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Neoadjuvant Toripalimab for Non-squamous NSCLC With EGFR Mutation

Primary Purpose

Non Squamous Non Small Cell Lung Cancer, EGFR Positive Non-small Cell Lung Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Toripalimab plus Chemotherapy
Sponsored by
Peking University People's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non Squamous Non Small Cell Lung Cancer focused on measuring Non squamous non small cell lung cancer, EGFR Mutation, Neoadjuvant immuno-chemotherapy, Predictive and prognostic biomarker

Eligibility Criteria

17 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Provision of signed informed consent by the patient or legally acceptable representative; Previously untreated, histologically confirmed resectable stage II-IIIA, IIIB(N2) (AJCC staging 8th edition) non-squamous non-small cell lung cancer; Adequate tissue samples for PD-L1 immunohistochemical testing and gene mutations test by RT-pCR or NGS, or consent for blood RT-PCR or NGS if tissue samples are insufficient; Harboring EGFR mutation (19del or L858R); Aged 18-70 years, regardless of gender; Eastern Cooperative Group (ECOG) Performance Status 0-1; Acceptable cardiac function with a left ventricular ejection fraction >50%; Acceptable respiratory function (FEV1>1.5L, DLCO>50%) and ability to tolerate radical lung cancer surgery; Acceptable bone marrow haematopoiesis with leucocytes ≥ 4 x 10^9/L, neutrophils ≥ 1.5 x 10^9/L, haemoglobin ≥ 10g/dL and platelets ≥ 100 x 10^9/L; Acceptable renal function with a glomerular filtration rate ≥ 60 mL/min; Acceptable liver function with total bilirubin ≤ 1.5 x ULN, AST ≤ 3 x ULN, and ALT ≤ 3 x ULN; Presence of measurable lesions as defined by RECIST 1.1 criteria; Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 3 days prior to the start of study treatment, and agree to use effective contraception for the duration of study drug use and for 120 days after the last dose. Women of childbearing potential were defined as sexually mature females who 1) had not undergone hysterectomy or bilateral oophorectomy and 2) had not experienced spontaneous menopause for 12 consecutive months (amenorrhea after cancer treatment did not preclude fertility) (menstruation had occurred at any time during the previous 12 consecutive months). Exclusion Criteria: Pathological histologically confirmed small cell lung cancer, squamous epithelial cell carcinoma and other pathological subtypes cannot be enrolled; Patients with advanced or metastatic lung cancer, or unresectable lung cancer, or who have received previous systemic anti-tumour therapy such as immunotherapy, chemotherapy or targeted therapy cannot be enrolled; Patients with a history of active autoimmune disease or autoimmune disease that is likely to recur cannot be enrolled; Patients with active hepatitis B and C requiring relevant antiviral therapy need to have HBV-DNA <500 IU/ml and have been on anti-HBV treatment for at least 14 days prior to study entry and continue treatment during the treatment period; HCV RNA-positive patients should be excluded; Patients who are allergic to chemotherapeutic agents such as carboplatin, paclitaxel, albumin paclitaxel, pemetrexed; Patients with a history of allergy to monoclonal antibody drugs; Patients who have previously received an allogeneic stem cell transplant or organ transplant; Patients with mental illness or any other illness that makes it impossible to comply with treatment; Patients who are unable or unwilling to sign the informed consent form; Patients with comorbidities or other conditions that, in the opinion of the investigator, may affect compliance with the protocol or make them unsuitable for participation in this study.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    19DEL cohort

    L858R cohort

    Arm Description

    Patients who participated in the trial with EGFR 19DEL mutation will be included in this arm.

    Patients who participated in the trial with EGFR L858R mutation will be included in this arm

    Outcomes

    Primary Outcome Measures

    Pathologic Complete Response (pCR) Rate
    Pathologic complete response (pCR) rate is defined as the percentage of participants with no residual viable tumor in lung primary or lymph nodes as evaluated by blinded independent pathological review (BIPR).

    Secondary Outcome Measures

    Major Pathologic Response (MPR) Rate
    Major pathologic response (MPR) rate is defined as the percentage of participants with less than or equal to 10% of residual viable tumor in lung primary or lymph nodes as evaluated by blinded independent pathological review (BIPR). Viable tumors in situ carcinoma should not be included in MPR calculation.
    Pathologic Complete Response (pCR) Rate in non-squamous NSCLC with different EGFR mutations status
    Assessing pCR rates in the 19del and L858R groups separately.
    Major Pathologic Response (MPR) Rate in non-squamous NSCLC with different EGFR mutations status
    Assessing MRP rates in the 19del and L858R groups separately.
    Pathologic Complete Response (pCR) Rate in non-squamous NSCLC with different PD-L1 expression levels
    Assessing pCR rates in the PD-L1 TPS≥1% and PD-L1 TPS<1% groups separately.
    Major Pathologic Response (MPR) Rate in non-squamous NSCLC with different PD-L1 expression levels
    Assessing MRP rates in the PD-L1 TPS≥1% and PD-L1 TPS<1% groups separately.
    Event-free Survival (EFS)
    EFS is defined as the time from participation to any of the following events: progression of disease, recurrence disease, or death due to any cause. Progression/recurrence will be assessed either by biopsy assessed by local pathologist or by investigator-assessed imaging using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
    The Safety and Tolerability
    To assess the safety and tolerability of neoadjuvant immuno-chemotherapy in patients with resectable stage II-IIIB non-squamous non-small cell lung cancer harboring EGFR mutations, including as follows: number, frequency and proportion of patients with adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI) and on-study deaths.

    Full Information

    First Posted
    July 10, 2023
    Last Updated
    July 28, 2023
    Sponsor
    Peking University People's Hospital
    Collaborators
    Shanghai Junshi Bioscience Co., Ltd.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05962021
    Brief Title
    Neoadjuvant Toripalimab for Non-squamous NSCLC With EGFR Mutation
    Official Title
    Neoadjuvant Toripalimab Plus Chemotherapy for Resectable Stage II-IIIB Non-squamous Non-small Cell Lung Cancer With EGFR Mutation: a Multicentre, Multi-cohort, Exploratory Study.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    August 1, 2023 (Anticipated)
    Primary Completion Date
    June 30, 2026 (Anticipated)
    Study Completion Date
    June 30, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Peking University People's Hospital
    Collaborators
    Shanghai Junshi Bioscience Co., Ltd.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This study was designed to investigate the efficacy and safety of neoadjuvant Toripalimab (anti-PD1) plus chemotherapy for patients with resectable II-IIIB non-squamous NSCLC harboring EGFR mutation, and to explore the potential predictive and prognostic biomarkers, aiming to provide more abundant evidences for the preoperative treatment decision of non-squamous NSCLC patients.
    Detailed Description
    Previous studies have confirmed the efficacy of neoadjuvant immunotherapy in NSCLC patients without driver gene mutation, while its efficacy in driver gene mutated patients is still controversial. This study was designed to investigate the efficacy and safety of neoadjuvant Toripalimab (anti-PD1) plus chemotherapy for patients with resectable II-IIIB non-squamous NSCLC harboring EGFR mutation, and to explore the potential predictive and prognostic biomarkers, aiming to provide more abundant evidences for the preoperative treatment decision of non-squamous NSCLC patients.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Non Squamous Non Small Cell Lung Cancer, EGFR Positive Non-small Cell Lung Cancer
    Keywords
    Non squamous non small cell lung cancer, EGFR Mutation, Neoadjuvant immuno-chemotherapy, Predictive and prognostic biomarker

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Model Description
    Patients were divided into the 19del and L858R groups according to their EGFR mutation status.
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    126 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    19DEL cohort
    Arm Type
    Experimental
    Arm Description
    Patients who participated in the trial with EGFR 19DEL mutation will be included in this arm.
    Arm Title
    L858R cohort
    Arm Type
    Experimental
    Arm Description
    Patients who participated in the trial with EGFR L858R mutation will be included in this arm
    Intervention Type
    Drug
    Intervention Name(s)
    Toripalimab plus Chemotherapy
    Intervention Description
    Therapy was administered on a 21-day regimen for 3 cycles, with Toripalimab (240mg, d1), carboplatin (AUC=5, d1) + pemetrexed (500 mg/m2, d1) for patients with lung adenocarcinoma and carboplatin (AUC=5, d1) + albumin-bound paclitaxel (260 mg/m2, d1) for patients with other subtypes.
    Primary Outcome Measure Information:
    Title
    Pathologic Complete Response (pCR) Rate
    Description
    Pathologic complete response (pCR) rate is defined as the percentage of participants with no residual viable tumor in lung primary or lymph nodes as evaluated by blinded independent pathological review (BIPR).
    Time Frame
    Within 1 week after surgery
    Secondary Outcome Measure Information:
    Title
    Major Pathologic Response (MPR) Rate
    Description
    Major pathologic response (MPR) rate is defined as the percentage of participants with less than or equal to 10% of residual viable tumor in lung primary or lymph nodes as evaluated by blinded independent pathological review (BIPR). Viable tumors in situ carcinoma should not be included in MPR calculation.
    Time Frame
    Within 1 week after surgery
    Title
    Pathologic Complete Response (pCR) Rate in non-squamous NSCLC with different EGFR mutations status
    Description
    Assessing pCR rates in the 19del and L858R groups separately.
    Time Frame
    Within 1 week after surgery
    Title
    Major Pathologic Response (MPR) Rate in non-squamous NSCLC with different EGFR mutations status
    Description
    Assessing MRP rates in the 19del and L858R groups separately.
    Time Frame
    Within 1 week after surgery
    Title
    Pathologic Complete Response (pCR) Rate in non-squamous NSCLC with different PD-L1 expression levels
    Description
    Assessing pCR rates in the PD-L1 TPS≥1% and PD-L1 TPS<1% groups separately.
    Time Frame
    Within 1 week after surgery
    Title
    Major Pathologic Response (MPR) Rate in non-squamous NSCLC with different PD-L1 expression levels
    Description
    Assessing MRP rates in the PD-L1 TPS≥1% and PD-L1 TPS<1% groups separately.
    Time Frame
    Within 1 week after surgery
    Title
    Event-free Survival (EFS)
    Description
    EFS is defined as the time from participation to any of the following events: progression of disease, recurrence disease, or death due to any cause. Progression/recurrence will be assessed either by biopsy assessed by local pathologist or by investigator-assessed imaging using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
    Time Frame
    Up to 24 months after participation
    Title
    The Safety and Tolerability
    Description
    To assess the safety and tolerability of neoadjuvant immuno-chemotherapy in patients with resectable stage II-IIIB non-squamous non-small cell lung cancer harboring EGFR mutations, including as follows: number, frequency and proportion of patients with adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI) and on-study deaths.
    Time Frame
    Up to 24 months after participation

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    17 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Provision of signed informed consent by the patient or legally acceptable representative; Previously untreated, histologically confirmed resectable stage II-IIIA, IIIB(N2) (AJCC staging 8th edition) non-squamous non-small cell lung cancer; Adequate tissue samples for PD-L1 immunohistochemical testing and gene mutations test by RT-pCR or NGS, or consent for blood RT-PCR or NGS if tissue samples are insufficient; Harboring EGFR mutation (19del or L858R); Aged 18-70 years, regardless of gender; Eastern Cooperative Group (ECOG) Performance Status 0-1; Acceptable cardiac function with a left ventricular ejection fraction >50%; Acceptable respiratory function (FEV1>1.5L, DLCO>50%) and ability to tolerate radical lung cancer surgery; Acceptable bone marrow haematopoiesis with leucocytes ≥ 4 x 10^9/L, neutrophils ≥ 1.5 x 10^9/L, haemoglobin ≥ 10g/dL and platelets ≥ 100 x 10^9/L; Acceptable renal function with a glomerular filtration rate ≥ 60 mL/min; Acceptable liver function with total bilirubin ≤ 1.5 x ULN, AST ≤ 3 x ULN, and ALT ≤ 3 x ULN; Presence of measurable lesions as defined by RECIST 1.1 criteria; Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 3 days prior to the start of study treatment, and agree to use effective contraception for the duration of study drug use and for 120 days after the last dose. Women of childbearing potential were defined as sexually mature females who 1) had not undergone hysterectomy or bilateral oophorectomy and 2) had not experienced spontaneous menopause for 12 consecutive months (amenorrhea after cancer treatment did not preclude fertility) (menstruation had occurred at any time during the previous 12 consecutive months). Exclusion Criteria: Pathological histologically confirmed small cell lung cancer, squamous epithelial cell carcinoma and other pathological subtypes cannot be enrolled; Patients with advanced or metastatic lung cancer, or unresectable lung cancer, or who have received previous systemic anti-tumour therapy such as immunotherapy, chemotherapy or targeted therapy cannot be enrolled; Patients with a history of active autoimmune disease or autoimmune disease that is likely to recur cannot be enrolled; Patients with active hepatitis B and C requiring relevant antiviral therapy need to have HBV-DNA <500 IU/ml and have been on anti-HBV treatment for at least 14 days prior to study entry and continue treatment during the treatment period; HCV RNA-positive patients should be excluded; Patients who are allergic to chemotherapeutic agents such as carboplatin, paclitaxel, albumin paclitaxel, pemetrexed; Patients with a history of allergy to monoclonal antibody drugs; Patients who have previously received an allogeneic stem cell transplant or organ transplant; Patients with mental illness or any other illness that makes it impossible to comply with treatment; Patients who are unable or unwilling to sign the informed consent form; Patients with comorbidities or other conditions that, in the opinion of the investigator, may affect compliance with the protocol or make them unsuitable for participation in this study.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Fan Yang, M.D.
    Phone
    +86-010-88326657
    Email
    yangfan@pkuph.edu.cn
    First Name & Middle Initial & Last Name or Official Title & Degree
    Xiang Yan, M.D.
    Phone
    +86-13581786750
    Email
    yxiang301@sina.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Fan Yanf, M.D.
    Organizational Affiliation
    Peking University People's Hospital
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

    Learn more about this trial

    Neoadjuvant Toripalimab for Non-squamous NSCLC With EGFR Mutation

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