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.

Study Overview

• Status: Not yet recruiting
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: QL1706; Drug: Anlotinib

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Yan Huang, MD; Email: huangyan@sysucc.org.cn
• Study Contact Backup: Name: Li Zhang, MD; Phone Number: +86-20-87343289; Email: zhangli@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cohort 1; Cohort 1 includes patients with advanced SCLC who have received at least 2 lines of treatment but no more than 3 lines of treatment in the past.	Drug: QL1706; Every 3 weeks, 5mg/kg of QL1706 is administered intravenously until the disease progresses.; Drug: Anlotinib; 10mg Anlotinib is administered orally. It is given daily for the first 14 days, then stopped for 7 days. A 3-week period constitutes one cycle, and this process continues until the disease progresses.
Active Comparator: cohort 2; Cohort 2 includes patients with advanced SCLC who have received at least 2 lines of treatment but no more than 3 lines of treatment in the past.	Drug: Anlotinib; 10mg Anlotinib is administered orally. It is given daily for the first 14 days, then stopped for 7 days. A 3-week period constitutes one cycle, and this process continues until the disease progresses.
Experimental: cohort 3; Cohort 3 includes patients with advanced lung squamous cell carcinoma who have received at least 2 lines of treatment but no more than 3 lines of treatment in the past.	Drug: QL1706; Every 3 weeks, 5mg/kg of QL1706 is administered intravenously until the disease progresses.; Drug: Anlotinib; 10mg Anlotinib is administered orally. It is given daily for the first 14 days, then stopped for 7 days. A 3-week period constitutes one cycle, and this process continues until the disease progresses.
Active Comparator: cohort 4; Cohort 4 includes patients with advanced lung squamous cell carcinoma who have received at least 2 lines of treatment but no more than 3 lines of treatment in the past.	Drug: Anlotinib; 10mg Anlotinib is administered orally. It is given daily for the first 14 days, then stopped for 7 days. A 3-week period constitutes one cycle, and this process continues until the disease progresses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival (OS), defined as the time from first study treatment to death from any cause.	From date of first study treatment to date of death from any cause, assessed up to approximately 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression-free survival (PFS) is defined as the time from the first trial treatment to disease progression or death due to any cause (whichever occurs first).	From date of first study treatment to the date of first documented disease progression or date of death from any cause, whichever occurs first, assessed up to approximately 36 months.
DCR	Disease Control Rate (DCR), the proportion of patients achieving the best overall therapeutic response of CR, PR or SD	From first study treatment to disease progression or initiation of new anti-tumor therapy, assessed up to approximately 36 months
12-months OS rate	The 12-month overall survival rate is defined as the proportion of patients who remain alive 12 months after the first trial treatment.	From date of first study treatment to date of death from any cause, assessed up to 12 months
Adverse Events	Incidence and severity of adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Relationship to study treatment (QL1706 and/or anlotinib) is assessed by the investigator.	From signing of informed consent through 90 days after the last dose of study treatment or initiation of new anti-tumor therapy, whichever occurs first.

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Li Zhang, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): July 30, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: June 4, 2026
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: small cell lung cancer; later-line
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma; anlotinib
• Other Study ID Numbers: SL-B2025-731-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD sharing was not included in the informed consent form approved by the ethics committee. Therefore, sharing individual participant data would violate the ethical agreements made with study participants.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No