Rebastinib is a potential first-in-class investigational, orally administered, potent, and highly selective inhibitor of the TIE2 kinase that was discovered using our proprietary drug discovery platform. TIE2 is the receptor for angiopoietins ANG-1 and ANG-2, an important family of vascular growth factors. TIE2 receptors are expressed on endothelial cells and angiogenic macrophages promoting the survival, maturation, and functional integrity of the vasculature and play a key role in regulating tumor angiogenesis, invasiveness, and metastasis. Rebastinib binds potently into the switch pocket of TIE2, stabilizing the inhibitory switch and displacing the activation switch to block TIE2 signaling. Rebastinib is currently being evaluated in a Phase 1b/2 clinical study in combination with paclitaxel.
Rebastinib in Combination with Paclitaxel
The Phase 1b/2 study of rebastinib in combination with paclitaxel is a two-part, open-label, multicenter study assessing the safety, tolerability, anti-tumor activity and pharmacokinetics of rebastinib in patients with advanced or metastatic solid tumors. Below are highlights from the two most advanced cohorts:
- Rebastinib in Combination with Paclitaxel in Patients with Advanced or Metastatic Platinum-resistant Ovarian Cancer: Preliminary results presented at the ESMO Virtual Congress 2020 demonstrated a 38% objective response rate, confirmed and unconfirmed, and a clinical benefit rate at eight weeks of 88% in the modified intent-to-treat population. Treatment with rebastinib 50 mg BID in combination with paclitaxel was generally well-tolerated, with treatment-emergent adverse events (TEAEs) consistent with findings from Part 1 of the study and consistent with the first-in-human study of rebastinib, or known to be associated with treatment with paclitaxel. Enrollment in Stage 2 of the platinum-resistant ovarian cancer cohort is complete and further efficacy and safety evaluation is ongoing. We expect to present additional data from this cohort in the third quarter of 2021.
- Rebastinib in Combination with Paclitaxel in Patients with Advanced Endometrial Cancer: Updated preliminary results from the endometrial cancer cohort in the Phase 1b/2 study were presented at the 2021 ASCO Annual Meeting. Of the 33 patients in the modified intent-to-treat (mITT) population, the median progression-free survival was 6.2 months. There were 11 partial responses (8 confirmed) and 12 patients with stable disease for an objective response rate of 33% (unconfirmed and confirmed) and 24% (confirmed only) with a median duration of response of 7.4 months. Treatment with rebastinib 50 mg BID in combination with paclitaxel was well-tolerated, with treatment-emergent adverse events consistent with findings from Part 1 of the study and consistent with first-in-human studies of rebastinib, or known to be associated with treatment with paclitaxel. Enrollment in Stage 2 of the endometrial cohort is complete and further efficacy and safety evaluation is ongoing.
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