Neoadjuvant immunotherapy for localized non-small cell lung cancer with rare mutations

Neoadjuvant Toripalimab Combined With Chemotherapy in Rare Mutations Stage IIB-IIIB NSCLC

This study is testing if a combination of a new immunotherapy drug and chemotherapy can help people with localized lung cancer that has rare mutations by seeing if it can completely eliminate the tumor.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Guangdong Provincial People's Hospital (Academic / other)
• Drugs / interventions: Toripalimab, chemotherapy, radiation
• Locations: 1 site (Guanzhou, Guangdong)
• Trial ID: NCT05800340 on ClinicalTrials.gov

What this trial studies

This Phase II, single-arm, open-label study evaluates the clinical feasibility and safety of administering three cycles of Toripalimab combined with chemotherapy in patients with localized non-small cell lung cancer (NSCLC) harboring rare mutations. A total of 30 eligible patients will receive treatment, and dynamic blood samples will be collected for exploratory analysis. The primary goal is to achieve a pathological complete response, defined as no residual tumor in the primary lung cancer and metastatic lymph nodes. Following treatment, patients may receive optional adjuvant therapy based on the investigators' discretion.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with Stage IIB-IIIB NSCLC and specific rare driver mutations.

Not a fit: Patients with Stage I or Stage IV NSCLC or those who have previously received anti-tumor drugs or radiotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with rare mutations in NSCLC.

How similar studies have performed: While there have been studies on immunotherapy in NSCLC, this specific approach targeting rare mutations is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Age: 18 Years and older
2. ECOG physical score 0-1 points; expected survival time ≥ 3 months;
3. Pathologically confirmed diagnosis with Stage IIB-IIIB NSCLC which harbored rare driver alteration including RET fusions, BRAF (V600E or non-V600E but confirmed driver mutations), ERBB2 exon20 insertion, MET amplification (FISH confirmed) or exon 14 skipping. Suspected N2 disease should be confirmed by either mediastinoscopy or EBUS. N1 disease could be determined through PET/CT but biopsy of primary lung cancer is needed;
4. Lung function capacity capable of tolerating the proposed lung surgery
5. Available tissue of tumor for PD-L1 test
6. Subjects voluntarily joined the study and signed informed consent, with good compliance to follow-up.

Exclusion Criteria:

1. Stage I and stage IV NSCLC;
2. Patients who have previously used any other anti-tumor drugs or radiotherapy;
3. Large panel NGS indicated sensitive EGFR alteration, ALK fusion, ROS1 fusion or any other driver mutations combined with MDM2/MDM4 amplification;
4. Histologically confirmed small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer);
5. A history of active bleeding within the 6 months before enrollment, or receiving thrombolysis or anticoagulant therapy, or the investigator believes that there is a clear tendency to gastrointestinal bleeding (such as esophageal varices with bleeding risk, local activity) Ulcer lesions, etc.) or active hemoptysis;
6. Patients with any underlying disease that investigators consider it may affect patient's prognosis including sever cardiovascular, pulmonary disease or serious infections; Clinically obvious gastrointestinal abnormalities, which may affect the intake, transport or absorption of drugs (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.), or patients with total gastrectomy;
7. Known or suspected autoimmune disease with activity. Participants may be enrolled if they have type 1 diabetes, hypothyroidism that requires only hormone replacement therapy, skin diseases that require no systemic treatment (such as purpura, psoriasis, or hair loss), or other conditions that are not expected to return without external trigger.
8. Patients with active hepatitis B (positive for HBsAg) or hepatitis C (positive for HCV RNA).
9. Patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
10. Patients with other active malignancies within five years
11. Pregnant or lactating women; those who have fertility are unwilling or unable to take effective contraceptive measures;
12. Patients with low compliance or willingness to take the drugs and surveillance.

Where this trial is running

Guanzhou, Guangdong

• Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences — Guanzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Wen-Zhao Zhong, Ph.D

Conditions Non-Small Cell Lung Cancer; RET Driver Mutation; BRAF V600 Mutation; Erb-B2 Receptor Tyrosine Kinase Exon 20 Mutation; MET Amplification; MET Exon 14 Skipping Mutation; Non-small Cell Lung Cancer; Neoadjuvant immunotherapy