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

Primary Purpose

CRC

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

HL-085

Vemurafenib

About this trial

This is an interventional treatment trial for CRC focused on measuring metastatic colorectal cancer (mCRC), HL-085, Vemurafenib

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Beijing Oncology HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

phase IIa: HL-085 in Subjects With BRAF V600E-Mutated CRC

phase IIa: HL-085+Vemurafenib in Subjects With BRAF V600E-Mutated CRC

phase IIa: HL-085+Vemurafenib in Subjects With RAS or other BRAF-Mutated or MEK1/2-Mutated CRC

phase IIb: HL-085+Vemurafenib in Subjects With BRAF V600E-Mutated CRC

Arm Description

12mg BID HL-085

12mg BID HL-085+720mg BID Vemurafenib

Outcomes

Primary Outcome Measures

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

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

Secondary Outcome Measures

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

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

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

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

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

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

OS is defined as the time from the date of taking drugs to the date of death due to any cause

Number of Adverse Events

Number of Treatment-Related Adverse Events as Assessed by CTCAE v5.0 will be counted

Full Information

NCT ID

NCT05233332

First Posted

January 21, 2022

Last Updated

May 29, 2023

Sponsor

Shanghai Kechow Pharma, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT05233332

Brief Title

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

Acronym

mCRC

Official Title

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)

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

February 24, 2022 (Actual)

Primary Completion Date

January 20, 2024 (Anticipated)

Study Completion Date

July 20, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shanghai Kechow Pharma, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

CRC

Keywords

metastatic colorectal cancer (mCRC), HL-085, Vemurafenib

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

186 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

phase IIa: HL-085 in Subjects With BRAF V600E-Mutated CRC

Arm Type

Experimental

Arm Description

12mg BID HL-085

Arm Title

phase IIa: HL-085+Vemurafenib in Subjects With BRAF V600E-Mutated CRC

Arm Type

Experimental

Arm Description

12mg BID HL-085+720mg BID Vemurafenib

Arm Title

phase IIa: HL-085+Vemurafenib in Subjects With RAS or other BRAF-Mutated or MEK1/2-Mutated CRC

Arm Type

Experimental

Arm Description

12mg BID HL-085+720mg BID Vemurafenib

Arm Title

phase IIb: HL-085+Vemurafenib in Subjects With BRAF V600E-Mutated CRC

Arm Type

Experimental

Arm Description

12mg BID HL-085+720mg BID Vemurafenib

Intervention Type

Drug

Intervention Name(s)

HL-085

Intervention Description

12mg BID HL-085

Intervention Type

Drug

Intervention Name(s)

Vemurafenib

Other Intervention Name(s)

ZELBORAF

Intervention Description

720mg BID Vemurafenib

Primary Outcome Measure Information:

Title

ORR（by investigator）

Description

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

Time Frame

up to 12 months

Title

ORR（by ICR）

Description

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

Time Frame

up to 12 months

Secondary Outcome Measure Information:

Title

PFS（by investigator）

Description

Phase IIa：PFS，defined as the time from first dose to the earliest documented disease progression or death due to any cause

Time Frame

up to 12 months

Title

PFS（by ICR）

Description

Phase IIb：PFS，defined as the time from first dose to the earliest documented disease progression or death due to any cause

Time Frame

up to 12 months

Title

DOR（by investigator）

Description

Time Frame

up to 12 months

Title

DOR（by ICR）

Description

Time Frame

up to 12 months

Title

DCR（by investigator）

Description

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

Time Frame

up to 12 months

Title

DCR（by ICR）

Description

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

Time Frame

up to 12 months

Title

Description

OS is defined as the time from the date of taking drugs to the date of death due to any cause

Time Frame

up to 24 months

Title

Number of Adverse Events

Description

Number of Treatment-Related Adverse Events as Assessed by CTCAE v5.0 will be counted

Time Frame

up to 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zhimei Zhu, Master

Phone

86 215201345822

zhuzm@kechowpharma.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hongqi Tian, Ph.D

Organizational Affiliation

Shanghai Kechow Pharma, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Beijing Oncology Hospital

City

Beijing

State/Province

Beijing

Country

China

Individual Site Status

Recruiting

12. IPD Sharing Statement

Learn more about this trial

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

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