First-Line Therapy for Locally Advanced or Metastatic Squamous Non-Small Cell Lung Cancer (NSCLC) MedDRA version: 21.1 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: HLX10
Product Code: HLX10
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: not available
Current Sponsor code: HLX10
Other descriptive name: HLX10
Concentr
Sponsors
Shanghai Henlius Biotech, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Voluntary participation in the clinical study; fully aware and informed of the study and sign the Informed Consent Form (ICF); willing to comply with and able to complete all trial procedures. 2. Male or female at least 18 years old (inclusive) at the time of signing the ICF. 3. Patients with histologically or cytologically confirmed stage IIIB/IIIC or stage IV (AJCC Edition 8) squamous NSCLC where surgery or radiotherapy cannot be performed. 4. No known sensitizing EGFR mutations, ALK, ROS1 gene rearrangements. Note: Patients with known EGFR mutations, ALK, ROS1 rearrangements will be excluded; if EGFR, ALK, ROS1 status is unknown, testing of mutations such as EGFR may be considered if there are high risk factors (e.g. non-smoking female patients). 5. Patients who have not received systemic therapy for stage IIIB/IIIC or stage IV NSCLC. For patients who have received adjuvant or neoadjuvant therapy, if adjuvant/neoadjuvant therapy was completed at least 6 months prior to the diagnosis of stage IIIB/IIIC or stage IV NSCLC, the enrollment will be permitted. 6. Previous non-systematic anti-tumor treatment should be completed =2 weeks prior to the initiation of study medication, and treatment related AEs have returned to =grade 1 based on Common Terminology Criteria for Adverse Events (CTCAE) 5.0 (except grade 2 hair loss). 7. Within 4 weeks prior to randomization, there should be at least one measurable target lesion assessed by IRRC in accordance with the requirements of RECIST 1.1. Note: Measurable target lesions cannot be selected from sites that have been previously irradiated with the following exception. If no alternative lesion can be used as target lesion, the investigator should provide the before and after imaging data showing significant progression of the lesion after the completion of radiotherapy. 8. Patients must provide tumor tissues that meet the requirements for the determination of PD-L1 expression levels. Note: Formalin-fixed tumor tissue samples collected within 6 months prior to the first dose of study drug is recommended. Paraffin embedded tumor specimens (preferred) or unstained fresh serial sections (adhesion slides preferred). Relevant pathological report of the aforementioned specimens must also be provided. Freshly collected specimens, resection, core needle biopsy, excision, incision, punch or forceps biopsies are within acceptable range (newly obtained tissue preferred). Samples collected by needle aspiration (i.e., samples without complete tissue structure that are only provided for cell suspension and/or cell smear), brushing samples, and precipitated cell samples that come from pleural or peritoneal effusion are not acceptable. Refer to the laboratory’s operating manual for details on the tissue sample requirements. 9. The ECOG PS score should be 0 or 1 within 7 days prior to the first dose of study drug. 10. Expected survival =12 weeks. 11. Major organs are functioning well - please see the relevant criteria in the protocol (have not received transfusion, albumin, recombinant human thrombopoietin or colony-stimulating factor [CSF] therapy within 14 days prior to the first dose of study drug): 12. Female patients must meet the following: i. Menopause (defined as absence of menstrual period for at least 1 year and no other confirmed causes other than menopause), or ii. Have undergone sterilization operation (removal of ovaries and/or uterus), or iii. Have child-bearing potential, but must meet the fol
Exclusion criteria
Exclusion criteria: 1. Patients with histologically non-squamous NSCLC. Mixed tumors will be classified according to the primary cell type. Patients are not eligible if small cell components and neuroendocrine carcinoma components are present in the cancer tissue. For non-small cell histology, patients are eligible if squamous components (e.g., adenosquamous) are present. 2. Patients who have other concurrent malignancy within the past 5 years. Patients with cured localized tumors, such as basal cell carcinoma, cutaneous squamous cell carcinoma, superficial bladder cancer, prostate carcinoma in situ, cervical carcinoma in situ and ductal carcinoma in situ, are eligible. 3. Patients who are preparing to undergo or have undergone organ or hematopoietic stem cell transplantation. 4. Patients with uncontrollable pleural effusion, pericardial effusion, or ascites. 5. Patients who have known or active central nervous system (CNS) metastases and/or carcinomatous meningitis during the screening period. 6. Patients with spinal cord compression that cannot be cured by surgery and/or radiotherapy. 7. Patients with significant hemoptysis per the investigator, and concomitant superior vena cava syndrome. 8. Patients with myocardial infarction, or poorly controlled arrhythmia (including QTc interval =450 ms for males, =470 ms for females) (QTc interval is calculated using the Fridericia formula) within 6 months prior to the first dose of study drug; 9. Class III - IV cardiac insufficiency or echocardiogram in accordance with the New York Heart Association (NYHA) standards: left ventricular ejection fraction (LVEF) 10 mg/day therapeutic dose of prednisone) or other immunosuppressive drugs within 14 days prior to the first dose of study drug or during the study period. However, enrollment is permitted for the following situations: In absence of active autoimmune disease, patients are allowed to use topical or inhaled glucocorticoids and =10 mg/day therapeutic dose of prednisone for adrenal glucocorticoid replacement therapy. 19. Any active infection requiring systemic a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the clinical efficacy of HLX10 + chemotherapy vs chemotherapy as first-line therapy in patients with locally advanced or metastatic squamous NSCLC;Secondary Objective: To compare the safety of HLX10 + chemotherapy vs chemotherapy as first-line therapy in patients with locally advanced or metastatic squamous NSCLC. To evaluate pharmacokinetics (PK), immunogenecity and biomarker;Primary end point(s): Primary Efficacy Endpoint • Progression-free survival (PFS) (assessed by the independent radiology review committee [IRRC] based on Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) ;Timepoint(s) of evaluation of this end point: As assessed by the independent radiology review committee. The final analysis will occur at approximately 2 years from FPI. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints • Overall survival (OS) • PFS (assessed by the investigator based on RECIST 1.1) • PFS assessed by the IRRC and the investigator based on a modified RECIST 1.1 for immune-based therapeutics (termed iRECIST) • Objective response rate (ORR) (assessed by the IRRC and investigator based on RECIST 1.1) • Duration of response (DOR) (assessed by the IRRC and the investigator based on RECIST 1.1) • Quality of life assessment Safety Endpoints • Adverse events (AEs) (including serious adverse events [SAEs]), laboratory tests (routine blood test, blood chemistry, coagulation function, urinalysis, thyroid function, cardiac function), 12-lead electrocardiogram (12 lead ECG), vital signs, and physical examination, etc. PK Endpoint • Concentration of HLX10 in serum Immunogenicity Endpoint • HLX10 anti-drug antibody (ADA) positive rate Biomarker Endpoint • Relationship between PD-L1 expression, microsatellite instability (MSI), tumor mutation burden (TMB) in tumor tissue and efficacy ;Timepoint(s) of evaluation of this end point: OS – occur around 3 years after study start PFS – As assessed by the investigator based on RECIST 1.1 every 6 weeks (±7 days) within 48 weeks prior to the treatment period, and every 12 weeks (±7 days) PFS - As assessed by the IRRC and the investigator after 48 weeks. ORR – As assessed by the IRRC and investigator based on RECIST 1.1 every 6 weeks (±7 days) within 48 weeks prior to the treatment period, and every 12 weeks (±7 days) after 48 weeks. DOR – As assessed by the IRRC and investigator based on RECIST 1.1 every 6 weeks (±7 days) within 48 weeks prior to the treatment period, and every 12 weeks (±7 days) after 48 weeks. | — |
Countries
Brazil, China, Georgia, Italy, Poland, Russian Federation, Turkey, Ukraine, United States
Contacts
Public ContactWenying Kang
Shanghai Henlius Biotech, Inc.
Outcome results
None listed