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

Sponsor
Shanghai Kechow Pharma, Inc. (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05233332
Collaborator
(none)
186
1
4
28.7
6.5

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
186 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Anticipated Study Start Date :
Feb 28, 2022
Anticipated Primary Completion Date :
Jan 20, 2024
Anticipated Study Completion Date :
Jul 20, 2024

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. ORR(by investigator) [up to 12 months]

      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

    2. ORR(by ICR) [up to 12 months]

      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

    1. PFS(by investigator) [up to 12 months]

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

    2. PFS(by ICR) [up to 12 months]

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

    3. DOR(by investigator) [up to 12 months]

      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

    4. DOR(by ICR) [up to 12 months]

      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

    5. DCR(by investigator) [up to 12 months]

      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

    6. DCR(by ICR) [up to 12 months]

      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

    7. OS [up to 24 months]

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

    8. Number of Adverse Events [up to 12 months]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Beijing Oncology Hospital Beijing Beijing China

    Sponsors and Collaborators

    • Shanghai Kechow Pharma, Inc.

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Shanghai Kechow Pharma, Inc.
    ClinicalTrials.gov Identifier:
    NCT05233332
    Other Study ID Numbers:
    • HL-085-201
    First Posted:
    Feb 10, 2022
    Last Update Posted:
    Feb 10, 2022
    Last Verified:
    Feb 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Shanghai Kechow Pharma, Inc.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 10, 2022