Nsclc
Conditions
Brief summary
This is a phase I, open label, dose escalation study to evaluate tolerability, safety , pharmacokinetics and efficacy in patients with KRAS mutant NSCLC by using HL-085 and Docetaxel.
Interventions
DRUGHL-085
HL-085 ( Capsule) is one MEK inhibitor.
DRUGDocetaxel
Docetaxel is an antineoplastic drug by inhibiting microtubule depolymerization, and attenuating of the effects of bcl-2 and bcl-xL gene expression.
Sponsors
Shanghai Kechow Pharma, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
If no Dose-limiting toxicity (DLT) occurs in the first three subjects in Cycle 1, the dose will be escalated to the next dose level; If a DLT occurs in one of the first three subjects, three additional subjects will be enrolled for the same dose cohort, and undergo the same procedures. Dose -escalation is performed based on the scheduled dose groups until DLT occurs in two or more subjects in a dose group which consists of 3 or 6 subjects.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. KRAS mutation NSCLC. 2. One measurable lesion as defined by RECIST 1.1 criteria for solid tumors. 3. Chemotherapy, immunotherapy or radiotherapy ≥ 4 weeks prior to starting the study treatment. 4. Surgery (except for tumor biopsy) or severe trauma ≤ 14 days prior to starting the study treatment. 5. ECOG performance status of 0-1. 6. Life expectancy ≥ 3 months. 7. Ability to take the medicine orally. 8. Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
1. Hypersensitivity to study drug ingredients or their analogues. 2. Prior therapy with MEK-inhibitor. 3. Receiving any other anti-cancer therapy at the same time . 4. Active central nervous system (CNS) lesion. 5. Bleeding symptoms at Grade 3 within 4 weeks prior to starting study treatment. 6. ECG QTcB≥480msec in screening, or history of congenital long QT syndrome； 7. Uncontrolled concomitant diseases or infectious diseases. 8. Retinal diseases (Retinal Vein Occlusion (RVO) or Retinal pigment epithelial detachment (RPED) , et al.). 9. History of HIV,HCV,HBV infection. 10. Interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis will be excluded. 11. Serum HCG test is positive. 12. Other conditions that increase the risk of study and influence the result.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events (AEs) | Duration of the study, estimated to be approximately 24 months | Number of Treatment-Related Adverse Events as Assessed by CTCAE v4.03 will be counted. |
| Maximum tolerated dose (MTD) | DLTs within the first cycle of therapy (up to 35 days) | The dose level immediately below the dose level at which more than 2 patients from a cohort of 3 to 6 patients experience a dose-limiting toxicity (DLT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | Duration of the study, estimated to be approximately 24 months | ORR is the proportion of patients with a best overall response of complete response (CR) or partial response (PR), as assessed per response evaluation criteria in solid tumors (RECIST) v1.1. |
| Peak Plasma Concentration (Cmax) | Duration of the study, estimated to be approximately 24 months | Cmax is the maximum plasma concentration of HL-085 or metabolite(s). |
| Area under the plasma concentration verus time curve(AUC) | Duration of the study, estimated to be approximately 24 months | AUC of HL-085 or metabolites(s) after repeated dosing |
Countries
China
Outcome results
None listed