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

2026. július 22. frissítette: 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

PIVOT study is a multicenter, phase I/II clinical study designed to evaluate induction chemoimmunotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy in patients with unresectable locally advanced non-small cell lung cancer (NSCLC). Phase I consists of a single-arm safety lead-in study evaluating the safety and preliminary efficacy of the investigational regimen. If predefined safety criteria are met, the study proceeds to a phase II randomized controlled trial comparing induction chemoimmunotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy with the standard PACIFIC regimen. The objective of the phase II study is to determine whether the investigational treatment strategy improves progression-free survival while maintaining an acceptable safety profile compared with the standard PACIFIC regimen.

A tanulmány áttekintése

Részletes leírás

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 the integration of 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.We also hypothesize that induction chemoimmunotherapy can achieve early immune activation, thereby enhancing the synergy between subsequent chemoradiotherapy and immunotherapy and potentially improving the survival outcomes of the current PACIFIC treatment paradigm.

This multicenter phase I/II study consists of two sequential parts. The phase I portion is designed as a single-arm safety lead-in study evaluating induction chemoimmunotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy. If predefined safety criteria are met, the study proceeds to a phase II randomized, open-label, parallel-group trial in which eligible participants are randomized in a 1:1 ratio to receive either induction chemoimmunotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy or the standard PACIFIC regimen consisting of concurrent chemoradiotherapy followed by consolidation immunotherapy. Randomization is stratified by disease stage (IIIA vs. IIIB/IIIC) and PD-L1 tumor cell expression (<1% vs. ≥1%). The objective of this study is to determine whether the addition of induction chemoimmunotherapy to the standard PACIFIC treatment strategy improves progression-free survival while maintaining an acceptable safety profile.

For the phase I safety lead-in study, the co-primary endpoints are treatment safety, assessed by the incidence of grade 3 or higher treatment-related adverse events, and progression-free survival (PFS). For the phase II randomized study, the primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), objective response rate (ORR), treatment completion rate, local control rate, and treatment-related adverse events. Exploratory analyses include evaluation of minimal residual disease (MRD) to determine whether baseline and dynamic changes in MRD status are associated with treatment response, progression-free survival, and overall survival in participants receiving combined radiotherapy and immunotherapy.

Tanulmány típusa

Beavatkozó

Beiratkozás (Becsült)

108

Fázis

  • 2. fázis
  • 1. fázis

Kapcsolatok és helyek

Ez a rész a vizsgálatot végzők elérhetőségeit, valamint a vizsgálat lefolytatásának helyére vonatkozó információkat tartalmazza.

Tanulmányi kapcsolat

Tanulmányi helyek

    • Xuhui
      • Shanghai, Xuhui, Kína, 200030
        • Toborzás
        • Shanghai Chest Hospital
        • Kapcsolatba lépni:
        • Kutatásvezető:
          • Wen Yu, MD

Részvételi kritériumok

A kutatók olyan embereket keresnek, akik megfelelnek egy bizonyos leírásnak, az úgynevezett jogosultsági kritériumoknak. Néhány példa ezekre a kritériumokra a személy általános egészségi állapota vagy a korábbi kezelések.

Jogosultsági kritériumok

Tanulmányozható életkorok

  • Felnőtt
  • Idősebb felnőtt

Egészséges önkénteseket fogad

Nem

Leírás

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.

Tanulási terv

Ez a rész a vizsgálati terv részleteit tartalmazza, beleértve a vizsgálat megtervezését és a vizsgálat mérését.

Hogyan készül a tanulmány?

Tervezési részletek

  • Elsődleges cél: Kezelés
  • Kiosztás: Véletlenszerűsített
  • Beavatkozó modell: Párhuzamos hozzárendelés
  • Maszkolás: Nincs (Open Label)

Fegyverek és beavatkozások

Résztvevő csoport / kar
Beavatkozás / kezelés
Kísérleti: Phase I Safety Lead-in Cohort/Phase II Experimental Arm (CI-CCRT-I Strategy)
Participants will receive induction chemoimmunotherapy followed by definitive concurrent chemoradiotherapy and consolidation immunotherapy. Induction treatment consists of two cycles (2-4 cycles in phase I cohort) of platinum-based chemotherapy combined with PD-L1 inhibitor prior to concurrent chemoradiotherapy. Participants without disease progression after concurrent chemoradiotherapy will subsequently receive consolidation PD-L1 inhibitor for up to one year or until disease progression or unacceptable toxicity.
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.
Phase I: Patients received platinum-based doublet chemotherapy plus a PD-L1 inhibitor every 3 weeks for 2-4 cycles. Phase II (experimental group): Patients received platinum-based doublet chemotherapy plus a PD-L1 inhibitor every 3 weeks for 2 cycles.
PD-L1 inhibitor administered every 3 weeks after completion of radiotherapy for up to 1 year or until disease progression, unacceptable toxicity, or withdrawal of consent.
Aktív összehasonlító: Phase II Control Arm (PACIFIC Strategy)
Participants will receive definitive concurrent chemoradiotherapy followed by consolidation PD-L1 inhibitor according to the standard PACIFIC treatment strategy. Participants without disease progression after concurrent chemoradiotherapy will receive consolidation PD-L1 inhibitor for up to one year or until disease progression or unacceptable toxicity.
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-L1 inhibitor administered every 3 weeks after completion of radiotherapy for up to 1 year or until disease progression, unacceptable toxicity, or withdrawal of consent.

Mit mér a tanulmány?

Elsődleges eredményintézkedések

Eredménymérő
Intézkedés leírása
Időkeret
Progression-Free Survival (PFS)
Időkeret: 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
Időkeret: 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

Másodlagos eredményintézkedések

Eredménymérő
Intézkedés leírása
Időkeret
Overall Survival (OS)
Időkeret: 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)
Időkeret: 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
Időkeret: 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
Időkeret: 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

Egyéb eredményintézkedések

Eredménymérő
Intézkedés leírása
Időkeret
Predictive Value of Minimal Residual Disease (MRD) for Clinical Outcomes
Időkeret: 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

Együttműködők és nyomozók

Itt találhatja meg a tanulmányban érintett személyeket és szervezeteket.

Publikációk és hasznos linkek

A vizsgálattal kapcsolatos információk beviteléért felelős személy önkéntesen bocsátja rendelkezésre ezeket a kiadványokat. Ezek bármiről szólhatnak, ami a tanulmányhoz kapcsolódik.

Általános kiadványok

Tanulmányi rekorddátumok

Ezek a dátumok nyomon követik a ClinicalTrials.gov webhelyre benyújtott vizsgálati rekordok és összefoglaló eredmények benyújtásának folyamatát. A vizsgálati feljegyzéseket és a jelentett eredményeket a Nemzeti Orvostudományi Könyvtár (NLM) felülvizsgálja, hogy megbizonyosodjon arról, hogy megfelelnek-e az adott minőség-ellenőrzési szabványoknak, mielőtt közzéteszik őket a nyilvános weboldalon.

Tanulmány főbb dátumok

Tanulmány kezdete (Tényleges)

2022. október 9.

Elsődleges befejezés (Becsült)

2028. december 31.

A tanulmány befejezése (Becsült)

2028. december 31.

Tanulmányi regisztráció dátumai

Először benyújtva

2026. június 3.

Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak

2026. június 3.

Első közzététel (Tényleges)

2026. június 8.

Tanulmányi rekordok frissítései

Utolsó frissítés közzétéve (Tényleges)

2026. július 23.

Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak

2026. július 22.

Utolsó ellenőrzés

2026. július 1.

Több információ

A tanulmányhoz kapcsolódó kifejezések

Terv az egyéni résztvevői adatokhoz (IPD)

Tervezi megosztani az egyéni résztvevői adatokat (IPD)?

NEM

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