Clinical trial NCT05962021: 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
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: 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
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai Junshi Bioscience Co., Ltd.
First posted: 2023-07-27
Enrollment: 126
Sex: ALL
Minimum age (years): 17
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients were divided into the 19del and L858R groups according to their EGFR mutation status.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Provision of signed informed consent by the patient or legally acceptable representative;
2. Previously untreated, histologically confirmed resectable stage II-IIIA, IIIB(N2) (AJCC staging 8th edition) non-squamous non-small cell lung cancer;
3. 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;
4. Harboring EGFR mutation (19del or L858R);
5. Aged 18-70 years, regardless of gender;
6. Eastern Cooperative Group (ECOG) Performance Status 0-1;
7. Acceptable cardiac function with a left ventricular ejection fraction \>50%;
8. Acceptable respiratory function (FEV1\>1.5L, DLCO\>50%) and ability to tolerate radical lung cancer surgery;
9. 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;
10. Acceptable renal function with a glomerular filtration rate ≥ 60 mL/min;
11. Acceptable liver function with total bilirubin ≤ 1.5 x ULN, AST ≤ 3 x ULN, and ALT ≤ 3 x ULN;
12. Presence of measurable lesions as defined by RECIST 1.1 criteria;
13. 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:

1. Pathological histologically confirmed small cell lung cancer, squamous epithelial cell carcinoma and other pathological subtypes cannot be enrolled;
2. 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;
3. Patients with a history of active autoimmune disease or autoimmune disease that is likely to recur cannot be enrolled;
4. 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;
5. Patients who are allergic to chemotherapeutic agents such as carboplatin, paclitaxel, albumin paclitaxel, pemetrexed;
6. Patients with a history of allergy to monoclonal antibody drugs;
7. Patients who have previously received an allogeneic stem cell transplant or organ transplant；
8. Patients with mental illness or any other illness that makes it impossible to comply with treatment；
9. Patients who are unable or unwilling to sign the informed consent form；
10. 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.

Primary outcomes:
measure: Pathologic Complete Response (pCR) Rate
timeFrame: Within 1 week after surgery
Secondary outcomes:
measure: Major Pathologic Response (MPR) Rate
timeFrame: Within 1 week after surgery
measure: Pathologic Complete Response (pCR) Rate in non-squamous NSCLC with different EGFR mutations status
timeFrame: Within 1 week after surgery
measure: Major Pathologic Response (MPR) Rate in non-squamous NSCLC with different EGFR mutations status
timeFrame: Within 1 week after surgery
measure: Pathologic Complete Response (pCR) Rate in non-squamous NSCLC with different PD-L1 expression levels
timeFrame: Within 1 week after surgery
measure: Major Pathologic Response (MPR) Rate in non-squamous NSCLC with different PD-L1 expression levels
timeFrame: Within 1 week after surgery
measure: Event-free Survival (EFS)
timeFrame: Up to 24 months after participation
measure: The Safety and Tolerability
timeFrame: Up to 24 months after participation
Other outcomes:
Locations:
Study officials:
affiliation: Peking University People's Hospital
name: Fan Yanf, M.D.
role: STUDY_CHAIR
References: