carboplatin (CP) incorporating pharmacodynamics (PD) studies.

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Cited by 30 publications
(37 citation statements)
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“…We therefore treated the THP1-A3A AML cell line with the ATR kinase inhibitor VE-822 (ATRi), a potent and specific drug that is currently being evaluated in clinical trials in combination with chemotherapy for refractory solid tumors (3335). We examined the impact of ATR inhibition in our THP1-A3A cells by inducing A3A and then treating with a range of doses of ATRi.…”
Section: Resultsmentioning
confidence: 99%
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“…We therefore treated the THP1-A3A AML cell line with the ATR kinase inhibitor VE-822 (ATRi), a potent and specific drug that is currently being evaluated in clinical trials in combination with chemotherapy for refractory solid tumors (3335). We examined the impact of ATR inhibition in our THP1-A3A cells by inducing A3A and then treating with a range of doses of ATRi.…”
Section: Resultsmentioning
confidence: 99%
“…Accordingly, replication checkpoint inhibitors (RCi) are being investigated in clinical trials for their activity as chemotherapy sensitizers (35,45,46). These RCi approaches are attractive therapeutic options due to limited toxicity in healthy tissues, wide therapeutic window, and efficacy in a broad array of cancers (47).…”
Section: Discussionmentioning
confidence: 99%
“…Results of phase 1 trials of M6620 as a single agent and in combination with either cisplatin or carboplatin have been reported. As a single agent, IV doses of up to 480 mg/m 2 administered weekly were tolerated without dose‐limiting toxicities observed . In combination with carboplatin (AUC 5) administered on day 1, recommended phase 2 dose of M6620 is 90 mg/m 2 administered intravenously on days 2 and 9 .…”
Section: Discussionmentioning
confidence: 99%
“…ATM deficiency has been reported to predict for sensitivity to ATR inhibitors in preclinical testing . As well, a patient with colorectal cancer whose tumor was ATM negative by immunohistochemical testing showed a complete response to single‐agent M6620 . Among the PPTP lines tested, exome sequencing identified predicted deleterious mutations in ATM in only the glioblastoma line GBM2 (p.G494C in exon 10) and the ALL cell line MOLT‐4 (p.S2165F in exon 45).…”
Section: Discussionmentioning
confidence: 99%
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