rebastinib (DCC-2036)

In patients with MBC, the recommended phase 2 dose of rebastinib associated with pharmacodynamic evidence of TIE2 inhibition is either 50 or 100 mg PO BID in combination with paclitaxel or eribulin.

P1/2, N=117, Completed, Deciphera Pharmaceuticals LLC | Active, not recruiting --> Completed | Phase classification: P1b/2 --> P1/2

Our studies confirmed rebastinib to be a promising drug candidate for breast cancer treatment with high oral bioavailability and reasonable safety. Our data suggest that the mechanism of action of rebastinib is not limited to CDK16 inhibition but also involves other pathways. This does not diminish the importance of rebastinib as a drug candidate, but reveals the presence of several mechanisms, suggesting a wider scope of possible applications.

Moreover, our findings indicated that DCC-2036 increased the sensitivity of TNBC chemotherapy. Therefore, this study proposes a potential drug candidate and several targets for the treatment of refractory TNBC.

Furthermore, by using TIE-2 kinase-specific inhibitors such as regorafenib or rebastinib, we demonstrated that an active TIE-2 signaling was required for optimal suppressive activity of these cells after ANGPT2 exposition. Collectively, these results support that TIE-2 M-MDSC/ANGPT2 axis represents a potential immune escape mechanism in melanoma.

CDK16 plays a critical role in TNBC and is a novel promising therapeutic target for TNBC.

P1, N=28, Terminated, Montefiore Medical Center | Recruiting --> Terminated; Unfortunately, Deciphera management decided to not move forward with the rebastinib program and are terminating early.

To determine the pharmacodynamics of immune cells in ascites, syngeneic ID8 mice were pre-treated with 10 mg/kg/day rebastinib/control for a week, followed by rebastinib with or without 20 mg/kg carboplatin + 12 mg/kg paclitaxel (chemo) for two weeks. Rebastinib exerts differential effects on tumor cells and macrophages that could contribute to its mechanism of action. Rebastinib alters immune cells and increases cytotoxic T cells in ascites. Rebastinib combined with chemotherapy extends survival in PDX and syngeneic ID8 murine models of ovarian cancer.

P1, N=24, Recruiting, Montefiore Medical Center | Trial primary completion date: Jul 2021 --> Feb 2022

P1, N=24, Recruiting, Montefiore Medical Center | N=60 --> 24

All received ≥ 1 prior regimen with paclitaxel/carboplatin; the median number of prior therapies was 5 (2, 7). Funding: Deciphera Pharmaceuticals, LLC. Clinical trial identification: NCT03601897.

P1, N=60, Recruiting, Montefiore Medical Center | Trial completion date: Jul 2020 --> Dec 2021 | Trial primary completion date: Jul 2020 --> Jul 2021