QL1706 plus chemotherapy for immune-resistant advanced NSCLC

A Randomized Controlled Study Comparing the Efficacy of QL1706 Combined With Chemotherapy in the Treatment of Immune-mediated Non-small Cell Lung Cancer

This trial tests whether adding QL1706 to chemotherapy helps people with advanced non-small cell lung cancer who are EGFR/ALK negative and whose cancer progressed after prior PD‑1/PD‑L1 plus platinum therapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 96 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Anhui Provincial Cancer Hospital (other)
• Drugs / interventions: chemotherapy, prednisone, Iparomlimab, Tuvonralimab, immunotherapy
• Locations: 1 site (Hefei)
• Trial ID: NCT07330596 on ClinicalTrials.gov

What this trial studies

This is a randomized, open-label Phase 2 trial enrolling 96 patients with locally advanced or recurrent/metastatic NSCLC lacking EGFR or ALK driver mutations who progressed after first-line PD‑1/PD‑L1 plus platinum therapy. Participants are randomized 1:1 to receive QL1706 combined with docetaxel or gemcitabine versus docetaxel or gemcitabine alone. The trial uses measurable RECIST v1.1 tumor responses and safety outcomes to compare the combination versus chemotherapy alone. The protocol requires ECOG 0–2 and an expected survival of at least 12 weeks, with contraception and pregnancy testing for women of childbearing potential.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically or cytologically confirmed locally advanced or metastatic NSCLC, negative for EGFR and ALK alterations, who progressed after prior PD‑1/PD‑L1 plus platinum first-line therapy, have at least one measurable lesion, ECOG 0–2, and expected survival ≥12 weeks are the intended candidates.

Not a fit: Patients with known EGFR or ALK driver mutations, poor performance status (ECOG >2), uncontrolled comorbidities, or those who cannot attend required site visits or use contraception as mandated are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, adding QL1706 could increase tumor response rates and extend disease control compared with chemotherapy alone for this group of previously treated patients.

How similar studies have performed: Combinations of immune checkpoint inhibitors with chemotherapy and PD‑1 plus CTLA‑4 strategies have shown benefit in NSCLC in prior trials, but QL1706 itself is a newer agent with limited published data compared with established agents.

Eligibility criteria

Inclusion Criteria:

* Voluntarily participate in the research and sign an informed consent form; Age ≥ 18 years old, ≤ 75 years old;
* Diagnosed with NSCLC through histology or cytology;
* No EGFR sensitive mutations or ALK gene translocation changes;
* Previously received PD-1/PD-L1 inhibitors combined with platinum based dual therapy or sequential therapy as first-line treatment for advanced metastatic or recurrent NSCLC, and disease progression occurred during or after treatment; At least one measurable lesion should be used as the target lesion (RECIST v1.1 standard);
* ECOG score: 0-2 points;
* Expected survival period is not less than 12 weeks;
* Women of childbearing age must undergo a pregnancy test (serum or urine) with a negative result within 28 days before enrollment, and voluntarily use appropriate contraception methods during the observation period and within 8 weeks after the last dose; For males, surgical sterilization or consent to use appropriate contraception methods during the observation period and within 8 weeks after the last dose should be provided;
* The laboratory test results during the screening period indicate that the patient has good organ function: a) Hematology (no blood transfusion within 14 days and no treatment with blood components or granulocyte colony-factor): Neutrophil count (NEU) ≥ 1.5 × 10 \^ 9/L (1500/mm3); Platelet count (PLT) ≥ 100 × 10 \^ 9/L (100000/mm3); Hemoglobin ≥ 90 g/L; b) Liver: serum total bilirubin (TBil) ≤ ULN; Glutamate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 × ULN; AST or ALT should be 1.5-3.5 × ULN, and alkaline phosphatase (ALP) should be ≤ 2.5 × ULN; c) Kidney: creatinine clearance rate (CrCl) calculated value ≥ 30 mL/min; d) Coagulation function: International normalized ratio (INR) ≤ 1.5, and prothrombin time (PT) or activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; j) International Normalized Ratio (INR) ≤ 1.5; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN;
* Patients whom researchers believe can benefit.

Exclusion Criteria:

* There are EGFR sensitive mutations or ALK gene translocation changes present;
* Previously received PD1/CTLA4 bispecific antibody therapy;
* Adverse reactions caused by previous treatment have not recovered to CTCAE (version 5.0) grade 1 or below (excluding toxicity ≤ grade 2 that has been determined by the researcher to exist for a long time, cannot be recovered, and does not increase safety risks);
* Symptomatic central nervous system metastasis. Patients who have received treatment for brain metastases and have been deemed stable by researchers may consider participating in this study;
* For patients with poor control of cancer-related pain, those who require analgesic treatment must receive a stable dose of treatment before participating in the study;
* Chest fluid, ascites or pericardial effusion with clinical symptoms or unstable condition after symptomatic treatment;
* Known to have a history of severe allergic reactions to the drug and its components, planned chemotherapy drugs, and those with a history of severe allergic reactions;
* Suffering from or suspected of active autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory intestinal diseases, etc., except: type I diabetes and hypothyroidism that can be controlled through stable dose replacement treatment, and skin diseases that do not require systemic treatment (such as psoriasis, vitiligo);
* History of interstitial lung disease or drug-induced interstitial lung disease or pneumonia in the past;
* Corticosteroid drugs (prednisone\>10mg/day or equivalent dose) or other immunosuppressive drugs received systemically within 14 days prior to the first study medication;
* Individuals with a history of immunodeficiency, including those with other acquired or congenital immunodeficiency diseases, those with a history of organ transplantation, or those who have received allogeneic hematopoietic stem cell transplantation or solid organ transplantation; Received live vaccination within 4 weeks before the first study medication;
* Suffering from serious cardiovascular and cerebrovascular diseases: a) poorly controlled hypertension or pulmonary arterial hypertension; b) Unstable angina or myocardial infarction, coronary artery bypass grafting or stent implantation within 6 months prior to study medication; c) Chronic heart failure with heart function ≥ 2 (NYHA classification by the New York Heart Association); d) Left ventricular ejection fraction (LVEF)\<50%; e) Various severe arrhythmias requiring medication treatment (excluding atrial fibrillation or paroxysmal supraventricular tachycardia). For example, male QTcF\>450 milliseconds or female QTcF\>470 milliseconds, complete left bundle branch block, grade III block; f) Cerebrovascular accident (CVA) or transient ischemic attack (TIA) occurred within 6 months prior to the study medication;
* Positive result of human immunodeficiency virus (HIV) antibody test, active hepatitis B or C. The following conditions are allowed to participate in this study: a) hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg) is positive, but HBV DNA is lower than the lower limit of the detection value of the research center (negative) or less than 500IU/ML, and the active infection is excluded according to the judgment of the researcher based on clinical treatment and performance; b) Individuals with positive hepatitis C antibodies and HCV RNA below the lower limit (negative) of the detection value at the research center;
* Suffering from other active malignant tumors other than the research disease within 5 years, except for malignant tumors that can be expected to recover after treatment (including but not limited to fully treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell carcinoma, or breast ductal carcinoma in situ treated with radical surgery);
* Individuals with a history of substance abuse and inability to quit, or those with a history of mental disorders;
* Pregnant or lactating women;
* The researcher believes that the patient is not suitable to participate in any other circumstances of this study.

Where this trial is running

Hefei

• Anhui cancer hospital — Hefei, China (RECRUITING)

Study contacts

• Study coordinator: Shuanghu-Yuan Professor Yuan, M.D.

Conditions: NSCLC, Immune resistance, PD-1/CTLA-4, EGFR/ALK Mutation Negative