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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small Cell Lung Cancer; Unresectable Stage III NSCLC; Locally Advanced Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Induction chemoimmunotherapy; Radiation: Concurrent chemoradiotherapy (cCRT); Drug: consolidation immunotherapy; Radiation: Carbon-Ion Radiotherapy

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Xuhui
    • Shanghai, Xuhui, China, 200052
      • Shanghai Chest Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Induction chemoimmunotherapy; 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.; Radiation: Concurrent 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.; Drug: consolidation immunotherapy; 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.
Experimental: 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.	Drug: Induction chemoimmunotherapy; 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.; Radiation: Concurrent 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.; Drug: consolidation immunotherapy; 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.
Experimental: 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.	Drug: Induction chemoimmunotherapy; 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.; Drug: consolidation immunotherapy; 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.; Radiation: Carbon-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	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	Treatment-related adverse events assessed according to CTCAE version 6.0.	From treatment initiation through 6 months after completion of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall survival is defined as the time from treatment initiation to death from any cause.	Up to 60 months
Objective Response Rate (ORR)	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	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	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive Value of Minimal Residual Disease (MRD) for Clinical Outcomes	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	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

Collaborators and Investigators

• Sponsor: Shanghai Chest Hospital
• Collaborators: RenJi Hospital

Publications and helpful links

General Publications

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.
• Jabbour SK, Lee KH, Frost N, Breder V, Kowalski DM, Pollock T, Levchenko E, Reguart N, Martinez-Marti A, Houghton B, Paoli JB, Safina S, Park K, Komiya T, Sanford A, Boolell V, Liu H, Samkari A, Keller SM, Reck M. Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. JAMA Oncol. 2021 Jun 4;7(9):1-9. doi: 10.1001/jamaoncol.2021.2301. Online ahead of print.
• Zhou Q, Chen M, Jiang O, Pan Y, Hu D, Lin Q, Wu G, Cui J, Chang J, Cheng Y, Huang C, Liu A, Yang N, Gong Y, Zhu C, Ma Z, Fang J, Chen G, Zhao J, Shi A, Lin Y, Li G, Liu Y, Wang D, Wu R, Xu X, Shi J, Liu Z, Cui N, Wang J, Wang Q, Zhang R, Yang J, Wu YL. Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):209-219. doi: 10.1016/S1470-2045(21)00630-6. Epub 2022 Jan 14.
• Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, Vansteenkiste JF, Garassino MC, Hui R, Quantin X, Rimner A, Wu YL, Ozguroglu M, Lee KH, Kato T, de Wit M, Kurata T, Reck M, Cho BC, Senan S, Naidoo J, Mann H, Newton M, Thiyagarajah P, Antonia SJ. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022 Apr 20;40(12):1301-1311. doi: 10.1200/JCO.21.01308. Epub 2022 Feb 2.
• Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. doi: 10.1093/jnci/djr325. Epub 2011 Sep 8.
• Wang Y, Zhang T, Wang J, Zhou Z, Liu W, Xiao Z, Deng L, Feng Q, Wang X, Lv J, Ma X, Xue Q, Wang J, Wang Z, Bi N. Induction Immune Checkpoint Inhibitors and Chemotherapy Before Definitive Chemoradiation Therapy for Patients With Bulky Unresectable Stage III Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2023 Jul 1;116(3):590-600. doi: 10.1016/j.ijrobp.2022.12.042. Epub 2023 Jan 7.
• Heymach JV, Harpole D, Mitsudomi T ea. AEGEAN: a phase 3 trial of neoadjuvant durvalumab + chemotherapy followed by adjuvant durvalumab in patients with resectable NSCLC. 2023 AACR Annual Meeting; April 14-19, 2023; Orlando, FL 2023;
• Wang C, Chen KN, Chen Q, Wu L, Wang Q, Li X, Ying K, Wang W, Zhao J, Liu L, Fu J, Zhang C, Liu J, Hu Y, Ntambwe I, Cai J, Bushong J, Tran P, Lu S. Neoadjuvant nivolumab plus chemotherapy versus chemotherapy for resectable NSCLC: subpopulation analysis of Chinese patients in CheckMate 816. ESMO Open. 2023 Dec;8(6):102040. doi: 10.1016/j.esmoop.2023.102040. Epub 2023 Nov 1.

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2022
• Primary Completion (Actual): May 30, 2026
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: June 3, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 8, 2026

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Chemoimmunotherapy; Unresectable NSCLC; Concurrent Chemoradiotherapy; PD-1 Inhibitor; Stage III NSCLC; Consolidation Immunotherapy; Carbon-Ion Radiotherapy; PACIFIC Regimen
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Therapeutics; Drug Therapy; Radiotherapy; Combined Modality Therapy; Chemoradiotherapy; Heavy Ion Radiotherapy
• Other Study ID Numbers: STRATUS-NSCLC-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No