Efficacy and Safety of Induction Benmelstobart Plus Anlotinib and Chemotherapy Followed by Concurrent Chemoradiotherapy and Benmelstobart Maintenance Versus Concurrent Chemoradiotherapy Followed by Benmelstobart Maintenance in Patients With Unresectable Stage III NSCLC

NCT07643350 | Not Yet Recruiting Phase 2

• 1 other identifier: R26036
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to compare the efficacy and safety of induction Benmelstobart plus Anlotinib and chemotherapy followed by concurrent chemoradiotherapy (CCRT) and subsequent Benmelstobart maintenance versus CCRT followed by Benmelstobart maintenance in patients with unresectable stage III NSCLC. Additionally, high-throughput sequencing and multi-omics analysis will be performed on patient-derived tissue and blood samples. By integrating baseline characteristics with clinical data, we aim to identify key determinants of treatment efficacy and prognosis, thereby establishing a precision evaluation system for therapeutic outcomes.

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  The duration from initiation of antitumor therapy until the documentation of disease progression (according to RECIST v1.1) or death from any cause (whichever occurs first).Up to 60 months from randomization

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Primary efficacy assessment at Week 6 after randomization for the first 12 months, followed by every 3 months until disease progression, death or withdrawal of consent

• Disease Control Rate (DCR)

  The proportion of subjects who achieved optimal overall response confirmed as CR, PR, or SD (according to the RECIST v1.1 )，Primary efficacy assessment at Week 6 after randomization for the first 12 months, followed by every 3 months

• OS

  Time to death from any cause at the initiation of antitumor therapy, up to 60 months from randomization

Study Arms (2)

Group A:Benmelstobart + Anlotinib+chemotherapy

EXPERIMENTAL

Benmelstobart + Anlotinib + platinum-based dual-drug chemotherapy (2 cycles of induction therapy) → radical concurrent chemoradiotherapy (Benmelstobart and anlotinib discontinued during radiotherapy) → Benmelstobart maintenance therapy (for up to 1 year)

Drug: benmelstobart combined with chemotherapy and anlotinib

Group B：radical concurrent chemoradiotherapy

EXPERIMENTAL

radical concurrent chemoradiotherapy → Maintenance therapy with Benmelstobart (for up to 1 year)

Biological: Benmelstobart

Interventions

Benmelstobart BIOLOGICAL

Group B:radical concurrent chemoradiotherapy → Maintenance therapy with Benmelstobart (for up to 1 year)

Group B：radical concurrent chemoradiotherapy

benmelstobart combined with chemotherapy and anlotinib DRUG

Group A:Benmelstobart + Anlotinib + platinum-based dual-drug chemotherapy (2 cycles of induction therapy) → radical concurrent chemoradiotherapy (Benmelstobart and anlotinib discontinued during radiotherapy) → Benmelstobart maintenance therapy (for up to 1 year)。

Group A:Benmelstobart + Anlotinib+chemotherapy

Eligibility Criteria

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

You may qualify if:

• \. Voluntary signing of a written ICF.
• \. Age at enrollment: 18-75 years; both sexes are eligible.
• \. Eastern Cooperative Oncology Group (ECOG) performance status score: 0 or 1.
• \. Expected survival: ≥3 months.
• \. Histologically or cytologically confirmed stage III NSCLC (classified according to the International Union Against Cancer and the American Joint Committee on Cancer's 9th edition of the lung cancer TNM staging system).
• \. Definitively determined as unresectable after MDT discussion.
• \. The primary driver genes must not harbor sensitive mutations (including EGFR (exon 19 deletion, exon 21 L858R point mutation, exon 20 insertion, etc.), ALK fusion, ROS1 fusion, MET exon 14 skipping mutation, HER2 exon 20 mutation, BRAF V600E mutation, RET fusion, NTRK fusion). For non-squamous NSCLC, a prior tissue-based common genetic testing report must be provided; otherwise, tumor tissue samples (archived or fresh, primary or metastatic) must be collected prior to enrollment for genetic mutation status assessment (at a local laboratory or central laboratory). For squamous NSCLC subjects with a smoking history or current smoking status, if the prior primary driver gene mutation status is unknown, no corresponding testing is required prior to enrollment, and the status shall be considered negative.
• \. No prior systemic antitumor therapy or chest radiotherapy for NSCLC.
• \. At least one measurable lesion according to RECIST v1.1, and such lesions must be suitable for repeated accurate measurement per RECIST v1.1 criteria. -10. Subjects must provide tumor tissue samples diagnosed as locally advanced tumors at the time of diagnosis or thereafter, including archived or freshly obtained uncolored formalin-fixed paraffin-embedded (FFPE) pathological sections (preferably recently obtained tumor tissue samples), approximately 10-25 sections (of which approximately 10-15 sections are required for EGFR and ALK testing, and approximately 10 sections for PD-L1 expression testing; however, additional sections must be provided if the central laboratory determines that the sample is insufficient for testing), or fresh tumor tissue specimens (frozen in liquid nitrogen for omics research). Tumor lesions used for fresh biopsy should not be designated as RECIST v1.1 target lesions unless the lesion is the only measurable lesion. For archived samples, collection must occur after the last systemic treatment, and the collection site must not have undergone radiotherapy. Note: If a subject's archived sample does not meet the above requirements, the investigator may determine that the biopsy does not serve the subject's best interests and may, after discussion with the project team, permit the use of the archived sample.
• Fertile female subjects must have undergone a urine or serum pregnancy test within 7 days prior to the first medication administration (if the urine pregnancy test result is not negative, a serum pregnancy test must be performed, with the serum result serving as the definitive determination), and the result must be negative. If a fertile female subject has sexual intercourse with an unmarried male partner, she must have used an acceptable contraceptive method since the start of screening and must agree to continue using contraception for 120 days after the last administration of the antitumor drug; whether contraception should be discontinued after this period should be discussed with the investigator.
• \. If an unmarried male subject has sexual intercourse with a fertile female partner, he must have used an effective contraceptive method from the start of screening until 120 days after the last administration; whether contraception should be discontinued after this time point should be discussed with the investigator.
• \. The subject must be willing and able to comply with all scheduled visits, treatment regimens, laboratory tests, and other study requirements.

You may not qualify if:

• \. Histopathological presence of any small cell carcinoma components, as well as specific types such as salivary gland type and SMARCA4 deletion.
• \. Except for NSCLC, the subject had suffered from other malignancies within the preceding 5 years. Subjects who have been cured of other tumors through local treatment (e.g., basal or squamous cell carcinoma of the skin, superficial bladder cancer, cervical or breast carcinoma in situ) are not excluded.
• \. Concurrent enrollment in another clinical study, unless it is an observational, non-interventional clinical study or a follow-up phase of an intervention study.
• \. Previous local treatments targeting the tumor lesion, such as thoracic radiotherapy or radiofrequency ablation.
• \. Receiving nonspecific immunomodulatory therapy (e.g., interleukins, interferons, thym peptides, tumor necrosis factor, etc., excluding IL-11 for thrombocytopenia) within 2 weeks prior to the first dose; or receiving herbal or proprietary Chinese medicines with antitumor indications within 1 week prior to the first dose.
• \. Suffering from an active autoimmune disease requiring systemic treatment within the past two years (e.g., treatment with disease-modifying drugs, corticosteroids, or immunosuppressants). Alternative therapies (e.g., thyroxine, insulin, or physiological corticosteroid replacement for adrenal or pituitary insufficiency) are not considered systemic treatments.
• \. History of immunodeficiency; positive HIV antibody test; or current long-term use of systemic corticosteroids or other immunosuppressants.
• \. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• \. Non-infectious pneumonia/interstitial lung disease requiring systemic glucocorticoid therapy within the past 5 years or currently.
• Severe infections occurring within 4 weeks prior to the first dose, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; active infections treated with systemic anti-infective therapy within 2 weeks prior to the first dose (excluding antiviral therapy for hepatitis B or hepatitis C).
• Subjects with active Hepatitis B (Hepatitis B surface antigen \[HBsAg\] positive AND Hepatitis B virus DNA \[HBVDNA\] \>1,000 copies/mL \[200IU/mL\] or above the lower limit of detection); note that HBsAg-positive subjects are required to receive antiviral therapy against Hepatitis B during the study treatment period. Subjects with active Hepatitis C (Hepatitis C virus \[HCV\] antibody positive AND HCV RNA levels above the lower limit of detection).
• Has undergone major surgical procedures or sustained severe trauma within 30 days prior to the first dose administration, or plans to undergo major surgery within 30 days after the first dose (as determined by the investigator); has undergone minor local surgeries within 3 days prior to the first dose administration (excluding peripheral venous catheterization and intravenous infusion port implantation).
• \. The tumor invades or compresses surrounding vital organs (e.g., aorta, heart and pericardium, superior vena cava, trachea, esophagus) or carries a risk of esophageal-tracheal fistula or esophageal-plenic fistula; mediastinal lymph node metastasis involves the trachea or main bronchi with a risk of bronchial fistula.
• \. Currently has uncontrolled comorbid conditions, including but not limited to decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe active peptic ulcer disease or gastritis, or psychiatric/social conditions that may limit the subject's adherence to study requirements or affect their capacity to provide written informed consent.
• \. Has a history of myocarditis, cardiomyopathy, or malignant arrhythmias; experienced unstable angina, myocardial infarction, congestive heart failure, or vascular diseases (e.g., aneurysm with rupture risk) requiring hospitalization within 12 months prior to the first dose; or has other cardiac injuries that may affect the safety evaluation of antineoplastic agents.

Sponsors & Collaborators

• The Third Xiangya Hospital of Central South University: lead

Study Sites (1)

ThirdXiangyaHCSU

Changsha, Hunan, China

Location

Related Publications (4)

• Li Y, Juergens RA, Finley C, Swaminath A. Current and Future Treatment Options in the Management of Stage III NSCLC. J Thorac Oncol. 2023 Nov;18(11):1478-1491. doi: 10.1016/j.jtho.2023.08.011. Epub 2023 Aug 11.

  PMID: 37574133 RESULT

• Ganti AK, Klein AB, Cotarla I, Seal B, Chou E. Update of Incidence, Prevalence, Survival, and Initial Treatment in Patients With Non-Small Cell Lung Cancer in the US. JAMA Oncol. 2021 Dec 1;7(12):1824-1832. doi: 10.1001/jamaoncol.2021.4932.

  PMID: 34673888 RESULT

• Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4.

  PMID: 38572751 RESULT

• Xia C, Dong X, Li H, Cao M, Sun D, He S, Yang F, Yan X, Zhang S, Li N, Chen W. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl). 2022 Feb 9;135(5):584-590. doi: 10.1097/CM9.0000000000002108.

  PMID: 35143424 RESULT

MeSH Terms

Interventions

Drug Therapy; anlotinib

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Xuewen Liu

CONTACT

+8618711033808; aveinliu@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2026
• First Posted: June 11, 2026
• Study Start: May 15, 2026
• Primary Completion (Estimated): May 15, 2029
• Study Completion (Estimated): May 15, 2031
• Last Updated: June 11, 2026

Record last verified: 2026-05

Locations

CN (1)