NSCLC
Conditions
Brief summary
This is a single-center, single-arm, phase 2 trial evaluating the efficacy and safety of retlirafusp alfa combined with single-agent chemotherapy as neoadjuvant treatment for patients with resectable stage II-III EGFR/ALK wild-type non-small cell lung cancer (NSCLC).Eligible patients receive 4 cycles of neoadjuvant therapy, followed by curative surgery and 1-year maintenance therapy with retlirafusp alfa.Primary endpoints are pathological complete response (pCR) rate and safety. Secondary endpoints include major pathological response (MPR), event-free survival (EFS), and overall survival (OS).
Interventions
DRUGDrug: Retlirafusp alfa
30mg/kg intravenously every 3 weeks (Q3W) for neoadjuvant and maintenance therapy
DRUGDrug: Single-agent Chemotherapy
Nab-paclitaxel or pemetrexed (per histology), intravenously Q3W
OTHERProcedure: Radical Surgery
Radical resection of lung cancer after neoadjuvant therapy
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-75 years * ECOG Performance Status 0-1; * Treatment-naive patients with histologically or cytologically confirmed NSCLC (via biopsy) and radiologically confirmed Stage II-III disease; * Patients with adenocarcinoma must be confirmed to be free of driver gene mutations such as EGFR or ALK; patients with squamous cell carcinoma do not require genetic testing; * Patients must have measurable lesions; * Patients whose disease was assessed as CR, PR, or SD following 2 cycles of neoadjuvant chemotherapy with Rilpufan α in combination with a single-agent non-platinum chemotherapy; * Life expectancy of at least 12 weeks; * Good function of other major organs (liver, kidneys, hematopoietic system, etc.): - Hemoglobin ≥ 9.0 g/dL (this level may be maintained or exceeded through blood transfusion); - Red blood cell count ≥ 2.0 × 10⁹/L; - Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L; - Platelet count ≥ 100 × 10⁹/L; - Total bilirubin within normal limits; - Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase ≤ 2.5 times the upper limit of normal; - Creatinine ≤ 2.0 mg/dL; and creatinine clearance ≥ 60 mL/min; - For patients who have not received anticoagulant therapy: International Normalized Ratio (INR) for prothrombin time ≤ 1.5, and activated partial thromboplastin time (APTT) ≤ 1.5 times the upper limit of normal. Patients receiving full-dose or parenteral anticoagulant therapy may be enrolled in the clinical trial provided that the anticoagulant dose has been stable for at least 2 weeks prior to study entry and the results of coagulation tests fall within the limits established by the local treatment center. * No systemic metastases; * Expected to be completely resectable; * Good pulmonary function sufficient to tolerate surgical treatment; * Women of childbearing potential must undergo a pregnancy test within 7 days prior to the start of treatment and receive a negative result; * Participants must use reliable contraception (e.g., intrauterine device, oral contraceptives, and condoms) during the trial and for 30 days after its completion; 14 Participants voluntarily enroll in the study, sign an informed consent form, demonstrate good compliance, and cooperate with follow-up.
Exclusion criteria
* Any systemic anticancer therapy for NSCLC, other than neoadjuvant therapy as specified in the inclusion criteria, including surgery, local radiotherapy, cytotoxic drug therapy, targeted drug therapy, and experimental treatments; * Patients who have had a cancer other than NSCLC within five years prior to the start of this trial; * Patients with unstable systemic diseases, such as uncontrolled hypertension or severe arrhythmias; * Patients with active, known, or suspected autoimmune diseases; * Patients with a history of or current interstitial lung disease; * Patients with HIV infection; * Patients who have undergone major systemic surgery or suffered severe trauma within 2 months prior to the start of this trial; * Pregnant or breastfeeding women; * Patients with neurological or psychiatric disorders who are unable to comply with the study protocol; * Other circumstances deemed unsuitable for enrollment by the investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological Complete Response (pCR) Rate | Assessed at the time of surgery, approximately 6-8 weeks after completion of neoadjuvant therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathological Response (MPR) Rate | Assessed at the time of surgery. | — |
| Event-Free Survival (EFS) | Assessed from randomization up to 36 months post-surgery. | — |
| Overall Survival (OS) | From the start of randomization until the study end date (expected January 30, 2028) | The time from randomization to death from any cause. |
| Pathological Response (PR) Rate | Assessed at the time of surgery. | — |
| R0 resection rate | Assessment within 24 hours after surgery | The percentage of patients with no residual tumor at the surgical margin. |
| Changes in EORTC QLQ-C30 Scores | Baseline; before each cycle of neoadjuvant therapy; at the time of surgery; 3, 6, and 12 months post-surgery | Patients completed the EORTC QLQ-C30 questionnaire to assess changes from baseline in scores across the functional domains (physical, role, emotional, cognitive, and social) and the symptom domain. The total score on the questionnaire is 100; higher scores in the functional domains indicate better quality of life, while higher scores in the symptom domain indicate more severe symptoms. |
| Recurrence-Free Survival (RFS) | Assessed from surgery up to 5 years post-surgery. | — |
| Number of positive lymph nodes | Assessment will be conducted after the surgery, once the pathology report is available. | The total number of lymph nodes that tested positive on pathological examination in the surgical specimen. |
| Incidence of severe postoperative complications (Clavien-Dindo classification ≥ Grade III) | Continuous monitoring from the time of surgery through 30 days postoperatively. | The proportion of patients who experienced severe complications classified as Clavien-Dindo grade ≥III within 30 days postoperatively. |
| Incidence and severity of adverse events (CTCAE v6.0) | The period is calculated from the first administration of the study drug until 30 days after the last dose; for delayed adverse reactions, the period is calculated until 1 year after the last dose. | In accordance with the CTCAE v6.0 criteria, assess the incidence and severity grading of all adverse events occurring during treatment. |
| Percentage of patients whose dosage was adjusted due to adverse events | Calculated from the start of the first treatment with the study drug until 30 days after the last dose. | The proportion of patients who required dose reduction or treatment interruption due to adverse events out of the total number of enrolled patients. |
| Changes in EORTC QLQ-LC13 Scores | Baseline; before each cycle of neoadjuvant therapy; at the time of surgery; 3, 6, and 12 months post-surgery. | Patients completed the EORTC QLQ-LC13 questionnaire to assess changes in scores for lung cancer-related symptoms (such as cough, shortness of breath, and pain) compared to baseline. The scale is scored out of 100, with higher scores indicating more severe symptoms. |
Contacts
CONTACTZhenfa Zhang Zhenfa Zhang
Outcome results
None listed