Relatrilfa-α Plus Single-Agent Chemotherapy as Neoadjuvant Therapy for Resectable Stage II-III NSCLC (Phase 2)

Phase 2Not Yet RecruitingNCT07550920

Tianjin Medical University Cancer Institute and Hospital18 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

NSCLC

Interventions

Drug: Retlirafusp alfa

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Pathological Complete Response (pCR) Rate

Time frame: Assessed at the time of surgery, approximately 6-8 weeks after completion of neoadjuvant therapy.

Secondary Outcomes

Major Pathological Response (MPR) Rate

Time frame: Assessed at the time of surgery.

Event-Free Survival (EFS)

Time frame: Assessed from randomization up to 36 months post-surgery.

Overall Survival (OS)

The time from randomization to death from any cause.

Time frame: From the start of randomization until the study end date (expected January 30, 2028)

Pathological Response (PR) Rate

Time frame: Assessed at the time of surgery.

R0 resection rate

The percentage of patients with no residual tumor at the surgical margin.

Time frame: Assessment within 24 hours after surgery

Changes in EORTC QLQ-C30 Scores

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.

Time frame: Baseline; before each cycle of neoadjuvant therapy; at the time of surgery; 3, 6, and 12 months post-surgery

Recurrence-Free Survival (RFS)

Time frame: Assessed from surgery up to 5 years post-surgery.

Number of positive lymph nodes

The total number of lymph nodes that tested positive on pathological examination in the surgical specimen.

Time frame: Assessment will be conducted after the surgery, once the pathology report is available.

Incidence of severe postoperative complications (Clavien-Dindo classification ≥ Grade III)

The proportion of patients who experienced severe complications classified as Clavien-Dindo grade ≥III within 30 days postoperatively.

Time frame: Continuous monitoring from the time of surgery through 30 days postoperatively.

Incidence and severity of adverse events (CTCAE v6.0)

In accordance with the CTCAE v6.0 criteria, assess the incidence and severity grading of all adverse events occurring during treatment.

Time frame: 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.

Percentage of patients whose dosage was adjusted due to adverse events

The proportion of patients who required dose reduction or treatment interruption due to adverse events out of the total number of enrolled patients.

Time frame: Calculated from the start of the first treatment with the study drug until 30 days after the last dose.

Changes in EORTC QLQ-LC13 Scores

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.

Time frame: Baseline; before each cycle of neoadjuvant therapy; at the time of surgery; 3, 6, and 12 months post-surgery.