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Induction Chemoimmunotherapy in Combination With Chemoradiotherapy and Consolidation Immunotherapy in Unresectable Locally Advanced Non-Small Cell Lung Cancer

3. juni 2026 opdateret af: Wen Yu, Shanghai Chest Hospital

A Phase I/II Multicenter Study Evaluating the Safety and Efficacy of Induction Chemoimmunotherapy Followed by Concurrent Chemoradiotherapy and Consolidation Immunotherapy in Unresectable Locally Advanced Non-Small Cell Lung Cancer

STRATUS-NSCLC-01 is a multicenter, phase I/II clinical study designed to evaluate the safety and efficacy of induction chemoimmunotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy in patients with unresectable locally advanced non-small cell lung cancer (NSCLC). Patients are stratified according to baseline tumor extent and radiotherapy feasibility. Participants suitable for definitive thoracic radiotherapy receive induction chemoimmunotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy, while patients with excessive tumor burden or unfavorable dosimetric parameters may receive induction chemoimmunotherapy followed by carbon-ion radiotherapy and consolidation immunotherapy. The study aims to investigate whether treatment intensification before radiotherapy can improve long-term outcomes beyond the standard PACIFIC strategy while maintaining acceptable safety.

Studieoversigt

Detaljeret beskrivelse

Concurrent chemoradiotherapy followed by consolidation immunotherapy has become the standard treatment approach for unresectable locally advanced NSCLC based on the PACIFIC study. However, disease recurrence remains common, and long-term progression-free survival remains unsatisfactory. Strategies to further improve outcomes and optimize integration between systemic therapy and radiotherapy are still needed.

Induction chemoimmunotherapy has demonstrated significant tumor regression and downstaging effects in locally advanced NSCLC. Tumor burden reduction achieved during induction treatment may improve radiotherapy feasibility, enhance target conformity, reduce radiation exposure to surrounding normal tissues, and potentially improve the therapeutic effectiveness of subsequent radiotherapy.

This phase I/II clinical study evaluates tumor-extent stratified multimodality treatment strategies for patients with unresectable locally advanced NSCLC. Patients who are suitable for definitive thoracic radiotherapy receive induction chemoimmunotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy. Patients with excessive tumor burden or unfavorable dosimetric parameters for conventional radiotherapy may receive induction chemoimmunotherapy followed by carbon-ion radiotherapy and consolidation immunotherapy.

The phase I portion consists of a safety lead-in cohort to evaluate treatment tolerability. If predefined safety criteria are met, the study proceeds to phase II efficacy evaluation.

The primary endpoints include treatment safety and progression-free survival (PFS). Secondary endpoints include overall survival (OS), objective response rate (ORR), treatment completion, and treatment-related adverse events. Exploratory analyses include evaluation of minimal residual disease (MRD) and radiomics biomarkers as predictors of response and long-term clinical outcomes.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

30

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

    • Xuhui
      • Shanghai, Xuhui, Kina, 200052
        • Shanghai Chest Hospital

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Beskrivelse

Inclusion Criteria:

  1. Age >18 years, male or female, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  2. Histologically or cytologically confirmed non-small cell lung cancer (NSCLC).
  3. Unresectable stage III NSCLC (according to the 8th edition of the AJCC staging system).
  4. No prior exposure to any other anti-tumor therapy.
  5. Absence of severe medical comorbidities or major organ dysfunction, as assessed by hematology, hepatic, renal, cardiac, and pulmonary function tests, meeting the following criteria: Hematology: Hemoglobin (HB) ≥ 90 g/L (without blood transfusion within 14 days prior to enrollment); absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelet count (PLT) ≥ 100 × 10⁹/L. Biochemistry: Total bilirubin (TBIL) ≤ 1.5 × the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; serum creatinine (Cr) ≤ 1 × ULN, with an endogenous creatinine clearance rate > 60 mL/min (calculated using the Cockcroft-Gault formula). Coagulation: Prothrombin time (PT)/international normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless the patient is receiving anticoagulant therapy, in which case PT or aPTT must be within the expected therapeutic range for the anticoagulant used).
  6. Life expectancy ≥ 3 months.
  7. Adequate understanding of the study, ability to complete treatment, suitability for follow-up, and voluntary provision of written informed consent.

Exclusion Criteria:

  1. Presence of small cell carcinoma components in the histological examination results.
  2. Co-occurrence of EGFR mutation, ALK rearrangement, or ROS-1 rearrangement positivity.
  3. History of other primary malignancies, with the following exceptions: Malignancies treated with curative intent with no known active disease and low potential for recurrence for ≥5 years prior to the first dose of investigational product (IP); adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; or adequately treated carcinoma in situ without evidence of disease.
  4. Active or documented history of autoimmune or inflammatory diseases (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [excluding diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, granulomatosis with polyangiitis [Wegener's syndrome], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.).
  5. History of allogeneic organ transplantation.
  6. History of active primary immunodeficiency.
  7. Presence of uncontrolled concurrent illness, including but not limited to persistent or active infection (including tuberculosis, hepatitis B, hepatitis C, human immunodeficiency virus [HIV], etc.), symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease (ILD), severe chronic gastrointestinal disease associated with diarrhea, or psychiatric disorders/social situations that would limit compliance with study requirements, substantially increase the risk of adverse events (AEs), or compromise the patient's ability to provide written informed consent.
  8. Female patients who are pregnant or breastfeeding.
  9. Concurrent or prior use of immunosuppressive medication within 14 days prior to the first dose of induction immunotherapy. Exceptions include: intranasal, inhaled, or topical corticosteroids, or local corticosteroid injections (e.g., intra-articular injection); systemic corticosteroids at physiological doses not exceeding 10 mg/day of prednisone or its equivalent; corticosteroids as prophylactic premedication for hypersensitivity reactions (e.g., premedication for computed tomography [CT] scan); or systemic corticosteroid administration administered as part of chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC), or administered prophylactically or for the management of toxicity induced by chemotherapy and/or radiotherapy.
  10. Known allergy or hypersensitivity to any study drug or any excipient of a study drug.
  11. Patients judged by the investigator to be unable to comply with study procedures, restrictions, and requirements.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Arm 1(Phase I):Phase I Safety Lead-in (CI-CCRT-I)
Phase I safety lead-in cohort. Participants receive induction chemoimmunotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy to evaluate treatment safety and tolerability.
Platinum-based doublet chemotherapy combined with a PD-1 inhibitor administered every 3 weeks for 2 cycles in the CI-CCRT-I cohort and 3 cycles in the carbon-ion radiotherapy cohort.
Definitive thoracic radiotherapy delivered to the primary tumor and involved lymph nodes with concurrent platinum-based chemotherapy. Radiotherapy is administered at 50-60 Gy in 25-30 fractions using intensity-modulated radiotherapy techniques.
PD-1 inhibitor administered every 3 weeks after completion of radiotherapy for up to 1 year or until disease progression, unacceptable toxicity, or withdrawal of consent.
Eksperimentel: Arm 2(Phase II Cohort A):Conventional Radiotherapy Cohort
Participants considered suitable for definitive thoracic radiotherapy receive induction chemoimmunotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy.
Platinum-based doublet chemotherapy combined with a PD-1 inhibitor administered every 3 weeks for 2 cycles in the CI-CCRT-I cohort and 3 cycles in the carbon-ion radiotherapy cohort.
Definitive thoracic radiotherapy delivered to the primary tumor and involved lymph nodes with concurrent platinum-based chemotherapy. Radiotherapy is administered at 50-60 Gy in 25-30 fractions using intensity-modulated radiotherapy techniques.
PD-1 inhibitor administered every 3 weeks after completion of radiotherapy for up to 1 year or until disease progression, unacceptable toxicity, or withdrawal of consent.
Eksperimentel: Arm 3(Phase II Cohort B):Carbon-Ion Radiotherapy Cohort
Participants with excessive tumor burden or unfavorable dosimetric parameters for conventional thoracic radiotherapy receive induction chemoimmunotherapy followed by carbon-ion radiotherapy and consolidation immunotherapy.
Platinum-based doublet chemotherapy combined with a PD-1 inhibitor administered every 3 weeks for 2 cycles in the CI-CCRT-I cohort and 3 cycles in the carbon-ion radiotherapy cohort.
PD-1 inhibitor administered every 3 weeks after completion of radiotherapy for up to 1 year or until disease progression, unacceptable toxicity, or withdrawal of consent.
Carbon-ion radiotherapy delivered to the primary tumor and involved lymph nodes for patients unsuitable for conventional definitive thoracic radiotherapy because of excessive tumor burden or unfavorable dosimetric parameters.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Progression-Free Survival (PFS)
Tidsramme: Up to 36 months
Progression-free survival is defined as the time from treatment initiation to documented disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first.
Up to 36 months
Incidence of Grade 3 or Higher Treatment-Related Adverse Events
Tidsramme: From treatment initiation through 6 months after completion of radiotherapy
Treatment-related adverse events assessed according to CTCAE version 6.0.
From treatment initiation through 6 months after completion of radiotherapy

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Overall Survival (OS)
Tidsramme: Up to 60 months
Overall survival is defined as the time from treatment initiation to death from any cause.
Up to 60 months
Objective Response Rate (ORR)
Tidsramme: From baseline through 24 months
Objective response rate is defined as the proportion of participants achieving complete response (CR) or partial response (PR) according to RECIST version 1.1.
From baseline through 24 months
Treatment Completion Rate
Tidsramme: Up to 18 months
Proportion of participants who successfully complete the planned induction chemoimmunotherapy, radiotherapy-based treatment (concurrent chemoradiotherapy or carbon-ion radiotherapy), and consolidation immunotherapy according to protocol requirements.
Up to 18 months
Local Control Rate
Tidsramme: Up to 36 months
Local control rate is defined as the proportion of participants without locoregional disease progression according to RECIST version 1.1 and investigator assessment.
Up to 36 months

Andre resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Predictive Value of Minimal Residual Disease (MRD) for Clinical Outcomes
Tidsramme: From baseline through 36 months
To evaluate whether baseline and dynamic changes in minimal residual disease (MRD) status are associated with treatment response, progression-free survival, and overall survival in participants receiving combined radiotherapy and immunotherapy.
From baseline through 36 months
Predictive Value of Radiomics for Clinical Outcomes
Tidsramme: From baseline through 36 months
To evaluate whether radiomic features derived from imaging studies are associated with treatment response, progression-free survival, and overall survival in participants receiving combined radiotherapy and immunotherapy.
From baseline through 36 months

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Samarbejdspartnere

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

9. oktober 2022

Primær færdiggørelse (Faktiske)

30. maj 2026

Studieafslutning (Anslået)

30. november 2027

Datoer for studieregistrering

Først indsendt

3. juni 2026

Først indsendt, der opfyldte QC-kriterier

3. juni 2026

Først opslået (Faktiske)

8. juni 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

8. juni 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

3. juni 2026

Sidst verificeret

1. juni 2026

Mere information

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