The Impact of Thymosin α-1 on the Efficacy of Concurrent Chemoradiotherapy Followed by Immunotherpay Consolidation for Locally Advanced NSCLC

NCT06139419 | Active Not Recruiting Phase 2

• 1 other identifier: GASTO-1098
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective phase II randomized study is to determine the impact of thymosin alpha-1 on the concurrent chemoradiotherpay followed by immunotherapy consolidation in patients with locally advanced NSCLC by assessing the survival outcomes, treatment responses and toxicities.

Conditions

Non-small Cell Lung Cancer

Keywords

non-small cell lung cancer; Thymosin alpha-1; concurrent chemoradiotherpay; immunotherapy consolidation

Outcome Measures

Primary Outcomes (1)

• Completion rate of immunotherapy

  Proportion of participants completing 12 months of consolidation of immutherapy

  Calculated from the start of treatment to one year after the last treatment completion

Secondary Outcomes (7)

• Overall survival

  2 years

• Progression-free survival

  one year

• Incidence of ≥grade 2 pneumonia

  through study completion, an average of 1 year

• Drop-out rate during the I/O consolidation

  One year

• The absolute count of total lymphocyte in peripheral blood

  Calculated from the start of treatment to one year after the last treatment completion; up to 18 months

Study Arms (2)

Concurrent Tα-1 group

EXPERIMENTAL

In this concurrent Tα-1 group, participants receive concurrent chemoradiotherapy followed by immunotherapy consolidation. During this treatment, thymosin alpha-1 was administered at 4.8mg each time.

Radiation: definitive radiotherapy; Drug: induction chemo-immunotherapy; Drug: concurrent chemotherapy; Drug: Immunotheapy consolidation; Drug: Thymosin Alpha1

Control group

OTHER

In control group, participants receive concurrent chemoradiotherapy followed by immunotherapy consolidation.

Radiation: definitive radiotherapy; Drug: induction chemo-immunotherapy; Drug: concurrent chemotherapy; Drug: Immunotheapy consolidation

Interventions

definitive radiotherapy RADIATION

Participants were treated with definitive thoracic radiotherapy

Concurrent Tα-1 group; Control group

induction chemo-immunotherapy DRUG

All participants receive two cycles of albumin-bound paclitaxel (260mg/m2) on d1 and cisplatin (25mg/m2) from d1 to d3 in combination with tislelizumab (200mg) on d1.

Also known as: albumin-bound paclitaxel, cisplatin, tislelizumab

Concurrent Tα-1 group; Control group

concurrent chemotherapy DRUG

Concurrent chemotherapy consists of weekly albumin-bound paclitaxel (50mg/m2) and cisplatin (25mg/m2).

Also known as: albumin-bound paclitaxel, cisplatin

Concurrent Tα-1 group; Control group

Immunotheapy consolidation DRUG

Participants without disease progression, grade ≥3 toxicities, and/or grade ≥2 pneumonitis after CCRT receive tislelizumab 200 mg (Q3W) for up to 12 months.

Also known as: tislelizumab

Concurrent Tα-1 group; Control group

Thymosin Alpha1 DRUG

Participants in the Tα1 treatment group will receive Tα1 from the beginning of induction chemo-immunotherapy until the completion of immunotherapy consolidation. In detail, Tα-1 would be administered according to the following three stages: 1. Induction chemo-immunotherapy: Tα-1 will be subcutaneously administered at 4.8 mg on d1 and d3 for each cycle. 2. Concurrent chemoradiotherapy: Tα-1 will be subcutaneously administered at 4.8mg biweekly. 3. Immunotherpay consolidation: Tα-1 will be administered concurrently with tislelizumab at 4.8mg (Q3W) for up to 12 months.

Also known as: thymalfasin

Concurrent Tα-1 group

Eligibility Criteria

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

You may qualify if:

• aged ≥18 years old
• histologically confirmed locally advanced and unresectable NSCLC;
• no prior radiotherapy or surgery;
• with the life expectancy over 12 weeks;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• adequate bone marrow and hepatic and renal functions;
• informed consent

You may not qualify if:

• Concurrent enrollment in another clinical trial, unless it is an observational (non-interventional) clinical study;
• With histologically documented combined small-cell lung carcinoma;
• Major surgery (excluding vascular access placement) within 4 weeks prior to enrollment in the study;
• 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 innate immunodeficiency;
• History of organ transplant that requires the use of immunosuppressives;
• A mean heart rate-corrected QT interval (QTc) ≥ 470 ms, calculated using Bazett correction from 3 ECG calculation cycles;
• Poorly managed health conditions that include but are not limited to persistent or active infections, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, arrhythmia, active peptic ulcer disease or gastritis, active hemorrhagic diseases, hepatitis C or human immunodeficiency virus (HIV) infection, hepatitis B (positive HBsAg and HBV DNA \> 500 IU/ml), and mental disorders/social conditions that may hinder the compliance with the study requirements or the ability to give written informed consent willingly;
• Active tuberculosis;
• Receipt of live or attenuated vaccination within 30 days prior to the first dose of the investigational agents;
• History of another primary malignancy within the past 5 years, excluding adequately treated basal or squamous cell skin cancers or cervical carcinoma in situ;
• Pregnant/breastfeeding women or males/females of reproductive potential who do not use contraception.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun yat-sen university cancer center

Guangzhou, Guangdong, 510000, China

Location

Related Publications (9)

• Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, Vansteenkiste JF, Garassino MC, Hui R, Quantin X, Rimner A, Wu YL, Ozguroglu M, Lee KH, Kato T, de Wit M, Kurata T, Reck M, Cho BC, Senan S, Naidoo J, Mann H, Newton M, Thiyagarajah P, Antonia SJ. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022 Apr 20;40(12):1301-1311. doi: 10.1200/JCO.21.01308. Epub 2022 Feb 2.

  PMID: 35108059 BACKGROUND

• Yegya-Raman N, Friedes C, Sun L, Iocolano M, Kim KN, Doucette A, Cohen RB, Robinson KW, Levin WP, Cengel KA, Lally B, Agarwal M, D'Avella CA, Marmarelis ME, Kosteva JA, Singh AP, Ciunci CA, Aggarwal C, Berman AT, Langer CJ, Feigenberg SJ. Utilization and Factors Precluding Receipt of Checkpoint Inhibitor Consolidation for Stage III NSCLC in a Large US Academic Health System. Clin Lung Cancer. 2023 Jul;24(5):474-482. doi: 10.1016/j.cllc.2023.03.013. Epub 2023 Apr 3.

  PMID: 37076396 BACKGROUND

• Bryant AK, Yin H, Schipper MJ, Paximadis PA, Boike TP, Bergsma DP, Movsas B, Dess RT, Mietzel MA, Kendrick R, Seferi M, Dominello MM, Matuszak MM, Jagsi R, Hayman JA, Pierce LJ, Jolly S; Michigan Radiation Oncology Quality Consortium. Uptake of Adjuvant Durvalumab After Definitive Concurrent Chemoradiotherapy for Stage III Nonsmall-cell Lung Cancer. Am J Clin Oncol. 2022 Apr 1;45(4):142-145. doi: 10.1097/COC.0000000000000899.

  PMID: 35271524 BACKGROUND

• Wu J, Zhou L, Liu J, Ma G, Kou Q, He Z, Chen J, Ou-Yang B, Chen M, Li Y, Wu X, Gu B, Chen L, Zou Z, Qiang X, Chen Y, Lin A, Zhang G, Guan X. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care. 2013 Jan 17;17(1):R8. doi: 10.1186/cc11932.

  PMID: 23327199 BACKGROUND

• Romani L, Bistoni F, Gaziano R, Bozza S, Montagnoli C, Perruccio K, Pitzurra L, Bellocchio S, Velardi A, Rasi G, Di Francesco P, Garaci E. Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling. Blood. 2004 Jun 1;103(11):4232-9. doi: 10.1182/blood-2003-11-4036. Epub 2004 Feb 24.

  PMID: 14982877 BACKGROUND

• Liu F, Qiu B, Xi Y, Luo Y, Luo Q, Wu Y, Chen N, Zhou R, Guo J, Wu Q, Xiong M, Liu H. Efficacy of Thymosin alpha1 in Management of Radiation Pneumonitis in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiotherapy: A Phase 2 Clinical Trial (GASTO-1043). Int J Radiat Oncol Biol Phys. 2022 Nov 1;114(3):433-443. doi: 10.1016/j.ijrobp.2022.07.009. Epub 2022 Jul 21.

  PMID: 35870709 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

• Wara WM, Ammann AJ, Wara DW. Effect of thymosin and irradiation on immune modulation in head and neck and esophageal cancer patients. Cancer Treat Rep. 1978 Nov;62(11):1775-8.

  PMID: 728896 BACKGROUND

• 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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Albumin-Bound Paclitaxel; Cisplatin; tislelizumab; Thymalfasin

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)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Thymosin; Thymus Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides

Study Officials

• Hui Liu, Professor

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 30, 2023
• First Posted: November 18, 2023
• Study Start: July 25, 2023
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): August 30, 2026
• Last Updated: November 17, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)