Efficacy and Safety of HL-085 Combined With Vemurafenib in BRAF V600E Patients With Non-small Cell Lung Cancer: a Phase II Clinical Study

NCT05900219 | Unknown Phase 2

• 1 other identifier: HL-085-203
• Study Type: interventional
• Target: 75
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single-arm, open, multicenter phase II clinical study to evaluate the efficacy and safety of HL-085 capsules combined with Vemurafenib in the treatment of BRAF V600E mutated patients with unresectable locally advanced or metastatic NSCLC. Meanwhile, to explore the relationship between pop-PK characteristics, efficacy and safety in the treatment of HL-085 combined with Vemurafenib

Conditions

Non-small-cell Lung Cancer

Keywords

BRAF V600E mutation; NSCLC

Outcome Measures

Primary Outcomes (1)

• ORR

  Defined as the proportion of subjects with an optimal response of CR or PR over the course of the study from enrollment to disease progression (PD), dominated by IRC assessment. CR and PR must be reassessed for confirmation ≥4 weeks after first meeting mitigation criteria;

  through study completion, an average of 1 year

Secondary Outcomes (1)

• DOR

  through study completion, an average of 1 year

Study Arms (1)

Assigned Interventions

EXPERIMENTAL

The treatment regimen was HL-085 9mg BID+ Vemurafenib 720mg BID oral administration

Drug: HL-085+Vemurafenib

Interventions

HL-085+Vemurafenib DRUG

The treatment regimen was HL-085 9mg BID+ Vemurafenib 720mg BID oral administration for 21 days per cycle. The primary efficacy endpoint in this study was the ORR assessed by the Independent Review Committee (IRC) according to the RECIST 1.1

Assigned Interventions

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 18-75 (inclusive) at the time of signing the informed consent;
• Patients with locally advanced or metastatic stage IIIb, IIIc, or IV NSCLC (according to the AJCC Eighth Edition TNM staging system for lung cancer) who are confirmed by histopathology/cytology and cannot be resected by surgery can be included in the group without or after systemic treatment;
• At baseline, genetic testing reports of BRAF V600E mutation can be provided;
• The time interval between the end of the last anti-tumor therapy and the first administration of the study drug meets the following requirements: ≥4 weeks for cytotoxic drugs and cellular immunotherapy; PD-1/PD-L1/CTLA-4≥6 weeks; Small-molecule targeted drugs ≥2 weeks or 5 half-lives of drugs (whichever is longer); Mitomycin/nitrosourea ≥6 weeks; End time of radiotherapy ≥4 weeks (palliative local radiotherapy for pain relief ≥2 weeks), radiotherapy related adverse reactions recovered;
• ECOG PS score 0-1;
• Expected survival \> 3 months;
• At least one measurable lesion in line with the RECIST v1.1 definition at baseline (if the lesion at the site of previous radiotherapy is selected as the target lesion, this lesion has obvious evidence of progression);
• The level of organ function and related laboratory indicators must meet the following requirements:
• Neutrophil count absolute value (ANC) ≥ 1.5×109/L; Platelet count ≥ 100×109/L; Hemoglobin ≥ 90g/L;
• Blood biochemistry: serum total bilirubin ≤1.5 times the upper limit of normal value (ULN); For Gilbert syndrome patients, TBIL≤3×ULN; AST/ALT≤3 ULN (Allow AST/ALT≤5 ULN when liver metastasis occurs); Serum creatinine ≤1.5 ULN; Albumin ≥30 g/L;
• Coagulation: prothrombin time (PT) ≤ 1.5x ULN or activated partial thrombin time (APTT) ≤ 1.5x ULN;
• Creatine phosphokinase (CPK) and (hypersensitive) troponin (cTnI/T) are within normal ranges;
• The serum pregnancy test results of fertile women must be negative within 7 days prior to the first dosing, and female subjects are willing to use adequate contraception during the trial and for at least 6 months after the last dosing of the study drug. Male subjects must consent to use contraception (non-drug or tool contraception) for at least 6 months from the start of the study until the final dose;
• The subjects voluntarily participated in the study and signed the informed consent. The subjects had good compliance and could cooperate with the follow-up.

You may not qualify if:

• Patients who are known to have an allergic reaction to any BRAF and/or MEK inhibitors and their excipients or have an allergic predisposition;
• Patients with EGFR mutation, ALK fusion and other positive driver genes;
• Previous history of antitumor and surgical treatment conforms to any of the following:
• Being in the treatment phase of another clinical study within 4 weeks prior to initial dosing (except for patients participating in overall survival follow-up);
• Has undergone major surgery or has not fully recovered from previous invasive procedures within 4 weeks prior to initial dosing (other than baseline tumor biopsy);
• Previous use of MEK inhibitors, including but not limited to trametinib, smeitinib, caubitinib, pimetinib, and/or BRAF inhibitors, including but not limited to vermofinib, dalafenib, and Conefenib;
• Symptomatic or untreated brain metastases, meninges, or spinal cord compression (imaging instability, symptomatic lesion, need for hormonal or dehydration treatment); Subjects with asymptomatic and stable brain metastases (brain lesions ≥4 weeks stable without progression) could be enrolled;
• Pleural effusion, pericardial effusion and abdominal effusion that still cannot be controlled after clinical intervention;
• Patients with malignancies other than the type of tumor studied within 3 years prior to initial administration, except local cancers that have been apparently cured or have been free of disease for at least 3 years, such as basal or squamous cell skin cancer, superficial bladder cancer, prostate cancer in situ, cervical cancer in situ, or ductal carcinoma in situ of the breast;
• Patients who have previously received allogeneic bone marrow transplantation or organ transplantation;
• Previous or current retinal diseases, such as retinal venous obstruction (RVO), retinal arterial obstruction (RAO), retinal vasculitis, diabetic retinopathy, hypertensive retinopathy, retinal telangiectasis (Costs disease), retinal pigment epithelium detachment (RPED), etc.;
• Patients with past or current interstitial lung disease, including clinically significant radiation pneumonia (i.e. affecting activities of daily living or requiring intervention);
• Past or current neuromuscular diseases associated with elevated CPK (e.g., inflammatory myopathy, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy, rhabdomyolysis syndrome);
• Bleeding symptoms ≥ Grade 3 as defined in NCI CTCAE v5.0 occurred within 4 weeks prior to initial administration;
• Subjects with impaired heart function or clinically significant cardiovascular and cerebrovascular diseases, including any of the following:

Sponsors & Collaborators

• Shanghai Kechow Pharma, Inc.: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Yuankai Shi, phD

  Cancer Hospital Chinese Academy of Medical Science

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhimei Zhu, Master

CONTACT

15201345822; zhuzm@kechowpharma.com

Yuankai Shi, phD

CONTACT

+86-010-87788293; syuankaipumc@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2023
• First Posted: June 12, 2023
• Study Start: September 24, 2023
• Primary Completion: September 24, 2025
• Study Completion: September 24, 2025
• Last Updated: June 12, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share