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NCT06139419·Phase 2·INTERVENTIONAL

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

Status

Active, not recruiting

Phase

Phase 2

Enrollment

114

Locations

1

Results

Not posted

Publications

9

Study summary

What the protocol is testing.

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.

Full detailed description

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. Patients with locally advanced NSCLC who will receive concurrent radiochemotherapy followed by immunotherapy consolidation will be randomly divided into two groups (concurrent Tα1 treatment group and control group \[in which Tα1 will not be used\]), and the overall survivals, progression-free survivals (PFS), completion rate of immunotherapy consolidation, toxicities/adverse effects, and peripheral blood immune biomarkers will be compared between these two groups.

Interventions

Treatment arms and agents.

RADIATION

definitive radiotherapy

Participants were treated with definitive thoracic radiotherapy

DRUG

induction chemo-immunotherapy

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.

DRUG

concurrent chemotherapy

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

DRUG

Immunotheapy consolidation

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

DRUG

Thymosin Alpha1

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.

Timeline

From registration to results.

  1. First posted

    Nov 18, 2023

  2. Study start

    Jul 25, 2023

  3. Primary completion

    Aug 30, 2026

  4. Study completion

    Aug 30, 2026

  5. Results posted

    Not reported

  6. Registry updated

    Nov 17, 2025

Outcomes

What the study measures.

Primary outcomes

Completion rate of immunotherapy

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

Proportion of participants completing 12 months of consolidation of immutherapy

Secondary outcomes

Overall survival

Time frame · 2 years

Progression-free survival

Time frame · one year

Incidence of ≥grade 2 pneumonia

Time frame · through study completion, an average of 1 year

Drop-out rate during the I/O consolidation

Time frame · One year

The absolute count of total lymphocyte in peripheral blood

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

Measured at baseline, before immunotherapy, and every 3-4 months thereafter until the end of immunotherapy.

The expression of peripheral blood cytokines (including IL2, IL4, IL6, IL10, TNF-α, and IFN-γ)

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

Measured at baseline, before immunotherapy, and every 3-4 months thereafter until the end of immunotherapy.

The absolute count of peripheral blood lymphocyte subsets (including CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD3-CD16+CD56+, and CD56+ NK cells, PD-1+CD8+ T cells, Tim3+ CD8+ T cells, CD62lowCD4+ T cells, PD-1+CD4+ T cells, and Tim3+CD4+ T cells

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

Measured at baseline, before immunotherapy, and every 3-4 months thereafter until the end of immunotherapy.

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
Not reported
Sex
ALL
Healthy volunteers
No

Inclusion Criteria: * 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 Exclusion Criteria: * 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.

Study locations

1 registered sites.

China. Showing up to 24 locations stored in the fast local snapshot.

Sun yat-sen university cancer center

Guangzhou, Guangdong, China

Publications

Results and literature.

PMID 35108059Spigel 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 37076396Yegya-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 35271524Bryant 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 23327199Wu 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 14982877Romani 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 35870709Liu 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 23045967Garaci 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 728896Wara 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 30063847Danielli 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.

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