A Phase II/III Clinical Study to Evaluate HLX07 in Combination With Serplulimab and Chemotherapy Versus Placebo in Combination With Serplulimab or Pembrolizumab and Chemotherapy as First-Line Treatment in Advanced Squamous Non-Small Cell Lung Cancer

2. Known EGFR-sensitizing mutation, ALK/ROS1 gene rearrangement, or other actionable driver oncogenes for which there are locally approved targeted first-line therapies.

Note: If the EGFR, ALK, ROS1 and other actionable driver oncogenes statuses are unknown, testing is not mandatory, unless there are high-risk factors (such as non-smoking female patients), under which circumstances testing of EGFR and other mutations may be considered.

3. Other malignancies within 5 years or active. Patients with localized tumors that have been cured, such as basal cell carcinoma, squamous-cell skin cancer, superficial bladder carcinoma, prostate carcinoma in situ, cervical carcinoma in situ, and breast cancer in situ, are eligible.

4. Scheduled or previous organ or bone marrow transplantation.

5. Uncontrollable pleural effusion, pericardial effusion, or ascites.

6. Active central nervous system (CNS) metastases and/or carcinomatous meningitis known or diagnosed at screening. However, the following patients may be enrolled:

* Patients with asymptomatic brain metastases (i.e., no progressive central nervous system symptoms caused by brain metastases, no requirement for glucocorticoid therapy, and lesion size ≤ 1.5 cm) may be enrolled, but are required to receive regular brain imaging as a site of lesion.

* Patients with treated brain metastases that have been stable for at least 1 month, with no evidence of new or enlarging brain metastases, and with glucocorticoid discontinued ≥ 3 days prior to randomization.

Stable brain metastases should be confirmed before randomization.

7. Spinal cord compression that has not been cured with radical surgery and/or radiotherapy.

8. Clinically significant hemoptysis complicated with superior vena cava syndrome.

9. Myocardial infarction and poorly controlled arrhythmia (including QTc intervals ≥ 450 ms for males and ≥ 470 ms for females) (QTc intervals are calculated by Fridericia's formula) within 6 months prior to randomization;

10. NYHA Class III-IV cardiac insufficiency or left ventricular ejection fraction (LVEF) \< 50% by echocardiography.

11. Inadequately controlled hypertension (defined as systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 100 mmHg), with a history of hypertensive crisis or hypertensive encephalopathy.

12. Grade ≥ 2 peripheral neuropathy as per CTCAE 6.0.

13. Human immunodeficiency virus (HIV) infection.

14. Active pulmonary tuberculosis.

15. A history of or active interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, or severe lung function impairment that may interfere with the detection and management of suspected drug-related pulmonary toxicity.

16. Known active or suspected autoimmune diseases. Patients with a history of autoimmune disease that does not require systemic immunosuppressive therapy for at least 12 months prior to screening are allowed to be enrolled.

17. Treatment with live vaccines within 28 days prior to randomization. Inactivated seasonal influenza vaccines and COVID-19 vaccines are allowed, but live attenuated influenza vaccines for intranasal use are not allowed.

18. Treatment with systemic glucocorticoids (\> 10 mg/day prednisone efficacy dosage) or other immunosuppressive drugs required within 14 days prior to randomization or during the study. However, patients are allowed to be enrolled under the following conditions: in the absence of active autoimmune disease, patients are allowed to use topical or inhaled glucocorticoids and adrenal glucocorticoid replacement therapy at a dose equivalent to ≤ 10 mg/day of prednisone efficacy.

19. Any active infection requiring systemic anti-infective therapy or use of systemic anti-infective therapy within 14 days prior to randomization.

20. Major surgery within 28 days prior to randomization; major surgery in this study is defined as any surgery that requires at least 3 weeks of postoperative recovery time before receiving the study treatment. Patients with a history of tumor needle biopsy or lymph node incisional biopsy are allowed to be enrolled.

21. Radical radiotherapy within 3 months prior to randomization. Note: Palliative radiotherapy to bone or palliative radiotherapy to superficial lesions is allowed according to the local treatment guidelines, which should have been completed 2 weeks prior to randomization. Radiotherapy covering more than 30% of the bone marrow area within 28 days prior to randomization is not allowed.

22. Prior use of other antibodies/drugs against immune checkpoints, such as PD-1, PD-L1, CTLA4, etc. Patients with prior systemic anti-EGFR monoclonal antibody therapy.

23. Current participation in any other clinical study, or the end of the previous clinical study treatment is less than 14 days apart from the planned start of the study treatment in this study.

24. Known history of severe allergy to any monoclonal antibody.

25. Known allergy to any components of carboplatin or paclitaxel (or nab-paclitaxel).

26. Pregnant or lactating women.

27. Known history of psychotropic abuse or drug abuse; history of alcohol abuse.

28. Presence of any other factors that may lead to a premature study discontinuation as judged by the investigator.

What this study is about