Short-course radiation then tislelizumab plus anlotinib before and after surgery for stage II–IIIA lung cancer

Prospective Phase II Study of Hypofractionated Radiotherapy Sequential Tislelizumab and Anlotinib in the Neoadjuvant and Adjuvant Therapy for Stage II-IIIA Non-Small Cell Lung Cancer

This study will try short-course radiotherapy followed by the immune drug tislelizumab and the targeted drug anlotinib given before and after surgery for people with stage II–IIIA non-small cell lung cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Zhejiang Cancer Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, tislelizumab, anlotinib
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06379087 on ClinicalTrials.gov

What this trial studies

This is a single-center, prospective, single-arm Phase 2 study testing hypofractionated radiotherapy (24 Gy in 3 fractions) followed within one week by two neoadjuvant 3-week cycles of tislelizumab plus anlotinib. Patients who proceed to surgery will then receive adjuvant tislelizumab and anlotinib every 3 weeks for up to one year. The trial will measure 1-year event-free survival and pathological endpoints including complete pathological response (pCR) and major pathological response (MPR), along with safety and tolerability. All participants must have resectable stage II–IIIA NSCLC without common driver mutations and meet baseline performance and organ-function requirements.

Who should consider this trial

Good fit: Adults aged 18–75 with resectable stage II–IIIA non-small cell lung cancer, negative for EGFR/ALK/ROS1 driver mutations, ECOG 0–1, at least one measurable lesion, and eligible for hypofractionated radiotherapy are the intended participants.

Not a fit: Patients with unresectable disease, positive EGFR/ALK/ROS1 driver mutations, poor performance status, or those who cannot tolerate immunotherapy, anti-angiogenic therapy, or radiotherapy are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, this approach could shrink tumors before surgery and reduce recurrence after surgery, potentially increasing the chance of long-term, event-free survival.

How similar studies have performed: Neoadjuvant PD-1/PD-L1 therapies have shown promising pCR/MPR rates in other trials, but the specific sequence combining hypofractionated radiotherapy with tislelizumab plus anlotinib remains relatively novel and less well established.

Eligibility criteria

Inclusion Criteria:

* (1) Aged 18-75 years old;
* (2) Early stage II-IIIA NSCLC (AJCC 8th edition), NSCLC, confirmed in tissue (AJCC eighth edition);
* (3) All lesions are assessed to be eligible for surgical resection;
* (4) The primary tumor can be treated with hypofractionated radiotherapy after evaluation;
* (5) Epidermal growth factor receptor/anaplastic lymphoma kinase/ROS1 gene fusions mutation was negative in primary tumor or lymph node metastasis;
* (6) ECOG PS score: 0\~1;
* (7) Expected survival more than 1 year;
* (8) At least one measurable lesion (RECIST 1.1);
* (9) Females of childbearing potential should agree to use contraceptive measures (such as intrauterine device, contraceptives or condoms) during the study and within 3 months after the end of the study; have a negative serum or urine pregnancy test within 7 days before study enrollment and must be non-lactating subjects; and males should agree to use contraceptive measures during the study and within 3 months after the end of the study period;
* (10) Subjects voluntarily participate in this study, sign the informed consent form and had good compliance;
* (11) Subjects are suitable after MDT discussion.

Exclusion Criteria:

Participants with any of the following criteria were excluded from the trial:

* (1) The location of the primary tumor was assessed by the radiologist and considered unsuitable for hypofractionated therapy;
* (2) The pathological type is small cell lung cancer, or mixed tumor with small cell components;
* (3) A history of or concurrent with other malignancies;
* (4) Received any anti-tumor treatment before this study, including chemotherapy, radiotherapy, targeted therapy (including but not limited to monoclonal antibodies, small molecule tyrosine kinase inhibitors, etc.) and immunotherapy;
* (5) The Imaging (CT/MR/PET-CT) showed tumor invasion of great vessels or blurred boundary with blood vessels, or the presence of any pulmonary cavity or necrotic lesions;
* (6) Hemoptysis, active bleeding, ulcer, intestinal perforation, intestinal obstruction within 3 months before enrollment;
* (7) Previous interstitial lung disease, drug-induced interstitial disease or any clinical evidence of active interstitial lung disease; baseline CT scan found idiopathic pulmonary fibrosis;
* (8) According to the investigator's judgment, there are serious or uncontrollable systemic diseases (such as unstable or uncompensated respiratory, cardiac, hepatic or renal diseases) or any unstable systemic diseases (including active infection, grade III hypertension, unstable angina, congestive heart failure, liver and kidney or metabolic diseases);
* (9) Previous treatment with anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or drugs acting on another co-inhibitory T cell receptor (e.g., CTLA-4, OX-40, CD137);
* (10) The presence of uncontrollable third space effusion, such as a large number of pleural effusion or ascites or pericardial effusion;
* (11) Urine routine showed urine protein ≥ + +, or 24h urine protein ≥ 1g or severe liver and kidney dysfunction;
* (12) Uncontrollable hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg);
* (13) Subjects requiring systemic treatment with corticosteroids (\> 10 mg/day prednisone or equivalent) or other immunosuppressive agents within 14 days before the first dose;
* (14) Hyperactive/venous thrombotic events occurred within 6 months, such as cerebrovascular accident (including cerebral hemorrhage, cerebral infarction, temporary ischemic attack, etc.);
* (15) Excessive surgery or significant trauma within 28 days before enrollment;
* (16) Pregnant or lactating women;
* (17) Subjects who are considered to be unsuitable for enrollment for other reasons according to the judgment of the investigators..

Where this trial is running

Hangzhou, Zhejiang

• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Min Fang, PhD

Conditions Non-Small Cell Lung Cancer