Evaluating HLX208 and HLX10 for advanced lung cancer with BRAF V600E mutation

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.

This study is testing a new combination of two drugs to see if they can help people with advanced lung cancer that has a specific genetic mutation feel better and improve their treatment outcomes.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 49 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Shanghai Henlius Biotech (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation, prednisone
• Locations: 1 site (Shanghai)
• Trial ID: NCT05641493 on ClinicalTrials.gov

What this trial studies

This clinical trial is an open-label, multicenter phase Ib/II study aimed at assessing the safety, tolerability, pharmacokinetics, and efficacy of HLX208, a BRAF V600E inhibitor, in combination with HLX10, an anti-PD-1 monoclonal antibody, for patients with advanced non-small cell lung cancer (NSCLC) harboring the BRAF V600E mutation. In the phase Ib portion, two dose levels of HLX208 will be administered orally, while HLX10 will be given intravenously every three weeks. The phase II portion will continue with the recommended phase II dose of HLX208 alongside HLX10. The study seeks to provide insights into the effectiveness of this combination therapy in a specific patient population.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 80 with advanced NSCLC and a confirmed BRAF V600E mutation who have previously failed standard therapies.

Not a fit: Patients without the BRAF V600E mutation or those who are not advanced NSCLC cases may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with advanced NSCLC with the BRAF V600E mutation.

How similar studies have performed: Other studies have shown promising results with similar combinations of targeted therapies and immunotherapies, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. ≥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.
2. Signed written informed consent.
3. 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%).
4. Previous failure of standard therapy, intolerance to standard therapy, lack of standard therapy, or currently unsuitable for standard therapy.
5. 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)
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
7. Expected survival time ≥ 3 months.
8. At least one measurable target lesion per RECIST v1.1 (brain metastasis could not be considered as the only measurable lesion).
9. 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).
10. 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
11. Fertile subjects (male or female) must agree to take effective contraceptive measures from the time of signing the ICF until 90 days after the last dose of HLX208 or 6 months after the last dose of HLX10. Female subjects of childbearing potential must complete a pregnancy test with a negative result within 7 days prior to the first dose.

Exclusion Criteria:

1. 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.
2. Known EGFR mutations or ALK rearrangements (except in subjects with EGFR mutations whose disease has progressed after previous EGFR inhibitor treatment).
3. Received strong CYP3A inhibitors or inducers treatment within 1 week prior to the first dose of investigational product.
4. 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.
5. With uncontrolled pleural effusion, pericardial effusion, or ascites.
6. 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).
7. 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.
8. With any serious infection requiring systemic anti-infective therapy within 14 days prior to the first dose of the investigational product.
9. 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.
10. 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.
11. Being positive (+) for HCV RNA.
12. Being positive (+) human immunodeficiency virus (HIV) antibody.
13. History of serious cardiovascular and cerebrovascular diseases.
14. Systemic treatment with corticosteroids (\> 10 mg/day prednisone or equivalent) or other immunosuppressive agents within 14 days prior to the first dose of the investigational product or during the study. In the absence of active autoimmune disease, subjects are allowed to use inhaled or topical steroids, or adrenal hormone replacement therapy at an effective dose equivalent to ≤10 mg/day prednisone.
15. Known active or suspected autoimmune diseases. Subjects with autoimmune related hypothyroidism receiving thyroid hormone replacement therapy are allowed to participate in the study. Subjects with stable type 1 diabetes receiving insulin therapy are allowed to participate in the study.
16. Known alcohol of or drug abuse.
17. Pregnant or lactating women.
18. Received live vaccine within 28 days prior to the first dose of investigational product.
19. Have other conditions not suitable for inclusion as judged by the investigator.

Where this trial is running

Shanghai

• Shanghai Chest Hospital, Shanghai Jiao Tong University, School of Medicine — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Shun Lu, Dr. — Shanghai Chest Hospital, Shanghai Jiao Tong University School Of Medicine
• Study coordinator: Shun Lu, Dr.

Conditions Non Small Cell Lung Cancer; HLX208; HLX10; BRAF V600E mutation