A Study Evaluating Neoadjuvant Chemotherapy, Concurrent Chemoradiotherapy Combined With Dual Immune Checkpoint Blockade in Patients With Locally Advanced Non-Small Cell Lung Cancer

NCT07103395 | Recruiting Phase 2

• 1 other identifier: GASTO-10135
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This study will enroll patients with locally advanced non-small cell lung cancer (NSCLC). Patients will receive neoadjuvant chemotherapy combined with dual immune checkpoint blockade (PD-1/CTLA-4), bevacizumab and thymosin alpha 1, followed by concurrent chemoradiotherapy, and finally consolidation therapy with dual immune checkpoint blockade (PD-1/CTLA-4), surufatinib and thymosin alpha 1. The study aims to evaluate the efficacy and safety of this treatment regimen.

Conditions

Lung Cancer (NSCLC)

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  PFS measures the time from the start date of treatment to disease progression, death from any cause or last follow up if alive.

  2-year

Secondary Outcomes (3)

• Objective response rate

  2 month after treatment

• Overall survival

  2-year

• Treatment-related toxicity

  through study completion, an average of 18 months

Study Arms (1)

The study group

EXPERIMENTAL

Patients will receive neoadjuvant chemotherapy combined with iparomlimab and tuvonralimab and thymosin alpha 1, followed by concurrent chemoradiotherapy, and finally consolidation therapy with iparomlimab and tuvonralimab and thymosin alpha 1.

Drug: Neoadjuvant therapy; Radiation: Radiotherapy; Drug: Consolidative therapy

Interventions

Radiotherapy RADIATION

Definitive dose of hypofractionated radiotherapy was delivered to patients, with concurrent chemotherapy and surufatinib.

The study group

Consolidative therapy DRUG

Consolidation therapy consists of iparomlimab and tuvonralimab, surufatinib and thymosin alpha 1, for a total duration of 1 year.

The study group

Neoadjuvant therapy DRUG

The neoadjuvant regimen prior to radiotherapy consists of albumin-bound paclitaxel/pemetrexed, cisplatin, Bevacizumab, iparomlimab and tuvonralimab, and thymosin alpha 1.

The study group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females aged 18 to 75 years or older;
• Patients must have histologically or cytologically confirmed locally advanced, unresectable (Stage III) non-small cell lung cancer (NSCLC);
• EGFR, ALK, and ROS1 wild-type;
• No prior chemotherapy, radiotherapy, surgery, targeted therapy, or immunotherapy;
• Expected survival ≥ 12 weeks;
• WHO Performance Status (PS) score of 0 or 1;
• Female subjects must not be breastfeeding;
• Women of childbearing potential (WOCBP) must agree to use contraception during the study treatment and for 5 months after the last dose of study drug (i.e., 30 days \[one ovulation cycle\] plus approximately five half-lives of the study drug);
• Adequate organ and bone marrow function as defined by the following criteria:
• Forced Expiratory Volume in 1 second (FEV1) ≥ 800 mL;
• Absolute neutrophil count ≥ 1.5 × 10⁹/L;
• Platelets ≥ 100 × 10⁹/L;
• Hemoglobin ≥ 9.0 g/dL;
• Creatinine clearance ≥ 50 mL/min as calculated by the Cockcroft-Gault formula (Cockcroft and Gault, 1976);
• Serum bilirubin ≤ 1.5 × upper limit of normal (ULN);

You may not qualify if:

• Concurrent enrolment in another clinical study, unless it is an observational(non-interventional) clinical study;
• Mixed small cell and non-small cell lung cancer histology;
• Prior use of anti-PD-1, anti-PD-L1, or anti-CTLA4 antibodies;
• Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access;
• Active or prior documented autoimmune disease within the past 2 years;
• Active or prior documented inflammatory bowel disease (eg. Crohn's disease, ulcerative colitis);
• History of primary immunodeficiency;
• History of organ transplant that requires therapeutic immunosuppression;
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent;
• Known history of tuberculosis;
• History of another primary malignancy within 5 years prior to starting treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study;
• Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control.
• Patients who develop distant metastasis;
• Patients who develop locoregional disease progression and the irradiation dose of normal tissue will exceed the limit.
• World Health Organization (WHO) Performance Status of 2-4;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510000, China

RECRUITING

Related Publications (6)

• Danielli R, Cisternino F, Giannarelli D, Calabro L, Camerini R, Savelli V, Bova G, Dragonetti R, Di Giacomo AM, Altomonte M, Maio M. Long-term follow up of metastatic melanoma patients treated with Thymosin alpha-1: investigating immune checkpoints synergy. Expert Opin Biol Ther. 2018 Jul;18(sup1):77-83. doi: 10.1080/14712598.2018.1494717.

  PMID: 30063847 BACKGROUND

• Garaci E, Pica F, Rasi G, Favalli C. Thymosin alpha 1 in the treatment of cancer: from basic research to clinical application. Int J Immunopharmacol. 2000 Dec;22(12):1067-76. doi: 10.1016/s0192-0561(00)00075-8.

  PMID: 11137613 BACKGROUND

• Garaci E, Pica F, Serafino A, Balestrieri E, Matteucci C, Moroni G, Sorrentino R, Zonfrillo M, Pierimarchi P, Sinibaldi-Vallebona P. Thymosin alpha1 and cancer: action on immune effector and tumor target cells. Ann N Y Acad Sci. 2012 Oct;1269:26-33. doi: 10.1111/j.1749-6632.2012.06697.x.

  PMID: 23045967 BACKGROUND

• Provencio M, Nadal E, Insa A, Garcia-Campelo MR, Casal-Rubio J, Domine M, Majem M, Rodriguez-Abreu D, Martinez-Marti A, De Castro Carpeno J, Cobo M, Lopez Vivanco G, Del Barco E, Bernabe Caro R, Vinolas N, Barneto Aranda I, Viteri S, Pereira E, Royuela A, Casarrubios M, Salas Anton C, Parra ER, Wistuba I, Calvo V, Laza-Briviesca R, Romero A, Massuti B, Cruz-Bermudez A. Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (NADIM): an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020 Nov;21(11):1413-1422. doi: 10.1016/S1470-2045(20)30453-8. Epub 2020 Sep 24.

  PMID: 32979984 BACKGROUND

• Huang Y, Yang Y, Zhao Y, Zhao H, Zhou N, Zhang Y, Chen L, Zhou T, Chen G, Wu T, Lu L, Xue S, Kang X, Zhang L, Fang W. QL1706 (anti-PD-1 IgG4/CTLA-4 antibody) plus chemotherapy with or without bevacizumab in advanced non-small cell lung cancer: a multi-cohort, phase II study. Signal Transduct Target Ther. 2024 Jan 29;9(1):23. doi: 10.1038/s41392-023-01731-x.

  PMID: 38282003 BACKGROUND

• Cheng W, Kang K, Zhao A, Wu Y. Dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 in lung cancer. J Hematol Oncol. 2024 Jul 27;17(1):54. doi: 10.1186/s13045-024-01581-2.

  PMID: 39068460 BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Neoadjuvant Therapy; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Central Study Contacts

DaQuan Wang, MD.

CONTACT

+862087343031; wangdq@sysucc.org.cn

Study Design

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

Study Record Dates

• First Submitted: July 16, 2025
• First Posted: August 5, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 30, 2029
• Study Completion (Estimated): December 30, 2029
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)