QL1706 Plus Anlotinib as a Later-line Treatment for Patients With Advanced Lung Cancer

A Multicenter, Open-label, Randomized Controlled Phase II/III Study Evaluating the Efficacy and Safety of QL1706 in Combination With Anlotinib as a Later-line Treatment for Patients With Advanced Lung Cancer

This is a multicenter, open-label, randomized controlled phase II/III study evaluating the efficacy and safety of QL1706 in combination with anlotinib as later-line treatment in patients with advanced lung cancer.

The study consists of four cohorts, each planning to enroll 30 subjects. Cohort 1 (advanced SCLC) and Cohort 3 (advanced squamous NSCLC) will receive later-line treatment with QL1706 5 mg/kg intravenously once every 3 weeks (Q3W) plus anlotinib 10 mg orally once daily (qd). Cohort 2 (advanced SCLC) and Cohort 4 (advanced squamous NSCLC) will receive anlotinib 10 mg orally once daily alone. Treatment continues until disease progression (and the investigator determines that the subject no longer derives clinical benefit) or other criteria for study treatment discontinuation are met, whichever occurs first.

Inclusion Criteria:

• 1. Male or female patients aged 18 years and above, up to 80 years old. 2. Small cell lung cancer or lung squamous cell carcinoma confirmed by tissue or pathological examination.

  3. Requires previous treatment with platinum-based drugs. 4. Requires previous treatment with PD-1/PD-L1 drugs. 5. Patients must have received at least 2 lines of treatment, no more than 3 lines of treatment.

  6. Confirmed as small cell lung cancer by histological examination. 7. Able to provide informed consent and comply with the trial protocol. 8. According to RECIST 1.1 standards, there are measurable lesions (CT scan). 9. Expected lifespan ≥ 12 weeks. 10. ECOG performance status 0-1. 11. Patients must have adequate organ and bone marrow functions, defined as follows:

  1. Absolute neutrophil count ≥ 1,500/mcL

  2. Platelet count > 90,000/mcL

  3. Hemoglobin ≥ 9 g/dL (allowing for Hgb transfusion)

  4. Creatinine ≤ 1.5 × ULN

  5. Total bilirubin ≤ 1.5 mg/dL or ≤ 26 μmol/L

  6. If there is liver metastasis, AST (SGOT) / ALT (SGPT) ≤ 5 × ULN; if there is no liver metastasis, ≤ 2.5 × ULN

  7. Albumin ≥ 2.5 g/dL 12. Patients are allowed to receive palliative radiotherapy (such as radiotherapy after brain metastasis), provided that there are measurable target lesions in the radiation field of the patient.

     13. Able to go to the research center to ensure that patients complete all research-related appointments.

     14. Pregnant women and male partners of pregnant women must agree to take adequate contraceptive measures (hormonal or barrier methods; abstinence) before entering the study, during the study, and within 90 days after completing the study (hormonal or barrier methods; abstinence). If a woman becomes pregnant during the study or suspects she is pregnant, she should immediately inform the attending doctor.

     Note: Pregnant women are defined as any woman meeting the following criteria (regardless of sexual orientation, whether tubal ligation has been performed or being single):

  1. No hysterectomy or bilateral oophorectomy;

  2. No natural menopause for at least 12 consecutive months (i.e., any time during the previous 12 months there was menstruation).

     Exclusion Criteria:

• 1. Patients with symptomatic central nervous system metastases, or those with unstable neurological symptoms requiring an increase in the dosage of corticosteroids.

  2. Presence of another primary malignant tumor (excluding cervical carcinoma in situ or skin basal cell carcinoma).

  3. The patient has a clinically significant disease that affects their participation in this study, including but not limited to: active or uncontrolled infection, SARS-CoV-2 infection, immunodeficiency, hepatitis B, hepatitis C, uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled arrhythmia, QTc interval prolongation > 450 ms or a mental illness/socioeconomic condition that limits their compliance with the study requirements.

  4. Previous use of CTLA-4 monotherapy or combination antibodies containing CTLA-4.

  5. Previous treatment with anti-angiogenic drugs. 6. Presence of uncontrolled or symptomatic pleural or pericardial effusion, etc.

  7. Uncontrolled or clinically significant third-space effusion. 8. Severe adverse reactions occurred during previous immunotherapy, and the investigator considers it unsuitable for re-administration of immunotherapy.

  9. Any condition that may interfere with the subject's participation in the study or the evaluation of the study results.

  10. Receiving major surgery within 30 days before the first day of the study. 11. Currently using or expected to use within 14 days before the first administration of drugs or foods known to be potent CYP3A4/5 inhibitors or CYP3A4/5 inducers (such as grapefruit juice or grapefruit/grapefruit-related citrus fruits (such as oranges, grapefruits), ketoconazole, miconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, indinavir, saquanavir, ritonavir, nelfinavir, amprenavir, fosamprenavir, nefazodone, lopinavir, ritonavir), and applying these drugs locally (such as 2% ketoconazole cream is allowed);