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Association details:
| Biomarker: | HR positive + PIK3CA H1047R + PIK3CA D350G + ER D538G |
|---|---|
| Cancer: | HER2 Negative Breast Cancer |
| Drug: | LOXO-783 (PI3Kα H1047R mutation inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
LOXO-783: A potent, highly mutant selective and brain-penetrant allosteric PI3Kα H1047R inhibitor in combination with standard of care (SOC) treatments in preclinical PI3Kα H1047R-mutant breast cancer models
Published date:
11/22/2022
Excerpt:
Combining LOXO-783 with either fulvestrant (FUL; CI at 50% inhibition = 0.28) or imlunestrant (CI at 50% inhibition = 0.43) showed increased efficacy in cell proliferation assays using the HR+, HER2-, PI3Kα H1047R- mutant T47D model. LOXO-783 also demonstrated an additive effect in combination with these endocrine therapies in vivo. Similar results were observed in a T47D model engineered to express ESR1 D538G, as well as in an HR+, HER2- PI3Kα double in-cis mutant model (H1047R/D350G) also harboring ESR1 D538G and derived from a patient who had progressed on prior letrozole plus taselisib....LOXO-783 shows additive effects when combined with SOC in breast cancers harboring the PI3Kα H1047R-mutation (as single or double in-cis mutations) in both HR+ and triple negative settings.
Secondary therapy:
fulvestrant; LY3484356
