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

2026년 6월 3일 업데이트: 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.

연구 개요

상세 설명

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.

연구 유형

중재적

등록 (실제)

30

단계

  • 2 단계
  • 1단계

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연구 장소

    • Xuhui
      • Shanghai, Xuhui, 중국, 200052
        • Shanghai Chest Hospital

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

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설명

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.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위화되지 않음
  • 중재 모델: 병렬 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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.
실험적: 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.
실험적: 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.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Progression-Free Survival (PFS)
기간: 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
기간: 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

2차 결과 측정

결과 측정
측정값 설명
기간
Overall Survival (OS)
기간: 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)
기간: 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
기간: 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
기간: 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

기타 결과 측정

결과 측정
측정값 설명
기간
Predictive Value of Minimal Residual Disease (MRD) for Clinical Outcomes
기간: 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
기간: 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

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일반 간행물

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2022년 10월 9일

기본 완료 (실제)

2026년 5월 30일

연구 완료 (추정된)

2027년 11월 30일

연구 등록 날짜

최초 제출

2026년 6월 3일

QC 기준을 충족하는 최초 제출

2026년 6월 3일

처음 게시됨 (실제)

2026년 6월 8일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 6월 8일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 6월 3일

마지막으로 확인됨

2026년 6월 1일

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