Based on laboratory work done by Gary Schwartz when he was at Columbia, he’s now the Cancer Center Director at Case Western, there was preclinical data looking at uterine leiomyosarcoma, which has been known to have BRCA1 and BRCA2 underlying mutations. And because of that, there was a thought that a subset of these would have problems with homologous recombination...
Based on laboratory work done by Gary Schwartz when he was at Columbia, he’s now the Cancer Center Director at Case Western, there was preclinical data looking at uterine leiomyosarcoma, which has been known to have BRCA1 and BRCA2 underlying mutations. And because of that, there was a thought that a subset of these would have problems with homologous recombination. Preclinical modeling showed that PARP inhibitor combined with temozolomide looks synergistic in early models. This was the basis for an ETECN trial 10250, which was in a single arm phase 2 study looking at temozolomide of olaparib that had a 30% response rate. And patients are still on that trial to this day. And this is an old trial. So there was clearly a benefit within that trial that there is a subset of uterine leiomyosarcoma patients that benefit from this regimen. A lot of correlative work had been done and what they had discovered was the only correlation was a response turned out to be Rad 51 foci formation. Because of that, this Phase II-III trial with the Lions was launched, which was the preclinical rationale for why we actually did this phase 2 trial.
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