Study of HL-085 and Vemurafinib in Metastatic Colorectal Cancer (mCRC) (mCRC)

A Phase Ⅱ, Multicenter Open-label Study to Investigate the Efficacy and Safety of HL-085 Combined With Vemurafenib in Patients With Metastatic Colorectal Cancer (mCRC)

The study consists of the two parts, phase IIa and phase IIb.

Study Overview

• Status: Recruiting
• Conditions: CRC
• Intervention / Treatment: Drug: HL-085; Drug: Vemurafenib

Detailed Description

The study consists of the two parts, phase IIa and phase IIb. Phase IIa study is to assess the safety and the antitumor activity in patients with mCRC and to recommend reasonable dosage regimen of HL-085 for phase IIb study. Phase IIb is a pivotal study to evaluate HL-085 plus Vemurafenib in patients with BRAFV600E mCRC whose disease has progressed after 1 or 2 prior regimens in the metastatic setting.

• Study Type: Interventional
• Enrollment (Estimated): 186
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhimei Zhu, Master; Phone Number: 86 215201345822; Email: zhuzm@kechowpharma.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Beijing Oncology Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed written informed consent prior to enrollment；
• Adults 18 years of age or older, male or female;
• Histologically- or cytologically-confirmed CRC that is metastatic disease, and a) progression of disease or intolerance after line 1 or line 2 therapy，or inappropriate for line 1 therapy (for phase Ⅱa); b) progression of disease or intolerance after line 1 or line 2 therapy (for phase Ⅱb);
• Patient must have measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST version 1.1);
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
• Life expectancy ≥ 3 months;
• Able to take the medicine orally;
• Adequate bone marrow and organ function.

Exclusion Criteria:

• Prior treatment with any RAS inhibitors, RAF inhibitors, or MEK inhibitors;
• History or screening evidence of retinal diseases;
• Impaired cardiovascular function or clinically significant cardiovascular and cerebrovascular diseases;
• Previous or current neuromuscular diseases that is associated with CK elevation (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy, rhabdomyolysis syndrome);
• Impaired liver function, defined as Child-Pugh Class B or C;
• Toxicity has not recovered to grade 0 or 1 from prior anticancer therapy (except for alopecia, pigmentation, and grade 2 chemotherapy-related neurotoxicity);
• Use of any medications or foods that are strong inhibitors or inducers of cytochrome P450 (CYP) 3A4/5 within 7 days prior to the start of study treatment or during the study period, , drugs with a narrow therapeutic window for CYP1A2 metabolism.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: phase IIa: HL-085 in Subjects With BRAF V600E-Mutated CRC; 12mg BID HL-085	Drug: HL-085; 12mg BID HL-085
Experimental: phase IIa: HL-085+Vemurafenib in Subjects With BRAF V600E-Mutated CRC; 12mg BID HL-085+720mg BID Vemurafenib	Drug: HL-085; 12mg BID HL-085; Drug: Vemurafenib; 720mg BID Vemurafenib; Other Names: ZELBORAF
Experimental: phase IIa: HL-085+Vemurafenib in Subjects With RAS or other BRAF-Mutated or MEK1/2-Mutated CRC; 12mg BID HL-085+720mg BID Vemurafenib	Drug: HL-085; 12mg BID HL-085; Drug: Vemurafenib; 720mg BID Vemurafenib; Other Names: ZELBORAF
Experimental: phase IIb: HL-085+Vemurafenib in Subjects With BRAF V600E-Mutated CRC; 12mg BID HL-085+720mg BID Vemurafenib	Drug: HL-085; 12mg BID HL-085; Drug: Vemurafenib; 720mg BID Vemurafenib; Other Names: ZELBORAF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR（by investigator）	Phase IIa：ORR per the RECIST version 1.1，defined as the number of patients achieving an overall best response of CR or partial response (PR) divided by the total number of patients	up to 12 months
ORR（by ICR）	Phase Ⅱb：ORR per the RECIST version 1.1，defined as the number of patients achieving an overall best response of CR or partial response (PR) divided by the total number of patients	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS（by investigator）	Phase IIa：PFS，defined as the time from first dose to the earliest documented disease progression or death due to any cause	up to 12 months
PFS（by ICR）	Phase IIb：PFS，defined as the time from first dose to the earliest documented disease progression or death due to any cause	up to 12 months
DOR（by investigator）	Phase IIa：DOR，Duration of response is defined as subjects who show a confirmed clinical response (CR) or partial response (PR), the time from first documented evidence of CR or PR until the first documented sign of disease progression or death	up to 12 months
DOR（by ICR）	Phase IIb：DOR，Duration of response is defined as subjects who show a confirmed clinical response (CR) or partial response (PR), the time from first documented evidence of CR or PR until the first documented sign of disease progression or death	up to 12 months
DCR（by investigator）	Phase IIa：Proportion of subjects with response defined as CR, PR, and SD throughout the study from subjects first dose to disease progression or death	up to 12 months
DCR（by ICR）	Phase IIb：Proportion of subjects with response defined as CR, PR, and SD throughout the study from subjects first dose to disease progression or death	up to 12 months
OS	OS is defined as the time from the date of taking drugs to the date of death due to any cause	up to 24 months
Number of Adverse Events	Number of Treatment-Related Adverse Events as Assessed by CTCAE v5.0 will be counted	up to 12 months

Collaborators and Investigators

• Sponsor: Shanghai Kechow Pharma, Inc.
• Investigators: Study Director: Hongqi Tian, Ph.D, Shanghai Kechow Pharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2022
• Primary Completion (Estimated): January 20, 2024
• Study Completion (Estimated): July 20, 2024

Study Registration Dates

• First Submitted: January 21, 2022
• First Submitted That Met QC Criteria: February 6, 2022
• First Posted (Actual): February 10, 2022

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 29, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Vemurafenib; HL-085; metastatic colorectal cancer (mCRC)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Vemurafenib
• Other Study ID Numbers: HL-085-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No