A Phase Ib/II Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HLX208 （BRAF V600E Inhibitor） Combined With Serplulimab（HLX10, Anti-PD-1 Antibody） in Advanced NSCLC Patients With BRAF V600E Mutation.

Shanghai Henlius Biotech1 site in 1 country49 target enrollmentFebruary 28, 2023

ConditionsNon Small Cell Lung Cancer

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Non Small Cell Lung Cancer
Sponsor: Shanghai Henlius Biotech
Enrollment: 49
Locations: 1
Primary Endpoint: MTD (for phase Ib study)
Status: Recruiting
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

An open-label, multicenter phase Ib/II clinical study to evaluate safety, tolerability, pharmacokinetics, and efficacy of HLX208 (BRAF V600E Inhibitor) combined with HLX10 （anti-PD-1 monoclonal antibody）in advanced NSCLC patients with BRAF V600 mutation.

Detailed Description

This is an open-label, multicenter phase Ib/II clinical study to evaluate safety, tolerability, pharmacokinetics, and efficacy of HLX208 (BRAF V600E Inhibitor) combined with HLX10 （anti-PD-1 monoclonal antibody）in advanced NSCLC patients with BRAF V600 mutation. For the phase Ib study, HLX208 is administered orally at two dose levels of 600mg BID or 900 mg BID. And HLX10 is administered intravenously at a fixed dose of 300mg every 3 weeks. For the phase II study, HLX208 is administered orally with the RP2D dose. And HLX10 is administered intravenously at a fixed dose of 300mg every 3 weeks.

Registry

clinicaltrials.gov

Start Date

February 28, 2023

End Date

February 27, 2026

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shanghai Henlius Biotech

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•≥18 and ≤75 years old of age (in phase Ib study) or ≥18 and ≤80 years old of ag (in phase II study) at the time of informed consent.
•Signed written informed consent.
•BRAF V600E mutant advanced solid tumors (in phase Ib study) or advanced NSCLC (in phase II study) patients with positive PD-L1 expression (TPS or TC≥1%).
•Previous failure of standard therapy, intolerance to standard therapy, lack of standard therapy, or currently unsuitable for standard therapy.
•Prior systemic anti-neoplastic therapy (chemotherapy, radiotherapy, targeted therapy, or traditional Chinese medicine with anti-neoplastic indications) must have been ≥ 2 weeks from the first dose in this study with treatment-related AE resolved to NCI-CTCAE Grade ≤ 1 (except for alopecia)
•Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-
•Expected survival time ≥ 3 months.
•At least one measurable target lesion per RECIST v1.1 (brain metastasis could not be considered as the only measurable lesion).
•With normal major organ functions (no blood transfusions or treatment with colony-stimulating factor within 14 days prior to the first dose in this study).
•Be able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bow

Exclusion Criteria

•For subjects in phase II study: previous treatment with BRAF inhibitors or MEK inhibitors or previous treatment with T cell co-stimulation or immune checkpoint therapy.
•Known EGFR mutations or ALK rearrangements (except in subjects with EGFR mutations whose disease has progressed after previous EGFR inhibitor treatment).
•Received strong CYP3A inhibitors or inducers treatment within 1 week prior to the first dose of investigational product.
•Received major surgery within 28 days prior to the first dose of investigational product. A major surgery is defined as a surgery that takes at least 3 weeks of postoperative recovery before receiving treatment in this study.
•With uncontrolled pleural effusion, pericardial effusion, or ascites.
•With symptomatic brain or meningeal metastases (unless the patient has been treated for \>3 months, there is no evidence of progression on imaging within 4 weeks prior to the first dose, and the tumor-related clinical symptoms are stable).
•With active pulmonary tuberculosis. Patients with previous and current interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, or severe impaired pulmonary function that may interfere with the detection and management of suspected drug-related pulmonary toxicity.
•With any serious infection requiring systemic anti-infective therapy within 14 days prior to the first dose of the investigational product.
•History of other malignant tumors (except for cured carcinoma in situ of the cervical or basal cell carcinoma of the skin) within two years prior to the first dose of investigational product.
•Being positive (+) for hepatitis B surface antigen (HBsAg) or positive (+) for hepatitis B core antibody (HBcAb), and with hepatitis B virus deoxyribonucleic acid (HBV-DNA) ≥ 2500 copies/mL or 500 IU/mL.