Adjuvant L-TIL plus tislelizumab after surgery for resectable NSCLC without pCR

A Prospective Phase II Clinical Trial Evaluating Liquid Tumor-infiltrating Lymphocytes (L-TIL) in Combination With Tislelizumab as Adjuvant Therapy in Patients With Resectable Stage II to IIIB (N2) Non-small Cell Lung Cancer (NSCLC) Who Have Undergone Surgery Following Neoadjuvant Treatment With an Immune Checkpoint Inhibitor Plus Platinum-based Doublet Chemotherapy and Did Not Achieve a Pathological Complete Response (pCR)

This trial tests whether giving liquid tumor-infiltrating lymphocytes (L-TIL) together with the PD-1 blocker tislelizumab after surgery helps people with resectable stage II–IIIB NSCLC who did not achieve a complete response to pre-surgery chemoimmunotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 41 (estimated)
• Ages: 17 Years to 75 Years
• Sex: All
• Sponsor: Tianjin Medical University Cancer Institute and Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, tislelizumab
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT07330037 on ClinicalTrials.gov

What this trial studies

This is a Phase II, single-center trial of adjuvant cellular therapy (L-TIL) combined with tislelizumab in patients with resectable stage II–IIIB non-small cell lung cancer who had neoadjuvant chemoimmunotherapy followed by R0 resection but did not achieve a pathological complete response. Eligible patients must be EGFR/ALK/ROS1-negative with ECOG 0–1 and adequate organ function. Participants will receive injections of expanded L-TIL cells alongside scheduled doses of tislelizumab and will be followed for safety and preliminary anti-tumor activity. The trial aims to determine whether this combination can reduce recurrence risk and is tolerable in the post-surgery adjuvant setting.

Who should consider this trial

Good fit: Ideal candidates are adults with resectable stage II–IIIB (including N2) NSCLC who are EGFR/ALK/ROS1-negative, had 2–4 cycles of neoadjuvant chemoimmunotherapy followed by R0 resection without pCR, and have ECOG 0–1 with adequate organ function.

Not a fit: Patients with targetable driver mutations, a pathological complete response after neoadjuvant therapy, poor performance status, significant organ dysfunction, or unresectable disease are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could lower recurrence risk after surgery and improve long-term outcomes by boosting anti-tumor immune activity.

How similar studies have performed: Adoptive TIL therapies have produced strong and durable responses in melanoma and early signals in several solid tumors, but combining L-TIL with PD-1 blockade as adjuvant therapy in resectable NSCLC is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Histologically or cytologically confirmed NSCLC with imaging indicating resectable stage II-IIIB (N2) disease according to the ninth edition of the AJCC lung cancer TNM staging system;
* No prior anti-tumor treatment;
* Negative for EGFR/ALK/ROS1 mutations;
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
* Undergone 2-4 cycles of neoadjuvant therapy combining immunotherapy and chemotherapy, followed by surgical resection with R0 margins but without achieving a complete pathological response (non-pCR);
* Adequate organ function as defined below (without using any blood products or hematopoietic growth factors within 14 days):

Normal bone marrow reserve: neutrophil count ≥1.5×10⁹/L, lymphocyte count ≥0.6×10⁹/L, platelet count ≥100×10⁹/L, hemoglobin ≥90g/L; Normal renal function: serum creatinine ≤1.5 mg/dL and/or creatinine clearance rate ≥60 mL/min; Normal liver function: total bilirubin ≤1.5 times ULN, AST and ALT ≤1.5 times ULN; Normal coagulation function: APTT ≤1.5 times ULN, INR ≤1.5 times ULN, PT ≤1.5 times ULN; Left ventricular ejection fraction (LVEF) ≥50% on echocardiography; Pulmonary function test showing FEV1 ≥60%;

* For non-surgically sterilized or women of childbearing potential, must agree to use medically approved contraception (such as an intrauterine device, contraceptive pills, or condoms) during the study treatment period and for 3 months after the end of treatment; must have a negative serum or urine HCG test within 7 days prior to study entry; must not be breastfeeding;

Exclusion Criteria:

* Vaccination within 28 days prior to the first dose, except for inactivated vaccines;
* Major surgery within 28 days prior to the first dose;
* History of other malignancies within 5 years prior to screening;
* Congenital or acquired immunodeficiency, such as HIV infection, or active hepatitis (for inclusion criteria, ALT and AST levels must be within specified limits; for hepatitis B: HBV DNA \>10\^4/ml; for hepatitis C: HCV RNA \>10\^3/ml; for chronic hepatitis B carriers, HBV DNA \>2000 IU/ml (\>10\^4 copies/ml), antiviral treatment must be concurrently administered during the study period);
* Unstable or severe concurrent diseases within 6 months prior to the first dose, such as severe/unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction, pulmonary hypertension, life-threatening ventricular arrhythmias requiring maintenance therapy, stroke, and uncontrolled severe seizures;
* Clinically significant active pneumonia or other respiratory system diseases severely affecting lung function at screening;
* Active autoimmune diseases, history of autoimmune diseases, or conditions requiring systemic corticosteroids or immunosuppressive drugs;
* Arterial or venous thrombotic events occurring within 6 months prior to screening;
* History or CT findings indicating active tuberculosis within 1 year prior to enrollment that was untreated;
* Active infections requiring systemic anti-infective treatment;
* Active gastrointestinal bleeding or contraindications to IL-2 use;
* Previous bone marrow transplant or solid organ transplant;
* Other serious acute or chronic medical or psychiatric illnesses (including suicidal ideation or behavior within one year) that may increase the risk associated with participation in the study or administration of the investigational treatment, interfere with the investigational treatment and follow-up, or affect the subject's compliance;

Where this trial is running

Tianjin, Tianjin Municipality

• Tianjin Medical University Cancer Institute and Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Study coordinator: Dongsheng Yue, MD. Ph.D

Conditions NSCLC