Locally Advanced Non-Small Cell Lung Cancer, Non-Small Cell Lung Cancer, Unresectable Stage III NSCLC
Conditions
Keywords
NSCLC, Stage III NSCLC, Unresectable NSCLC, Concurrent Chemoradiotherapy, Consolidation Immunotherapy, Chemoimmunotherapy, Carbon-Ion Radiotherapy, PD-1 Inhibitor, PACIFIC Regimen
Brief summary
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.
Detailed description
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.
Interventions
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.
RADIATIONConcurrent chemoradiotherapy (cCRT)
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.
RADIATIONCarbon-Ion Radiotherapy
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.
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.
Sponsors
Shanghai Chest Hospital
RenJi Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an open-label multicenter phase I/II study with sequential cohort assignment. Phase I consists of a single-arm safety lead-in cohort (CI-CCRT-I) evaluating induction chemoimmunotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy. After safety evaluation, phase II expands into tumor-extent stratified treatment cohorts according to radiotherapy feasibility assessment, including conventional chemoradiotherapy-based treatment and carbon-ion radiotherapy-based treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | 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. |
| Incidence of Grade 3 or Higher Treatment-Related Adverse Events | From treatment initiation through 6 months after completion of radiotherapy | Treatment-related adverse events assessed according to CTCAE version 6.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 60 months | Overall survival is defined as the time from treatment initiation to death from any cause. |
| Objective Response Rate (ORR) | 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. |
| Treatment Completion Rate | 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. |
| Local Control Rate | 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. |
Countries
China
Outcome results
None listed