Iparomlimab and Tuvonralimab Plus Chemotherapy Before Surgery for Stage III Lung Cancer

NCT07538193 | Not Yet Recruiting

• 1 other identifier: K202511-27
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Background: For patients with resectable stage III-N2b non-small cell lung cancer (NSCLC), optimal perioperative treatment strategies remain an area of active investigation. Iparomlimab and tuvonralimab (QL1706) is a novel bifunctional antibody combination targeting PD-1 and CTLA-4, designed to enhance anti-tumor immunity. Objective: This phase II, single-arm, multicenter study aims to evaluate the efficacy and safety of neoadjuvant iparomlimab and tuvonralimab (QL1706) in combination with platinum-based chemotherapy in patients with resectable stage III-N2b NSCLC. Study Design and Methods: A total of 28 patients will be enrolled across approximately 4 centers in China. Eligible patients (aged ≥18 years, ECOG PS 0-1) with histologically or cytologically confirmed, resectable stage III-N2b NSCLC (AJCC 9th edition) will receive three cycles of neoadjuvant therapy every three weeks. Patients with non-squamous carcinoma will receive iparomlimab and tuvonralimab (5 mg/kg) plus pemetrexed (500 mg/m²) and carboplatin (AUC 5). Patients with squamous carcinoma will receive iparomlimab and tuvonralimab (5 mg/kg) plus nab-paclitaxel (260 mg/m²) and carboplatin (AUC 5). Surgical resection will be performed within 6 weeks following completion of neoadjuvant therapy. Subsequent adjuvant treatment is at the discretion of the investigator. Key Eligibility Criteria: Key inclusion criteria include pathologically confirmed T\<sub\>any\</sub\>N2b disease with mediastinal nodal status confirmed by EBUS/EUS or mediastinoscopy, and the determination by multidisciplinary team (MDT) assessment that the tumor is completely resectable (R0). Key exclusion criteria include known EGFR or ALK positive mutations, prior anti-cancer therapy for current lung cancer, active autoimmune disease, or uncontrolled hepatitis B or C. Study Endpoints: The primary endpoint is the pathological complete response (pCR) rate. Secondary endpoints include major pathological response (MPR) rate, objective response rate (ORR), R0 resection rate, event-free survival (EFS), overall survival (OS), impact on surgical outcomes, and safety. Exploratory endpoints involve biomarker analysis including ctDNA. Sample Size Rationale: Assuming a null hypothesis pCR rate (P0) of 8.8% (based on historical data) and an expected pCR rate (P1) of 28%, with a two-sided α of 5% and 80% power, 24 patients are required. Factoring in a 15% inoperable rate, the total sample size is 28 patients. Statistical Analysis: The primary endpoint, pCR rate, and other binary endpoints will be summarized with frequencies, percentages, and their 95% confidence intervals calculated using the Clopper-Pearson method. Time-to-event endpoints (EFS, OS) will be analyzed using the Kaplan-Meier method. Safety data will be summarized descriptively. Clinical Trial Information: This study is sponsored by The Second Affiliated Hospital of Air Force Medical University, PLA. The Principal Investigator is Dr. Yan Xiaolong.

Conditions

Carcinoma, Non-Small-Cell Lung (NSCLC); Neoplasm Staging; Lymphatic Metastasis

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR) rate

  The percentage of subjects with no residual viable tumor cells in the resected primary tumor bed and lymph nodes after lung cancer resection.

  At the time of surgery, approximately 9-15 weeks after enrollment

Secondary Outcomes (11)

• Major Pathological Response (MPR) rate

  At the time of surgery, approximately 9-15 weeks after enrollment

• Objective Response Rate (ORR)

  From enrollment to pre-surgery assessment, approximately 9-15 weeks

• R0 Resection Rate

  At the time of surgery

• Event-Free Survival (EFS)

  From enrollment to up to 2 years post-surgery

• Overall Survival (OS)

  From enrollment to up to 2 years post-surgery or death

Study Arms (1)

Iparomlimab and Tuvonralimab plus Chemotherapy

EXPERIMENTAL

Iparomlimab and Tuvonralimab combined with Platinum-Based Chemotherapy (Pemetrexed/Carboplatin for Non-squamous; Nab-paclitaxel/Carboplatin for Squamous)

Drug: Iparomlimab and Tuvonralimab combined with Platinum-Based Chemotherapy (Pemetrexed/Carboplatin for Non-squamous; Nab-paclitaxel/Carboplatin for Squamous)

Interventions

Iparomlimab and Tuvonralimab combined with Platinum-Based Chemotherapy (Pemetrexed/Carboplatin for Non-squamous; Nab-paclitaxel/Carboplatin for Squamous) DRUG

Participants receive neoadjuvant treatment with Iparomlimab and Tuvonralimab in combination with platinum-based chemotherapy for three cycles prior to surgical resection. Dosing Regimen: For Non-squamous Carcinoma: Iparomlimab and Tuvonralimab: 5 mg/kg, intravenous infusion, Day 1 Pemetrexed: 500 mg/m², intravenous infusion, Day 1 Carboplatin: AUC 5, intravenous infusion, Day 1 Cycle length: 21 days (every 3 weeks) Total treatment: 3 cycles For Squamous Carcinoma: Iparomlimab and Tuvonralimab: 5 mg/kg, intravenous infusion, Day 1 Nab-paclitaxel: 260 mg/m², intravenous infusion, Day 1 Carboplatin: AUC 5, intravenous infusion, Day 1 Cycle length: 21 days (every 3 weeks) Total treatment: 3 cycles After completion of neoadjuvant therapy, participants undergo surgical resection within 6 weeks. Adjuvant treatment following surgery is administered at the discretion of the investigator and is not specified by this protocol.

Iparomlimab and Tuvonralimab plus Chemotherapy

Eligibility Criteria

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

You may qualify if:

• Voluntarily join the study and sign the Informed Consent Form (ICF).
• ≥18 years old, male or female.
• Histologically or cytologically confirmed T\<sub\>any\</sub\>N2b stage NSCLC (American Joint Committee on Cancer \[AJCC\] 9th edition). Lymph node status must be confirmed by endobronchial ultrasound (EBUS/EUS) or mediastinoscopy for mediastinal lymph nodes. For left-sided stations 5/6 lymph nodes, parasternal mediastinoscopy is recommended to confirm lymph node status; if mediastinoscopy is not performed, station 5/6 lymph node status is diagnosed based on imaging diagnostic criteria.
• Based on MDT assessment (which must include a thoracic surgeon specialized in oncology), the primary NSCLC is deemed to be completely resectable (R0).
• At least one measurable lesion as assessed by the investigator per RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
• Adequate organ function meeting the following requirements (no use of any blood components, cell growth factors, etc., within 14 days before the first dose):
• Absolute neutrophil count ≥1.5×10⁹/L;
• Platelet count ≥100×10⁹/L;
• Hemoglobin ≥90 g/L;
• Serum creatinine ≤1.5×upper limit of normal (ULN) or creatinine clearance (CLcr) ≥40 mL/min calculated by the Cockcroft-Gault formula;
• Total bilirubin ≤1.5×ULN (patients with Gilbert's syndrome may have ≤3×ULN);
• AST and ALT ≤3×ULN;
• International normalized ratio (INR) or activated partial thromboplastin time (APTT) ≤1.5×ULN, unless the subject is receiving anticoagulant therapy;
• Left ventricular ejection fraction (LVEF) ≥50%.

You may not qualify if:

• Known presence of EGFR or ALK positive mutations.
• History of or concurrent other malignancy within the past 5 years (excluding adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical surgery, ductal carcinoma in situ after radical surgery).
• Prior receipt of any anti-tumor therapy for the current lung cancer (e.g., radiotherapy, chemotherapy, targeted therapy, ablation, or other systemic or local anti-tumor therapies).
• Current use of immunosuppressants or systemic hormone therapy for immunosuppressive purposes (dose \>10 mg/day prednisone or equivalent) and continued use within 2 weeks before enrollment (Note: Inhaled or topical corticosteroids and adrenal replacement steroids are permitted in the absence of active autoimmune disease).
• Any active autoimmune disease or history of autoimmune disease, including but not limited to: autoimmune hepatitis, interstitial pneumonia, pulmonary fibrosis, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism.
• Subjects with hypothyroidism controlled by hormone replacement therapy alone are eligible;
• Subjects with skin diseases not requiring systemic treatment such as vitiligo, psoriasis, alopecia, type 1 diabetes, or childhood asthma that has completely resolved and requires no intervention in adulthood are eligible;
• Patients with asthma requiring medical intervention with steroids are not eligible.
• History of allogeneic hematopoietic stem cell transplantation or organ transplantation (except corneal transplantation).
• Congenital or acquired immunodeficiency (e.g., HIV-infected individuals).
• Uncontrolled active hepatitis B (defined as positive hepatitis B surface antigen \[HBsAg\] test at screening with concurrent HBV-DNA test value above the upper limit of normal of the research center's laboratory; subjects with HBV-DNA \<500 IU/mL measured within 28 days before study drug administration and who have received standard local antiviral therapy for at least 4 weeks and are willing to continue antiviral therapy during the study may be enrolled). Subjects with active hepatitis C (defined as positive hepatitis C virus antibody \[HCsAb\] test at screening and positive HCV-RNA).
• History of severe allergic reactions to other monoclonal antibodies.
• Vaccination with live vaccine within 30 days before the first dose of study treatment (continuing until 90 days after the last dose of study treatment). Note: Live vaccines include but are not limited to measles, mumps, rubella, varicella/zoster (chickenpox), yellow fever, rabies, BCG, and typhoid vaccines. Inactivated seasonal influenza vaccines, inactivated COVID-19 vaccines, etc., are permitted.
• Clinically significant cardiovascular or cerebrovascular diseases, including but not limited to:
• Myocardial infarction or unstable angina pectoris within 6 months before the first dose;

Sponsors & Collaborators

• Tang-Du Hospital: lead

Study Sites (1)

Tangdu Hospitial

Xi'an, Shannxi, China

Location

Related Publications (6)

• Provencio M, Nadal E, Gonzalez-Larriba JL, Martinez-Marti A, Bernabe R, Bosch-Barrera J, Casal-Rubio J, Calvo V, Insa A, Ponce S, Reguart N, de Castro J, Mosquera J, Cobo M, Aguilar A, Lopez Vivanco G, Camps C, Lopez-Castro R, Moran T, Barneto I, Rodriguez-Abreu D, Serna-Blasco R, Benitez R, Aguado de la Rosa C, Palmero R, Hernando-Trancho F, Martin-Lopez J, Cruz-Bermudez A, Massuti B, Romero A. Perioperative Nivolumab and Chemotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Aug 10;389(6):504-513. doi: 10.1056/NEJMoa2215530. Epub 2023 Jun 28.

  PMID: 37379158 BACKGROUND

• Cascone T, Awad MM, Spicer JD, He J, Lu S, Sepesi B, Tanaka F, Taube JM, Cornelissen R, Havel L, Karaseva N, Kuzdzal J, Petruzelka LB, Wu L, Pujol JL, Ito H, Ciuleanu TE, de Oliveira Muniz Koch L, Janssens A, Alexandru A, Bohnet S, Moiseyenko FV, Gao Y, Watanabe Y, Coronado Erdmann C, Sathyanarayana P, Meadows-Shropshire S, Blum SI, Provencio Pulla M; CheckMate 77T Investigators. Perioperative Nivolumab in Resectable Lung Cancer. N Engl J Med. 2024 May 16;390(19):1756-1769. doi: 10.1056/NEJMoa2311926.

  PMID: 38749033 BACKGROUND

• Provencio M, Awad MM, Spicer JD, Janssens A, Moiseyenko F, Gao Y, Watanabe Y, Alexandru A, Guisier F, Frost N, Franke F, Hiltermann TJN, He J, Tanaka F, Lu S, Coronado Erdmann C, Sathyanarayana P, Tran P, Devas V, Cascone T. Clinical outcomes with perioperative nivolumab by nodal status in patients with stage III resectable NSCLC: phase 3 CheckMate 77T exploratory analysis. Nat Cancer. 2026 Jan;7(1):169-181. doi: 10.1038/s43018-025-01104-z. Epub 2026 Jan 8.

  PMID: 41507539 BACKGROUND

• Zhao Y, Wang W, Liang H, Yang CJ, D'Amico T, Ng CSH, Liu CC, Petersen RH, Rocco G, Brunelli A, Liu J, He J, Huang W, Liang W, He J; AME Thoracic Surgery Collaborative Group. The Optimal Treatment for Stage IIIA-N2 Non-Small Cell Lung Cancer: A Network Meta-Analysis. Ann Thorac Surg. 2019 Jun;107(6):1866-1875. doi: 10.1016/j.athoracsur.2018.11.024. Epub 2018 Dec 14.

  PMID: 30557543 BACKGROUND

• Carter L, Apte V, Shukla A, Ghose A, Mamidi R, Petohazi A, Makker S, Banerjee S, Boussios S, Banna GL. Stage 3 N2 Lung Cancer: A Multidisciplinary Therapeutic Conundrum. Curr Oncol Rep. 2024 Jan;26(1):65-79. doi: 10.1007/s11912-023-01486-2. Epub 2024 Jan 2.

  PMID: 38180692 BACKGROUND

• Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R, Li L, Wei W, He J. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024 Feb 2;4(1):47-53. doi: 10.1016/j.jncc.2024.01.006. eCollection 2024 Mar.

  PMID: 39036382 BACKGROUND

MeSH Terms

Conditions

Carcinoma; Carcinoma, Non-Small-Cell Lung; Lymphatic Metastasis

Interventions

Platinum Compounds; Pemetrexed; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Inorganic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals

Central Study Contacts

XiaoLong Yan, Doctor of Medicine(M.D.)

CONTACT

+8615991269383; yanxiaolong@fmmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2026
• First Posted: April 20, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)