Clinical trial NCT05233332: Study of HL-085 and Vemurafinib in Metastatic Colorectal Cancer (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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: CRC
Keywords: metastatic colorectal cancer (mCRC)
HL-085
Vemurafenib
Lead sponsor: Shanghai Kechow Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-10
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: ORR（by investigator）
timeFrame: up to 12 months
measure: ORR（by ICR）
timeFrame: up to 12 months
Secondary outcomes:
measure: PFS（by investigator）
timeFrame: up to 12 months
measure: PFS（by ICR）
timeFrame: up to 12 months
measure: DOR（by investigator）
timeFrame: up to 12 months
measure: DOR（by ICR）
timeFrame: up to 12 months
measure: DCR（by investigator）
timeFrame: up to 12 months
measure: DCR（by ICR）
timeFrame: up to 12 months
measure: OS
timeFrame: up to 24 months
measure: Number of Adverse Events
timeFrame: up to 12 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Oncology Hospital
state: Beijing
Study officials:
affiliation: Shanghai Kechow Pharma, Inc.
name: Hongqi Tian, Ph.D
role: STUDY_DIRECTOR
References: