Using Toripalimab before surgery for advanced lung cancer with specific mutations

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

This study is testing if giving a new immunotherapy called Toripalimab before surgery can help people with advanced lung cancer who have specific genetic mutations feel better and improve their chances of recovery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ruijin Hospital (Academic / other)
• Drugs / interventions: chemotherapy, Toripalimab, immunotherapy
• Locations: 2 sites (Guangzhou, Guangdong and 1 other locations)
• Trial ID: NCT06269211 on ClinicalTrials.gov

What this trial studies

This clinical trial is a Phase II, open-label, multicenter study that investigates the use of neoadjuvant Toripalimab in patients with clinically stage II-IIIB resectable non-small cell lung cancer (NSCLC) who have EGFR mutations and PD-L1 positive expression. The trial aims to improve the prognosis of these patients by exploring the effectiveness of immunotherapy before surgical intervention. Participants will be closely monitored for their response to the treatment, and the study will provide insights for future clinical trials involving similar therapies in this patient population.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with resectable stage II-IIIB NSCLC, confirmed EGFR mutations, and PD-L1 expression of 1% or higher.

Not a fit: Patients with squamous cell lung cancer or those who have received prior systemic treatment for NSCLC may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly enhance treatment outcomes for patients with advanced lung cancer who have specific genetic markers.

How similar studies have performed: Other studies have shown promising results with neoadjuvant immunotherapy in lung cancer, suggesting that this approach may be beneficial, although this specific combination is still being explored.

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.

Where this trial is running

Guangzhou, Guangdong and 1 other locations

• Guangdong Provincial People's Hospital — Guangzhou, Guangdong, China (Recruiting)
• Ruijin Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Hecheng Li, PhD, MD — Ruijin hospitalRuijin Hospital, Shanghai Jiao Tong University School of Medicine
• Study coordinator: Hecheng Li, PhD, MD

Conditions Carcinoma, Non-Small-Cell Lung