A Study of QL1706 in Combination With Chemotherapy in PD-L1-Negative Non-small Cell Lung Cancer

A Randomized, Double-blind, Multicenter Phase 3 Clinical Study to Evaluate the Efficacy and Safety of QL1706 in Combination With Chemotherapy in First-line PD-L1 Negative, Locally Advanced or Metastatic Non-small Cell Lung Cancer Patients

The purpose of this study is to evaluate the efficacy and safety of QL1706 combined with platinum-based chemotherapy versus tislelizumab combined with platinum-based chemotherapy in PD-L1 negative, locally advanced or metastatic Non-small Cell Lung Cancer Patients. The subjects were randomly divided into two groups according to 1:1, with about 304 subjects in the experimental group and the control group.

Study Overview

• Status: Active, not recruiting
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: QL1706; Drug: Tilesizumab

Detailed Description

This study was a randomized, double-blind, active-controlled, multicenter Phase 3 clinical study. The study is designed to evaluate the efficacy and safety of QL1706 in combination with chemotherapy or commercial PD1 in combination with chemotherapy in locally advanced or metastatic NSCLC patients who are PD-L1 negative.608 patients would be enrolled . Subjects will be assigned randomly in a 1:1 ratio to experimental group and control group. Subjects will be stratified by pathological type: squamous cell carcinoma versus non-squamous cell carcinoma; brain metastasis: present versus absent; gender: male versus female. After randomization, subjects will be treated according to the randomization results.

• Study Type: Interventional
• Enrollment (Actual): 606
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be≥18 to ≤ 75 years of age at enrollment, male or female.
2. Histologically or cytologically confirmed locally advanced (Stage IIIB/IIIC) that not amenable to complete surgical resection and not amenable to radical concurrent/sequential chemoradiation or metastatic (Stage IV) NSCLC (American Joint Committee on Cancer [AJCC] 8th edition).
3. No EGFR sensitive mutations or ALK gene translocation alterations.
4. Capable of providing fresh or archived 2 years' tissue samples collected at post-diagnosis or non-radiation sites at diagnosis for central laboratory PD-L1 testing with TPS < 1% .
5. Have a life expectancy of at least 3 months.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. No prior systemic therapy for advanced or metastatic NSCLC was received.

Exclusion Criteria:

1. Previous treatment with immune checkpoint inhibitors (PD-1/PD-L1 drugs or drugs acting on another T cell receptor (e.g., CTLA-4 etc.), as well as immune checkpoint agonistic antibodies (e.g., anti ICOS , CD40 , CD137 , GITR , OX40 antibodies, etc.), and immune cell therapy.
2. Patients who have received systemic corticosteroids or other immunosuppressive drugs within 2 weeks prior to the first dose.
3. Presence or history of any active autoimmune disease, including, but not limited to: autoimmune hepatitis, interstitial pneumonia, pulmonary fibrosis, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism.
4. Pulmonary radiation therapy > 30 Gy within 6 months prior to first dose;
5. Palliative radiotherapy completed 7 days prior to first dose.
6. Known or symptomatic active central nervous system (CNS) metastases or carcinomatous meningitis during screening.

7. Clinically significant cardiovascular or cerebrovascular disease

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QL1706+chemotherapy; Participants with locally advanced or metastatic NSCLC patients who are PD-L1 negative will receive QL1706, paclitaxel/pemetrexed and carboplatin by intravenous (IV) injection on Day 1 of each 21-day cycle for 4 cycles in the induction treatment. In the maintenance phase, participants will be treated with QL1706 or QL1706 combined with pemetrexed.	Drug: QL1706; QL1706 will be administered by IV infusion at 5mg/kg on Day 1 of each 21-day cycle until unacceptabletoxicity or loss of clinical benefit.; Other Names: PSB205
Active Comparator: Tiselizumab+chemotherapy; Participants with locally advanced or metastatic NSCLC patients who are PD-L1 negative will receive tiselizumab, paclitaxel/pemetrexed and carboplatin by intravenous (IV) injection on Day 1 of each 21-day cycle for 4 cycles in the induction treatment. In the maintenance phase, participants will be treated with tiselizumab or tiselizumab combined with pemetrexed.	Drug: Tilesizumab; Tilesizumab will be administered by IV infusion at 200mg on Day 1 of each 21-day cycle until unacceptabletoxicity or loss of clinical benefit.; Other Names: BGB-108

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall Survival (OS) in the ITT population determined by the investigator	From date of randomization until the date of death from any cause, which ever came first, assessed up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression Free Survival in the intent to treat (ITT) population, as determined by the investigator according to RECIST v1.1 criteria	Informed consent until disease progression or death, which ever occurs first (up to approximately 2 years)
ORR	Objective Response Rate assessed by investigator according to RECIST v1.1 criteria	First administration until disease progression or death, which ever occurs first (up to approximately 24 months)
DOR	Duration of Response assessed by investigator according to RECIST v1.1 criteria	First administration until disease progression or death, which ever occurs first (up to approximately 24 months)
DCR	Disease Control Rate assessed by investigator according to RECIST v1.1 criteria	First administration until disease progression or death, which ever occurs first (up to approximately 24 months)

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Li Zhang, Professor, Sun Yat-sen Univeisity Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2023
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: January 10, 2023
• First Submitted That Met QC Criteria: January 10, 2023
• First Posted (Actual): January 19, 2023

Study Record Updates

• Last Update Posted (Estimated): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: QL1706-303

Drug and device information, study documents

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