Neoadjuvant immunochemotherapy plus thymalfasin in locally advanced gastric cancer: a prospective clinical trial.

Xu H, Li F, Li B, Yang D, Liu T, Xia Y, Hua H, Li Q, Wang J, Liu H, Xu Z

BMC medicine26 Feb 2026

PMID41749205PMCIDPMC12964648DOI10.1186/s12916-026-04740-zPepBankPUB-41749205

Summary

BackgroundNeoadjuvant immunochemotherapy has emerged as a promising strategy for locally advanced gastric and gastroesophageal junction (G/EGJ) adenocarcinoma, but a substantial proportion of patients derive limited benefit. Thymalfasin is an immunomodulatory peptide that may amplify antitumor immunity while attenuating toxicity. We conducted a phase II trial to evaluate anti-PD-1 plus SOX (S-1 and oxaliplatin) immunochemotherapy combined with thymalfasin as neoadjuvant treatment for G/EGJ adenocarcinoma.MethodsThe prospective trial enrolled patients aged 18-75 with cStage III G/EGJ adenocarcinoma, ECOG 0-1, and adequate organ function. Treatment included three 21-day cycles of serplulimab (anti-PD-1) plus SOX (S-1 and oxaliplatin) and 9 weeks of thymalfasin, followed by curative gastrectomy. The primary endpoint was pathological complete response (pCR). Secondary endpoints included major pathological response (MPR), safety, survival, and other efficacy measures. Peripheral immune remodeling was assessed by flow cytometry, and bulk RNA sequencing of peripheral blood mononuclear cells (PBMCs) interrogated thymalfasin-associated transcriptional programs.ResultsThirty patients were enrolled and all underwent curative-intent minimally invasive gastrectomy. pCR was achieved in 30.0% (9/30), and MPR in 56.7% (17/30). ypN0 status was observed in 63.3% (19/30), with N-stage downstaging in 80.0% (24/30). At a median follow-up of 14.0 months (range 10.0-17.2), only one retroperitoneal nodal relapse had occurred at 14.4 months after diagnosis; no deaths were documented. Any-grade adverse events (AEs) occurred in 93.3% of patients, grade ≥ 3 AEs in 26.7%, and immune-related AEs in 23.3%. Flow cytometry showed expansion of CD8⁺ T cells with increased CD69 expression and a concurrent reduction in HLA-DR-positive T cells, suggesting dynamic remodeling from broad systemic activation toward a more focused effector or memory response. RNA-seq revealed thymalfasin-associated upregulation of genes involved in antigen processing and presentation, type I interferon signaling, and identified immune co-expression modules linked to treatment and response.ConclusionsNeoadjuvant serplulimab, SOX, and thymalfasin produced encouraging pathological response, substantial nodal clearance, and an acceptable safety profile in stage III G/EGJ adenocarcinoma. Peripheral immune and transcriptomic profiling are consistent with a hypothesis in which thymalfasin may help preserve and coordinate systemic antitumor immunity without excessive toxicity. These findings warrant further larger randomized trials.Trial registrationClinicalTrials.gov, NCT06461910, 2024-06-14.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study11

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone11

In this study, Thymosin alpha-1 was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Thymosin alpha-1.

01HumanNot a test of Thymosin alpha-1 aloneNon-randomized trialEfficacy outcome
In stage III gastric or gastroesophageal junction adenocarcinoma, neoadjuvant serplulimab, SOX and thymalfasin gave a pathological complete response in 30.0% (9/30).
In plain wordsIn people with stage III gastric cancer, a before-surgery regimen with thymalfasin and other drugs led to no remaining cancer in 30.0%.
Peptide
Thymosin alpha-1
Outcome
Not applicablePathological complete response
Study
n = 30
Analysis
Primary
Outcome group
Tumor growth · Cancer
Measurements
pCR
30%
9/30 patients
Source sentences
Summary
pCR was achieved in 30.0% (9/30), and MPR in 56.7% (17/30).
2 context sentences(design, population, supporting numbers)
Summary · context
The prospective trial enrolled patients aged 18-75 with cStage III G/EGJ adenocarcinoma, ECOG 0-1, and adequate organ function.
Summary · context
Treatment included three 21-day cycles of serplulimab (anti-PD-1) plus SOX (S-1 and oxaliplatin) and 9 weeks of thymalfasin, followed by curative gastrectomy.
In this study, Thymosin alpha-1 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin alpha-1.
Show in the study text Report a problemFND-4174920501
02HumanNot a test of Thymosin alpha-1 aloneNon-randomized trialEfficacy outcome
In stage III gastric or gastroesophageal junction adenocarcinoma, the regimen with thymalfasin gave a major pathological response in 56.7% (17/30).
In plain wordsIn people with stage III gastric cancer, a before-surgery regimen with thymalfasin and other drugs gave a major pathological response in 56.7%.
Peptide
Thymosin alpha-1
Outcome
Not applicableMajor pathological response
Study
n = 30
Analysis
Secondary
Outcome group
Tumor growth · Cancer
Measurements
MPR
56.7%
17/30 patients
Source sentences
Summary
pCR was achieved in 30.0% (9/30), and MPR in 56.7% (17/30).
2 context sentences(design, population, supporting numbers)
Summary · context
The prospective trial enrolled patients aged 18-75 with cStage III G/EGJ adenocarcinoma, ECOG 0-1, and adequate organ function.
Summary · context
Treatment included three 21-day cycles of serplulimab (anti-PD-1) plus SOX (S-1 and oxaliplatin) and 9 weeks of thymalfasin, followed by curative gastrectomy.
In this study, Thymosin alpha-1 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin alpha-1.
Show in the study text Report a problemFND-4174920502
03HumanNot a test of Thymosin alpha-1 aloneNon-randomized trialEfficacy outcome
In stage III gastric or gastroesophageal junction adenocarcinoma, the regimen with thymalfasin led to ypN0 status in 63.3% (19/30).
In plain wordsIn people with stage III gastric cancer, a regimen with thymalfasin and other drugs left no cancer in the lymph nodes in 63.3%.
Peptide
Thymosin alpha-1
Outcome
Not applicableypN0 status
Study
n = 30
Outcome group
Tumor growth · Cancer
Measurements
ypN0
63.3%
19/30 patients
Source sentences
Summary
ypN0 status was observed in 63.3% (19/30), with N-stage downstaging in 80.0% (24/30).
2 context sentences(design, population, supporting numbers)
Summary · context
The prospective trial enrolled patients aged 18-75 with cStage III G/EGJ adenocarcinoma, ECOG 0-1, and adequate organ function.
Summary · context
Treatment included three 21-day cycles of serplulimab (anti-PD-1) plus SOX (S-1 and oxaliplatin) and 9 weeks of thymalfasin, followed by curative gastrectomy.
In this study, Thymosin alpha-1 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin alpha-1.
Show in the study text Report a problemFND-4174920503
04HumanNot a test of Thymosin alpha-1 aloneNon-randomized trialEfficacy outcome
In stage III gastric or gastroesophageal junction adenocarcinoma, the regimen with thymalfasin led to N-stage downstaging in 80.0% (24/30).
In plain wordsIn people with stage III gastric cancer, a regimen with thymalfasin and other drugs lowered the lymph node stage in 80.0%.
Peptide
Thymosin alpha-1
Outcome
Not applicableN-stage downstaging
Study
n = 30
Outcome group
Tumor growth · Cancer
Measurements
N-stage downstaging
80%
24/30 patients
Source sentences
Summary
ypN0 status was observed in 63.3% (19/30), with N-stage downstaging in 80.0% (24/30).
2 context sentences(design, population, supporting numbers)
Summary · context
The prospective trial enrolled patients aged 18-75 with cStage III G/EGJ adenocarcinoma, ECOG 0-1, and adequate organ function.
Summary · context
Treatment included three 21-day cycles of serplulimab (anti-PD-1) plus SOX (S-1 and oxaliplatin) and 9 weeks of thymalfasin, followed by curative gastrectomy.
In this study, Thymosin alpha-1 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin alpha-1.
Show in the study text Report a problemFND-4174920504
05HumanNot a test of Thymosin alpha-1 aloneNon-randomized trialEfficacy outcome
At a median follow-up of 14.0 months, one retroperitoneal nodal relapse had occurred and no deaths were documented after the regimen with thymalfasin.
In plain wordsAt a median of 14.0 months, one person had a relapse and nobody had died after a regimen that included thymalfasin.
Peptide
Thymosin alpha-1
Outcome
Not applicableRelapse and deaths at median 14.0 months follow-up
Study
n = 30
Outcome group
Mortality · Cancer
Source sentences
Summary
At a median follow-up of 14.0 months (range 10.0-17.2), only one retroperitoneal nodal relapse had occurred at 14.4 months after diagnosis; no deaths were documented.
2 context sentences(design, population, supporting numbers)
Summary · context
The prospective trial enrolled patients aged 18-75 with cStage III G/EGJ adenocarcinoma, ECOG 0-1, and adequate organ function.
Summary · context
Treatment included three 21-day cycles of serplulimab (anti-PD-1) plus SOX (S-1 and oxaliplatin) and 9 weeks of thymalfasin, followed by curative gastrectomy.
In this study, Thymosin alpha-1 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin alpha-1.
Show in the study text Report a problemFND-4174920505
06HumanNot a test of Thymosin alpha-1 aloneNon-randomized trialSafety outcome
In patients given serplulimab, SOX and thymalfasin, any-grade adverse events occurred in 93.3%.
In plain wordsIn people given a regimen with thymalfasin and other drugs, 93.3% had at least one side effect.
Peptide
Thymosin alpha-1
Outcome
Not applicableAny-grade adverse events
Study
n = 30
Outcome group
Adverse events · Whole body
Measurements
Any-grade AEs
93.3%
patients
Source sentences
Summary
Any-grade adverse events (AEs) occurred in 93.3% of patients
2 context sentences(design, population, supporting numbers)
Summary · context
The prospective trial enrolled patients aged 18-75 with cStage III G/EGJ adenocarcinoma, ECOG 0-1, and adequate organ function.
Summary · context
Treatment included three 21-day cycles of serplulimab (anti-PD-1) plus SOX (S-1 and oxaliplatin) and 9 weeks of thymalfasin, followed by curative gastrectomy.
In this study, Thymosin alpha-1 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin alpha-1.
Show in the study text Report a problemFND-4174920506
07HumanNot a test of Thymosin alpha-1 aloneNon-randomized trialSafety outcome
In patients given serplulimab, SOX and thymalfasin, grade 3 or higher adverse events occurred in 26.7%.
In plain wordsIn people given a regimen with thymalfasin and other drugs, 26.7% had a severe side effect.
Peptide
Thymosin alpha-1
Outcome
Not applicableGrade 3 or higher adverse events
Study
n = 30
Outcome group
Adverse events · Whole body
Measurements
Grade >=3 AEs
26.7%
patients
Source sentences
Summary
grade ≥ 3 AEs in 26.7%, and immune-related AEs in 23.3%.
2 context sentences(design, population, supporting numbers)
Summary · context
The prospective trial enrolled patients aged 18-75 with cStage III G/EGJ adenocarcinoma, ECOG 0-1, and adequate organ function.
Summary · context
Treatment included three 21-day cycles of serplulimab (anti-PD-1) plus SOX (S-1 and oxaliplatin) and 9 weeks of thymalfasin, followed by curative gastrectomy.
In this study, Thymosin alpha-1 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin alpha-1.
Show in the study text Report a problemFND-4174920507
08HumanNot a test of Thymosin alpha-1 aloneNon-randomized trialSafety outcome
In patients given serplulimab, SOX and thymalfasin, immune-related adverse events occurred in 23.3%.
In plain wordsIn people given a regimen with thymalfasin and other drugs, 23.3% had immune-related side effects.
Peptide
Thymosin alpha-1
Outcome
Not applicableImmune-related adverse events
Study
n = 30
Outcome group
Adverse events · Immune and inflammation
Measurements
Immune-related AEs
23.3%
patients
Source sentences
Summary
and immune-related AEs in 23.3%.
2 context sentences(design, population, supporting numbers)
Summary · context
The prospective trial enrolled patients aged 18-75 with cStage III G/EGJ adenocarcinoma, ECOG 0-1, and adequate organ function.
Summary · context
Treatment included three 21-day cycles of serplulimab (anti-PD-1) plus SOX (S-1 and oxaliplatin) and 9 weeks of thymalfasin, followed by curative gastrectomy.
In this study, Thymosin alpha-1 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin alpha-1.
Show in the study text Report a problemFND-4174920508
09HumanNot a test of Thymosin alpha-1 aloneNon-randomized trialMechanism
In patients with gastric cancer, the regimen with thymalfasin was followed by expansion of CD8+ T cells with increased CD69 expression.
In plain wordsIn people with gastric cancer, a regimen with thymalfasin and other drugs was followed by more CD8+ T cells with higher CD69.
Peptide
Thymosin alpha-1
Outcome
IncreaseCD8+ T cell expansion and CD69 expression
Study
n: not reported in source
Outcome group
Immune response · Immune and inflammation
Source sentences
Summary
Flow cytometry showed expansion of CD8⁺ T cells with increased CD69 expression and a concurrent reduction in HLA-DR-positive T cells, suggesting dynamic remodeling from broad systemic activation toward a more focused effector or memory response.
2 context sentences(design, population, supporting numbers)
Summary · context
The prospective trial enrolled patients aged 18-75 with cStage III G/EGJ adenocarcinoma, ECOG 0-1, and adequate organ function.
Summary · context
Treatment included three 21-day cycles of serplulimab (anti-PD-1) plus SOX (S-1 and oxaliplatin) and 9 weeks of thymalfasin, followed by curative gastrectomy.
In this study, Thymosin alpha-1 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin alpha-1.
Show in the study text Report a problemFND-4174920509
10HumanNot a test of Thymosin alpha-1 aloneNon-randomized trialMechanism
In patients with gastric cancer, the regimen with thymalfasin was followed by a reduction in HLA-DR-positive T cells.
In plain wordsIn people with gastric cancer, a regimen with thymalfasin and other drugs was followed by fewer HLA-DR-positive T cells.
Peptide
Thymosin alpha-1
Outcome
DecreaseHLA-DR-positive T cells
Study
n: not reported in source
Outcome group
Immune response · Immune and inflammation
Source sentences
Summary
Flow cytometry showed expansion of CD8⁺ T cells with increased CD69 expression and a concurrent reduction in HLA-DR-positive T cells, suggesting dynamic remodeling from broad systemic activation toward a more focused effector or memory response.
2 context sentences(design, population, supporting numbers)
Summary · context
The prospective trial enrolled patients aged 18-75 with cStage III G/EGJ adenocarcinoma, ECOG 0-1, and adequate organ function.
Summary · context
Treatment included three 21-day cycles of serplulimab (anti-PD-1) plus SOX (S-1 and oxaliplatin) and 9 weeks of thymalfasin, followed by curative gastrectomy.
In this study, Thymosin alpha-1 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin alpha-1.
Show in the study text Report a problemFND-4174920510
11HumanNot a test of Thymosin alpha-1 aloneNon-randomized trialMechanism
In blood cells from patients given the regimen with thymalfasin, genes for antigen processing and presentation and type I interferon signaling were upregulated.
In plain wordsIn blood cells from people given a regimen with thymalfasin and other drugs, immune genes for antigen handling and interferon signaling were more active.
Peptide
Thymosin alpha-1
Outcome
IncreaseAntigen processing and type I interferon gene expression
Study
n: not reported in source
Outcome group
Immune response · Immune and inflammation
Source sentences
Summary
RNA-seq revealed thymalfasin-associated upregulation of genes involved in antigen processing and presentation, type I interferon signaling, and identified immune co-expression modules linked to treatment and response.
2 context sentences(design, population, supporting numbers)
Summary · context
The prospective trial enrolled patients aged 18-75 with cStage III G/EGJ adenocarcinoma, ECOG 0-1, and adequate organ function.
Summary · context
Treatment included three 21-day cycles of serplulimab (anti-PD-1) plus SOX (S-1 and oxaliplatin) and 9 weeks of thymalfasin, followed by curative gastrectomy.
In this study, Thymosin alpha-1 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin alpha-1.
Show in the study text Report a problemFND-4174920511

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 ongoing · source ClinicalTrials.gov (opens in a new tab)

RecruitingPhase 2NCT06461910

Efficacy and Safety of Anti-PD-1, Thymalfasin, and SOX in Neoadjuvant Treatment of cStage III Gastric/Gastroesophageal Junction Adenocarcinoma

Zekuan Xun = 3014 Jun 2024 to est. Dec 2027

Gastric Cancer · Esophagogastric Junction Adenocarcinoma

Trial page ClinicalTrials.govUpdated 3 Mar 2026

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 3Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 2
9 Oct 2026, 03:03 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:02 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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