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

NCT07632365 | Active Not Recruiting Phase 1

• 1 other identifier: STRATUS-NSCLC-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Small Cell Lung Cancer; Unresectable Stage III NSCLC; Locally Advanced Non-Small Cell Lung Cancer

Keywords

NSCLC; Stage III NSCLC; Unresectable NSCLC; Concurrent Chemoradiotherapy; Consolidation Immunotherapy; Chemoimmunotherapy; Carbon-Ion Radiotherapy; PD-1 Inhibitor; PACIFIC Regimen

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Overall Survival (OS)

  Up to 60 months

• Objective Response Rate (ORR)

  From baseline through 24 months

• Treatment Completion Rate

  Up to 18 months

• Local Control Rate

  Up to 36 months

Other Outcomes (2)

• Predictive Value of Minimal Residual Disease (MRD) for Clinical Outcomes

  From baseline through 36 months

• Predictive Value of Radiomics for Clinical Outcomes

  From baseline through 36 months

Study Arms (3)

Arm 1（Phase I）：Phase I Safety Lead-in (CI-CCRT-I)

EXPERIMENTAL

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; Radiation: Concurrent chemoradiotherapy (cCRT); Drug: consolidation immunotherapy

Arm 2（Phase II Cohort A）：Conventional Radiotherapy Cohort

EXPERIMENTAL

Participants considered suitable for definitive thoracic radiotherapy receive induction chemoimmunotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy.

Drug: Induction chemoimmunotherapy; Radiation: Concurrent chemoradiotherapy (cCRT); Drug: consolidation immunotherapy

Arm 3（Phase II Cohort B）：Carbon-Ion Radiotherapy Cohort

EXPERIMENTAL

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; Radiation: Carbon-Ion Radiotherapy; Drug: consolidation immunotherapy

Interventions

Induction chemoimmunotherapy DRUG

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.

Arm 1（Phase I）：Phase I Safety Lead-in (CI-CCRT-I); Arm 2（Phase II Cohort A）：Conventional Radiotherapy Cohort; Arm 3（Phase II Cohort B）：Carbon-Ion Radiotherapy Cohort

Concurrent chemoradiotherapy (cCRT) RADIATION

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.

Arm 1（Phase I）：Phase I Safety Lead-in (CI-CCRT-I); Arm 2（Phase II Cohort A）：Conventional Radiotherapy Cohort

Carbon-Ion Radiotherapy RADIATION

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.

Arm 3（Phase II Cohort B）：Carbon-Ion Radiotherapy Cohort

consolidation immunotherapy DRUG

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.

Arm 1（Phase I）：Phase I Safety Lead-in (CI-CCRT-I); Arm 2（Phase II Cohort A）：Conventional Radiotherapy Cohort; Arm 3（Phase II Cohort B）：Carbon-Ion Radiotherapy Cohort

Eligibility Criteria

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

You may qualify if:

• Age \>18 years, male or female, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC).
• Unresectable stage III NSCLC (according to the 8th edition of the AJCC staging system).
• No prior exposure to any other anti-tumor therapy.
• 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).
• Life expectancy ≥ 3 months.
• Adequate understanding of the study, ability to complete treatment, suitability for follow-up, and voluntary provision of written informed consent.

You may not qualify if:

• Presence of small cell carcinoma components in the histological examination results.
• Co-occurrence of EGFR mutation, ALK rearrangement, or ROS-1 rearrangement positivity.
• 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.
• 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.).
• History of allogeneic organ transplantation.
• History of active primary immunodeficiency.
• 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.
• Female patients who are pregnant or breastfeeding.
• 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.
• Known allergy or hypersensitivity to any study drug or any excipient of a study drug.
• Patients judged by the investigator to be unable to comply with study procedures, restrictions, and requirements.

Sponsors & Collaborators

• RenJi Hospital: collaborator
• Shanghai Chest Hospital: lead

Study Sites (1)

Shanghai Chest Hospital

Shanghai, Xuhui, 200052, China

Location

Related Publications (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.

  PMID: 36623605 BACKGROUND

• 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;

  BACKGROUND

• 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.

  PMID: 37922691 BACKGROUND

• 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.

  PMID: 34086039 BACKGROUND

• 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.

  PMID: 35038429 BACKGROUND

• 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.

  PMID: 35108059 BACKGROUND

• 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.

  PMID: 21903745 BACKGROUND

• 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.

  PMID: 33538338 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Chemoradiotherapy; Heavy Ion Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Director of Radiation Oncology Department

Model Details: 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.

Study Record Dates

• First Submitted: June 3, 2026
• First Posted: June 8, 2026
• Study Start: October 9, 2022
• Primary Completion: May 30, 2026
• Study Completion (Estimated): November 30, 2027
• Last Updated: June 8, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)