A Phase Ib/II Clinical Trial to Evaluate the Safety and Efficacy of HLX208+HLX10 in NSCLC With BRAF V600E Mutation

Launched by SHANGHAI HENLIUS BIOTECH · Nov 30, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment combination for patients with advanced non-small cell lung cancer (NSCLC) that has a specific mutation called BRAF V600E. The treatment being tested includes two drugs: HLX208, which targets the BRAF mutation, and HLX10, which helps the immune system fight cancer. The trial aims to find out how safe these drugs are, how well they work, and how the body handles them.

To participate in this trial, candidates should be between 18 and 80 years old and have advanced NSCLC with the BRAF V600E mutation. They should have already tried standard treatments that did not work or were not suitable for them. Participants must be in good general health, able to take oral medications, and have measurable cancer that can be evaluated during the study. Throughout the trial, patients will receive the new treatment and be closely monitored for any side effects or improvements in their condition. It's important to note that some patients may not be eligible due to previous treatments or certain health conditions, so it's best to discuss this with a healthcare provider.

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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.

Trial Officials