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

Phase 1

Terminated

• Conditions: Nsclc
• Interventions: Drug: HL-085; Drug: Docetaxel

• Registration Number: NCT03990077
• Lead Sponsor: Shanghai Kechow Pharma, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-06-12
• Study First Submitted QC: 2019-06-15
• Study First Posted: 2019-06-18
• Study Start: 2020-05-21
• Status Verified: 2020-12
• Primary Completion: 2021-07-20
• Study Completion: 2021-07-20
• Last Update Submitted: 2021-11-29
• Last Update Posted: 2021-12-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
dose escalation of HL-085 plus Docetaxel	HL-085	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.
dose escalation of HL-085 plus Docetaxel	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Cancer Hospital Chinese Academy of Medical Science; 🇨🇳 Beijing, China