Induction Chemotherapy and Toripalimab Followed by Chemoradiotherapy for Large-volume Local Advanced NSCLC

Study Overview
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Brief Summary
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This study is a Phase II study to evaluate the clinical efficacy and safety of Toripalimab combined with chemoradiotherapy for large-volume local advanced non-small cell lung cancer

Detailed Description
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This study is a Phase II study to evaluate the clinical efficacy and safety of two cycles of induction Toripalimab plus chemotherapy followed by definitive chemoradiotherapy and consolidation Toripalimab therapy for large-volume, unresectable, locally advanced stage II-III non-small cell lung cancer (large volume is defined as primary tumor ≥5 cm in greatest dimension or metastatic lymph nodes ≥2 cm in shortest diameter).

Official Title
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The Efficacy and Safety of Induction Chemotherapy and Toripalimab Followed by Chemoradiotherapy for Large-volume (Bulky) Local Advanced Non-small Cell Lung Cancer

Conditions
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Local Advanced Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Toripalimab
* Radiation: Concurrent chemoradiation therapy and consolidation immunotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 years; ECOG score 0-2. Histologically or cytologically confirmed non-small cell lung cancer (NSCLC). Unresectable Stage II-III NSCLC (according to AJCC 8th edition) with maximum tumor diameter T ≥ 5 cm in the primary tumor or minimum diameter N ≥ 2 cm in mediastinal metastatic lymph nodes. No other previous anti-tumor history, at least 3 months of expected survival. No serious medical diseases and dysfunction of major organs, such as blood routine, liver, kidney, heart and lung function. Exclusion Criteria: Pathologic type was adenocarcinoma with EGFR gene mutation or ALK gene rearrangement. Patients with other active malignancies within 5 years or at the same time. Active or previously documented autoimmune or inflammatory diseases (including inflammatory bowel disease, diverticulitis [except diverticular disease], systemic lupus erythematosus, Sarcoidosis syndrome, Wegener' s syndrome). History of allogeneic organ transplantation. History of active primary immunodeficiency. Patients with uncontrolled concurrent diseases, including but not limited to persistent or active infection (including tuberculosis, hepatitis B, hepatitis C, human immunodeficiency virus, etc.), symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled arrhythmia, active interstitial lung disease, severe chronic gastrointestinal disease with diarrhea or mental illness. Women of child-bearing potential who are pregnant or breastfeeding. Allergic to research drug ingredients. Ongoing or prior use of immunosuppressive agents within 14 days prior to first dose The investigator judged other situations not suitable for inclusion in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Induction Toripalimab and chemotherapy followed by concurrent chemoradiotherapy<br>Participants will receive 2 cycles of induction therapy of platinum-based chemotherapy combined with Toripalimab, followed by platinum-based concurrent chemoradiation. Then participants will receive Toripalimab consolidation therapy after chemoradiotherapy with maximum 1 years or until disease progression or intolerable toxicity. | Drug: Toripalimab<br>* Two cycles of induction Toripalimab (240mg every 3 weeks) plus platinum-based doublet chemotherapy as induction chemoimmunotherapy.<br>* Other names: Tuo Yi;Radiation: Concurrent chemoradiation therapy and consolidation immunotherapy<br>* Thoracic radiation therapy (54-66Gy/25-33F/5-7week), concurrently with platinum-based doublet chemotherapy, followed by consolidation Toripalimab (240mg every 3 weeks) as consolidation immunotherapy for up to 12 months.<br>* Other names: The PACIFIC regimen;|
| Active Comparator: Induction chemotherapy followed by concurrent chemoradiotherapy<br>Participants will receive 2 cycles of induction platinum-based chemotherapy, followed by platinum-based concurrent chemoradiation. Then participants will receive Toripalimab consolidation therapy after chemoradiotherapy with maximum 1 years or until disease progression or intolerable toxicity. | Radiation: Concurrent chemoradiation therapy and consolidation immunotherapy<br>* Thoracic radiation therapy (54-66Gy/25-33F/5-7week), concurrently with platinum-based doublet chemotherapy, followed by consolidation Toripalimab (240mg every 3 weeks) as consolidation immunotherapy for up to 12 months.<br>* Other names: The PACIFIC regimen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Defined as the time from date of recruitment until the date of first documented progression or date of death from any cause, whichever came first. | From date of recruitment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS） | Defined as the time from recruitment to the date of any documented death due to any cause. | From recruitment to the date of any documented death due to any cause, assessed up to 36 months. | 
| Adverse Event | The incidence of adverse events (AEs) and serious adverse events (SAEs), evaluated by CTCAE 5.0. Appropriate description of AEs and laboratory data/vital signs will be produced. Number of patients who had at least one adverse event will be calculated. | AEs and SAEs must be collected from the time that the main study informed consent is obtained to 28 days after discontinuation of study drug, up to 36 months. | 
| Objective Tumour Response (ORR) | The objective tumour response (ORR) will be calculated as the number of patients with CR or PR per RECIST Criteria. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Tumor assessment using RECIST will be performed at baseline then every 42 days (6 weeks) ± 7 days (1 week) from recruitment until objective progression or death from any cause, assessed up to 36 months. | 
| Disease control rate（DCR） | DCR will be calculated as the number of patients with CR, PR or sustained SD≥6 weeks per RECIST Criteria. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase. | Tumour assessment using RECIST will be performed at baseline then every 42 days (6 weeks) ± 7 days (1 week) from randomisation until objective progression or death from any cause, assessed up to 36 months. |