Study of HL-085 Plus Docetaxel in Patients With KRAS Mutant NSCLC

Sponsor

Shanghai Kechow Pharma, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT03990077

Collaborator

(none)

Enrollment

Location

Arm

Actual Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Nsclc	Drug: HL-085 Drug: Docetaxel	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

2 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I , Single Arm, Dose Escalation Study to Evaluate Tolerability, Safety, Pharmacokinetics and Preliminary Efficacy of HL-085 Plus Docetaxel in Patients With KRAS Mutant NSCLC

Actual Study Start Date :

May 21, 2020

Actual Primary Completion Date :

Jul 20, 2021

Actual Study Completion Date :

Jul 20, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: dose escalation of HL-085 plus Docetaxel HL-085 will be administered as BID with specified dose. And Docetaxel will be taken as the instruction in the label ( 75mg/m2，IV). f 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.	Drug: HL-085 HL-085 ( Capsule) is one MEK inhibitor. Drug: Docetaxel Docetaxel is an antineoplastic drug by inhibiting microtubule depolymerization, and attenuating of the effects of bcl-2 and bcl-xL gene expression.

Arm

Intervention/Treatment

Experimental: dose escalation of HL-085 plus Docetaxel

HL-085 will be administered as BID with specified dose. And Docetaxel will be taken as the instruction in the label ( 75mg/m2，IV). f 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.

Drug: HL-085

HL-085 ( Capsule) is one MEK inhibitor.

Drug: Docetaxel

Docetaxel is an antineoplastic drug by inhibiting microtubule depolymerization, and attenuating of the effects of bcl-2 and bcl-xL gene expression.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

KRAS mutation NSCLC.
One measurable lesion as defined by RECIST 1.1 criteria for solid tumors.
Chemotherapy, immunotherapy or radiotherapy ≥ 4 weeks prior to starting the study treatment.
Surgery (except for tumor biopsy) or severe trauma ≤ 14 days prior to starting the study treatment.
ECOG performance status of 0-1.
Life expectancy ≥ 3 months.
Ability to take the medicine orally.
Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Hypersensitivity to study drug ingredients or their analogues.
Prior therapy with MEK-inhibitor.
Receiving any other anti-cancer therapy at the same time .
Active central nervous system (CNS) lesion.
Bleeding symptoms at Grade 3 within 4 weeks prior to starting study treatment.
ECG QTcB≥480msec in screening, or history of congenital long QT syndrome；
Uncontrolled concomitant diseases or infectious diseases.
Retinal diseases (Retinal Vein Occlusion (RVO) or Retinal pigment epithelial detachment (RPED) , et al.).
History of HIV,HCV,HBV infection.
Interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis will be excluded.
Serum HCG test is positive.
Other conditions that increase the risk of study and influence the result.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cancer Hospital Chinese Academy of Medical Science	Beijing		China	100021

Sponsors and Collaborators

Shanghai Kechow Pharma, Inc.

Investigators

Study Director: Hongqi Tian, PhD, Shanghai Kechow Pharma.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Shanghai Kechow Pharma, Inc.

ClinicalTrials.gov Identifier:

NCT03990077

Other Study ID Numbers:

HL-085-103

First Posted:

Jun 18, 2019

Last Update Posted:

Dec 10, 2021

Last Verified:

Dec 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung

Docetaxel

Study Results

No Results Posted as of Dec 10, 2021