Phase 2a Clinical Trial (CDKO-125a-010) for Milciclib as a Monotherapy for the Treatment of HCC
We initiated a Phase 2a trial (CDKO-125a-010) of Milciclib safety and tolerability as a single therapy in sorafenib-resistant patients with HCC in the first half of 2017. In May 2018, the Independent Data Monitor Committee (IDMC) completed an interim analysis of tolerability data from the first eleven treated patients and recommended expansion of the initial cohort to an additional 20 patients to complete trial enrollment in December 2018. Top-line data from this trial is expected in 2Q 2019. Sorafenib-resistant HCC patients typically, have an advanced form of the disease with poor prognosis and an average overall survival expectancy of 3-5 months.
Highlights from the trial:
- 7 of the 31 treated patients completed 6 months in the trial.
- 4 patients were approved under the compassionate use program by the respective ethical committees.
- One patient completed 8 months, another completed 13 months of treatment and the third patient completed 15 months with no apparent signs of toxicity prior to stopping treatment.
- The fourth patient is continuing compassionate use, has completed 8 months of treatment.
Phase 2b Clinical Trial (TZLS (201)-125a-011) for Milciclib as a Combination Therapy with sorafenib for the Treatment of HCC
In 2019, we expect to initiate a randomized, multicenter study to explore tolerability and antitumor activity of Milciclib in combination with Sorafenib, administered as first-line systemic therapy in adult patients with recurrent, unresectable or metastatic HCC and good liver function. Sorafenib is a multi-kinase inhibitor which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo.
Preclinical data presented at the AASLD meeting in November 2018, demonstrated significant tumor reduction in an orthotopic mouse model of HCC following five weeks of treatment with milciclib (-20% reduction, 30mg/kg/day), sorafenib (-20% reduction, 20 mg/kg/day) and the combination of milciclib and sorafenib (-38% reduction) relative to vehicle control.
Sorafenib (Nexavar®) treatment extends survival probability from 7.9 months (placebo control) to 10.7 months. There is a need for improvement which may be realized by combination of Milciclib with Sorafenib.
 (Llovet et al. N Engl J Med (2008) 359:378-390)