Clinical trial NCT06269211: Neoadjuvant Toripalimab for Clinically Stage II-IIIB Resectable Non-small Cell Lung Cancer with EGFR Mutation and PD-L1 Positive Expression
Official title: Neoadjuvant Toripalimab for Clinically Stage II-IIIB Resectable Non-small Cell Lung Cancer with EGFR Mutation and PD-L1 Positive Expression: a Prospective, Open-label, Multicenter, Single-arm Phase II Clinical Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: Guangdong Provincial People's Hospital
First posted: 2024-02-21
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study has only one arm, neoadjuvant Toripalimab treatment arm. Primary endpoint is MPR. We apply the optimal design of Simon's two-stage model to calculate the sample size and set both sides α= 0.05 and power=0.8, resulting in a total sample size of 29. Among them, 10 patients will be enrolled in the first stage. If the number of MPR cases in the first stage is less than or equal to 1, the study will be terminated in the early stage; On the contrary, participants in the second stage will continue to be enrolled. If the total number of MPR cases is greater than or equal to 5 after the completion of the second stage, the study is considered positive.
Primary purpose: TREATMENT

Brief summary: The study is a prospective, open label, multicenter, single arm Phase II clinical trial, aiming to explore the use of neoadjuvant Toripalimab for clinically stage II-IIIB NSCLC patients with EGFR mutations and PD-L1 positive expression, providing a novel perspective for further improving the prognosis of NSCLC patients. This study will provide valuable information for further clinical trials of neoadjuvant Toripalimab and other immune checkpoint inhibitors in NSCLC patients with EGFR mutations and PD-L1 positive expression.

Detailed description: For resectable locally advanced non-small cell lung cancer (NSCLC), the combination of neoadjuvant therapy and surgery has benefited the patients and has become a clinical routine and guideline recommended treatment. Among the East Asian NSCLC population, about 30% are positive for EGFR driver gene mutations. The efficacy of this population receiving neoadjuvant chemotherapy and EGFR inhibitors is limited, and their optimal neoadjuvant treatment strategy is still unclear. The neoadjuvant immunotherapy has achieved good therapeutic effects in driver-negative NSCLC patients, and is superior in PD-L1 expression positive patients.

Based on the above evidence, the investigators plan to conduct a prospective, open label, multicenter, single arm Phase II clinical study to explore the use of neoadjuvant Toripalimab for clinically stage II-IIIB NSCLC patients with EGFR mutations and PD-L1 positive expression, providing a novel perspective for further improving the prognosis of NSCLC patients.

Eligibility criteria: Inclusion Criteria:

1. Men and women aged ≥ 18 years old.
2. Baseline tumor tissues have to be obtained through biopsy (percutaneous or transbronchial) or surgery at study center.
3. Histologically confirmed diagnosis of primary non-small lung cancer on non-squamous histology.
4. Pre-treatment stage as clinical II-IIIB (AJCC/UICC 8th Edition) (stage IIIB excludes N3 disease); curative resectability has to be explicitly verified by the experienced surgical investigator.
5. Confirmation by the central laboratory that the tumor harbors EGFR mutations either sensitive mutations, uncommon mutations or complex mutations.
6. Have a PD-L1 tumor proportion score (TPS) ≥ 1% determined by IHC at the central laboratory. In order to balance patients with high PD-L1 expression (≥50%) and low PD-L1 expression (1-49%), we planned to enroll PD-L1 high and low patients at a ratio of 1:1.
7. Have not received prior systemic treatment for NSCLC.
8. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
9. Expected survival ≥ 3 months.
10. Adequate blood and organ function.

Exclusion Criteria:

1. Patients with histologically confirmed squamous cell carcinoma, combined small cell carcinoma and large cell carcinoma.
2. Molecular testing confirmed ALK translocation.
3. Treatment with prior systemic cancer therapy for the current lung cancer at any time (chemotherapy, radiotherapy, target therapy, ablation, and any other local or systemic therapy).
4. Patients with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colorectal, endometrial, cervical, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period.
5. Any active or history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications. Subjects with vitiligo, type I diabetes mellitus, resolved childhood asthma/atopy, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement or unexpected conditions of recurrence in the absence of an external trigger are allowed to be included.
6. Subjects with a history of interstitial lung disease, pneumonitis, or poorly controlled lung disease (including pulmonary fibrosis, acute lung diseases).
7. Severe chronic or active infections that require systemic antimicrobial, antifungal, or antiviral treatment, including tuberculosis infections.
8. Patients with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with HBV DNA ≥ 500 IU/mL \[2500 copies/mL\] should be excluded.
9. Has known active hepatitis C virus (HCV). Active HCV is defined by positive tests for HCV Ab and quantitative HCV RNA.
10. Known positive history or positive test for Human Immunodeficiency Virus (HIV).
11. The investigator believes that there is a high risk of bleeding (such as esophageal varices with bleeding risk, local active ulcer lesions) or active hemoptysis.
12. History of allergy to study drug components.
13. Pregnant and lactating women are excluded.
14. Fertile men or their female partners (women of childbearing potential, WOCBP) who are not willing to use contraception.
15. Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or understand the patient information.
16. The investigator believes that there are factors that can increase medication risk or confuse outcome judgment.

Primary outcomes:
measure: Major Pathological Response (MPR)
timeFrame: MPR will be assessed within 2 weeks after surgery
Secondary outcomes:
measure: Pathological Complete Response (pCR)
timeFrame: pCR will be assessed within 2 weeks after surgery
measure: Objective Response Rate (ORR)
timeFrame: Tumor response will be evaluated within 30 days after last dose of neoadjuvant treatment
measure: 2-year Event Free Survival (EFS)
timeFrame: 2 years after the date of initiation of neoadjuvant treatment
measure: 2-year Overall Survival (OS)
timeFrame: 2 years after the date of initiation of neoadjuvant treatment
measure: Safety (Number of Participants With Grade 3 and Higher-grade Treatment-related Adverse Events)
timeFrame: From date of neoadjuvant treatment until surgery was applied during study period or up to at least 90 days after last dose.
measure: Feasibility (Number of Participants Who Finished Neoadjuvant therapy and Receive Surgery Within 3-6 Weeks After Neoadjuvant Therapies)
timeFrame: 6 weeks after last dose of neoadjuvant treatment
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: Ruijin hospitalRuijin Hospital, Shanghai Jiao Tong University School of Medicine
name: Hecheng Li, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: