Phase 2a Clinical Trial (CDKO-125a-010) for Milciclib as a Monotherapy for the Treatment of HCC
We recently completed a Phase 2a trial (CDKO-125a-010) of Milciclib safety and tolerability as a single therapy in sorafenib-resistant patients with HCC and will report topline data in 2H 2019. (https://clinicaltrials.gov/ct2/show/NCT01011439). In March 2019, the IDMC reviewed safety data from patients as of February 26, 2019 and concluded that the administration of Milciclib to patients with advanced HCC was not associated with unexpected signs or signals of toxicity. 28 out of 31 treated patients were evaluable, 14 completed the 6-month duration study. Oral treatment with Milciclib was well-tolerated with manageable toxicities. No drug-related deaths were recorded. The most frequent drug-related adverse events such as: diarrhea, nausea, retinal hemorrhage, fatigue, asthenia, chills, ataxia, headache, rash. 64% of patients (9 patients) were approved for compassionate use treatment by their respective ethical committees. Four of the patients received Milciclib for a total (study and compassionate use) of 9, 11, 13 and 16 months. The remaining 5 patients are continuing drug treatment for 8, 9, 9, 9 and 11 months. Objective tumor assessments according to the mRECIST guideline and the conventional RECIST 1.1 criteria are being conducted by Independent Central Review and data will be available in September 2019.
Phase 2b Clinical Trial (TZLS (201)-125a-011) for Milciclib as a Combination Therapy with a Tyrosine Kinase Inhibitor (sorafenib or regorafenib) for the Treatment of HCC
In second half of 2019, we expect to initiate a randomized, multicenter study to explore tolerability and antitumor activity of Milciclib in combination with a tyrosine kinase inhibitor (TKI), either Sorafenib or regorafenib, administered as first-line systemic therapy in adult patients with recurrent, unresectable or metastatic HCC and good liver function. Both sorafenib and regorafenib are multi-kinase inhibitor which have demonstrated 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)