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 (https://clinicaltrials.gov/ct2/show/NCT01011439). 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 has been conducted by Independent Central Review and data is available .
MAJOR HIGHLIGHTS OF THE CLINICAL DATA
As per the study protocol, data collection was limited to 6-months. Thus, clinical data were not collected from patients under compassionate use treatment. The clinical activity assessment in evaluable patients was based on the investigators' review using the modified Response Evaluation Criteria in Solid Tumors (mRECIST).
· 14 out of 28 (50%) evaluable patients completed 6-month duration of the trial.
· 9 out of 14 patients (64.2%) were approved by their respective ethical committees to continue the treatment.
· 5 of the 9 patients on compassionate use had received Milciclib for a total of 9, 9, 11, 13 and 16 months.
· As of 1 September 2019, the remaining 4 patients continuing the treatment are in their 10th, 11th, 11th and 12th months.
· Both median TTP and PFS were 5.9 months (95% Confidence Interval ("CI") 1.5-6.7 months) out of the 6-months duration of the trial.
· 17 of 28 (60.7%) evaluable patients showed 'Stable Disease' (SD; met at least once in an 8-week interval).
· One patient (3.6%) showed 'Partial Response' (PR).
· 18 of 28 (64.3%) evaluable patients showed 'Clinical Benefit Rate' defined as CBR=CR+PR+SD (with CR representing Complete Remission).
We intend to initiate Phase 2b in HCC patients with Milciclib in combination with a Tyrosine-Kinase Inhibitor (TKI), such as Sorafenib or Regorafenib in Q2 2021.
Investigator Initiated Clinical Study:Safety and Clinical Activity of Combination Treatment with Regorafenib and Milciclib in Liver Transplant Patients with Hepatocellular Carcinoma Recurrence
- Seven patients enrolled to date in this ongoing study
- Combination treatment of Milciclib and Regorafenib was well tolerated with manageable toxicities
- Mean AFP levels reduced by 20% within one month of treatment
- Patients treated for longer duration had 50% reduction in AFP levels
- Currently, patients enrolled in the study are in 2 to 10 months of treatment period