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ORIN1001 + paclitaxel is an investigational combination therapy being developed for the treatment of relapsed/refractory metastatic breast cancer and advanced solid tumors. **ORIN1001** is a novel, orally administered, first-in-class and selective inhibitor of IRE1α RNAse, a target in the endoplasmic reticulum stress response pathway that is implicated in promoting cancer cell survival under stress. Inhibition of IRE1α by ORIN1001 decreases cancer cell survival and, in preclinical models, shows anti-tumor and anti-fibrotic activity. **Paclitaxel**, in this context often as Abraxane (albumin-bound paclitaxel), is a well-established microtubule stabilizer that inhibits mitosis in proliferating cancer cells. The rationale for the combination is synergistic activity observed in preclinical models, with ORIN1001 potentially increasing the sensitivity of tumor cells to chemotherapy like paclitaxel. The combination is administered with oral ORIN1001 and intravenous paclitaxel (doses such as 175 mg/m2 q3w or 100 mg/m2 qw for 3 weeks) in ongoing phase 1/2 trials for metastatic breast cancer and advanced solid tumors[1][2].
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