A Phase II Study of QL1706 and Platinum-Based Chemotherapy in Patients With SMARCA4-Deficient, Locally Advanced or Metastatic Non-Small Cell Lung Cancer.

NCT07200947 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: NCC5684
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This single-arm, open-label, Phase II study assesses first-line QL1706 (iparomlimab and tuvonralimab, an anti-PD-1/CTLA-4 bispecific antibody) combined with platinum-based chemotherapy to treat patients with treatment-naïve, locally advanced or metastatic, SMARCA4-deficient non-small cell lung cancer (NSCLC). The main questions it aims to answer are:Evaluate the efficacy and safety of this combination regimen in this specific patient population. Explore correlations between tumor molecular characteristics, the immune microenvironment, and treatment efficacy or toxicity. Participants must: Have histologically or cytologically confirmed, treatment-naïve, locally advanced or metastatic non-small cell lung cancer (NSCLC) with SMARCA4 deficiency. Be willing to provide archived or fresh tumor tissue samples. If unavailable, enrollment may proceed per investigator assessment. Have at least one measurable lesion per RECIST v1.1.

Conditions

SMARCA4-Deficient Tumor; Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Keywords

QL1706; combination therapy; first line therapy; SMARCA4-Deficient Locally advanced or Metastatic Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS is defined as the time from the first dose of study treatment to the first documentation of disease progression according to RECIST v1.1 (as assessed by investigators) or death from any cause, whichever occurs first. Subjects who are alive without progression at the time of analysis will be censored at the date of the last tumor assessment.

  From enrollment to the end of monitoring at 2 years.

Secondary Outcomes (5)

• Overall Survival (OS)

  From enrollment to the end of monitoring at 2 years.

• Objective Response Rate (ORR)

  From enrollment to the end of monitoring at 2 years.

• Duration of Response (DoR)

  From enrollment to the end of monitoring at 2 years.

• Disease Control Rate (DCR)

  From enrollment to the end of monitoring at 2 years.

• The incidence of adverse events

  From enrollment to the end of monitoring at 2 years

Other Outcomes (1)

• Immune-Related Adverse Events (irAEs)

  From enrollment to the end of monitoring at 2 years

Study Arms (1)

combined treatment group

EXPERIMENTAL

This study evaluates a first-line treatment for locally advanced or metastatic SMARCA4-deficient non-small cell lung cancer (NSCLC), combining QL1706-a bifunctional antibody targeting both PD-1 and CTLA-4-with platinum-based chemotherapy (nab-paclitaxel + carboplatin). QL1706 is designed to provide dual immune checkpoint blockade with a optimized safety profile. This synergistic approach integrates immunotherapy and chemotherapy to address the high unmet need in this aggressive disease subset. Patients receive QL1706 monotherapy as maintenance treatment after 4-6 cycles of induction. No prior prospective studies have evaluated this regimen in SMARCA4-deficient NSCLC.

Drug: QL1706, nab-paclitaxel, carboplatin

Interventions

QL1706, nab-paclitaxel, carboplatin DRUG

Participants will receive QL1706 (5 mg/kg, IV, day 1) in combination with nab-paclitaxel (260 mg/m², IV, day 1) and carboplatin (AUC=4-5, IV, day 1) every 21 days for 4-6 cycles. Dose adjustments may be made based on clinical judgment. Patients who do not experience disease progression or intolerable toxicity will proceed to maintenance therapy with QL1706 (5 mg/kg, IV, day 1) every 21 days. Treatment will continue until disease progression, unacceptable toxicity, consent withdrawal, investigator decision, loss to follow-up, death, or meeting other protocol-defined criteria for discontinuation. The maximum duration of QL1706 treatment is 24 months, after which continuation will be at the investigator's discretion based on individual benefit-risk assessment.

combined treatment group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria to be eligible for the study:
• Voluntary participation and provision of signed written informed consent.
• Age ≥ 18 years.
• Life expectancy ≥ 3 months.
• Histologically or cytologically confirmed diagnosis of Stage IIIB-IV lung cancer that is not amenable to curative surgery or radiotherapy.
• Tumor demonstrates loss of BRG1 protein (encoded by the SMARCA4 gene) as confirmed by immunohistochemistry (IHC).
• No prior systemic anti-cancer therapy for advanced disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Willingness to provide archived or fresh tumor tissue samples from primary or metastatic lesions. If unavailable, enrollment may be permitted following investigator assessment.
• At least one measurable lesion as defined by RECIST v1.1.
• Adequate organ function within the screening period, as evidenced by:
• Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L 10.2 Platelet count ≥ 100 × 10\^9/L 10.3 Hemoglobin ≥ 90 g/L (without transfusion within 14 days) 10.4 Serum creatinine ≤ 1 × ULN OR Creatinine clearance \> 50 mL/min (calculated by Cockcroft-Gault formula) 10.5 AST and ALT ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastases) 10.6 Total bilirubin ≤ 1.5 × ULN (except for participants with Gilbert's syndrome) 10.7 TSH, FT3, and FT4 within normal limits (±10%)

You may not qualify if:

• Participants meeting any of the following criteria will be excluded from the study:
• Pathological diagnosis containing a small cell component.
• Symptomatic brain metastases.
• Leptomeningeal metastases.
• Recurrence within 6 months after completing prior adjuvant therapy (if applicable).
• Active, known, or suspected autoimmune disease (with specific exceptions, e.g., vitiligo, type I diabetes, hypothyroidism managed with hormone replacement only).
• Active tuberculosis (TB) infection or history of active TB within the past year.
• Comorbidities requiring immunosuppressive medications, including systemic corticosteroids at immunosuppressive doses.
• Pregnancy or lactation in female participants.
• Symptomatic interstitial lung disease that could interfere with the detection or management of suspected drug-related pulmonary toxicity.
• Known HIV infection, active Hepatitis B (HBsAg positive with HBV-DNA \> 10\^3 copies/mL), or active Hepatitis C (HCV antibody positive with detectable HCV-RNA).
• Significant history of neurological or psychiatric disorders.
• Treatment with any investigational drug within 4 weeks prior to the first dose of study treatment.
• Use of Chinese herbal medicines with anti-tumor activity within 2 weeks prior to study treatment initiation.
• History of another active malignancy within the past 2 years (with specific exceptions for certain early-stage cancers).

Sponsors & Collaborators

• Zhijie Wang: lead
• Hebei Medical University Fourth Hospital: collaborator
• Peking University Cancer Hospital & Institute: collaborator

Study Sites (1)

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital

Beijing, Beijing Municipality, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

130-nm albumin-bound paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Central Study Contacts

Zhijie Wang, MD

CONTACT

+86 13466323860; jie_969@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 23, 2025
• First Posted: October 1, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)