Neoadjuvant Toripalimab for Non-squamous NSCLC With EGFR Mutation

NCT ID: NCT05962021

Last Updated: 2023-08-01

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 126 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-01
• Study Completion Date: 2026-06-30

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

19DEL cohort

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

Group Type: EXPERIMENTAL

Toripalimab plus Chemotherapy

Intervention Type: DRUG

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.

L858R cohort

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

Group Type: EXPERIMENTAL

Toripalimab plus Chemotherapy

Intervention Type: DRUG

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.

Interventions

Toripalimab plus Chemotherapy

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 17 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Junshi Bioscience Co., Ltd.

OTHER

Sponsor Role: collaborator

Peking University People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yang Fan, MD

Professor of Thoracic Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fan Yanf, M.D.

Role: STUDY_CHAIR

Peking University People's Hospital

Central Contacts

Fan Yang, M.D.

Role: CONTACT

yangfan@pkuph.edu.cn

+86-010-88326657

Xiang Yan, M.D.

Role: CONTACT

yxiang301@sina.com

+86-13581786750

Other Identifiers

JS001-ISS-CO413

Identifier Type: -

Identifier Source: org_study_id