Adjuvant Benmelstobart for Stage IB, Grade 3 Invasive Lung Adenocarcinoma

This study is a prospective, single-arm, phase 2 clinical trial assessing the feasibility, efficacy, and safety of the PD-L1 inhibitor Benmelstobart (TQB2450) as an adjuvant therapy regimen in patients with pathologic stage IB, IASLC grade 3 invasive lung adenocarcinoma without EGFR active mutations or ALK rearrangement.

The target population for this study includes patients with pathologic stage IB, IASLC grade 3 invasive lung adenocarcinoma without EGFR active mutations or ALK rearrangement who have undergone radical resection at Shanghai Pulmonary Hospital. Patients are screened and enrolled within 4 to 12 weeks after surgery. Following surgery, adjuvant chemotherapy may be administered based on the patient's treatment needs or the attending physician's assessment. Subsequently, patients will receive adjuvant immunotherapy with the PD-L1 inhibitor Benmelstobart (TQB2450 injection) at a dose of 1200 mg every 3 weeks by intravenous injection, for a maximum of 16 cycles. The primary endpoint is the 2-year disease-free survival (DFS) rate. The secondary endpoints include the 3-year and 5-year DFS rates, the 5-year overall survival (OS) rate, and drug safety. The sample size is 62 patients.

Eligibility Criteria:
Inclusion Criteria:

1. Participants are able to understand the informed consent form, voluntarily agree to participate, and sign the informed consent form;
2. Participants must be 18 years or older and under 75 years of age on the day they sign the informed consent form;
3. Pathologically confirmed stage IB (AJCC TNM staging, 8th edition) lung adenocarcinoma;
4. Achieved complete resection (R0) after lobectomy, bilobectomy, or sleeve resection;
5. Pathologically diagnosed as grade 3 invasive lung adenocarcinoma according to the 2020 grading system proposed by the International Association for the Study of Lung Cancer (IASLC) Pathology Committee (poorly differentiated: any tumor with 20% or more of high-grade patterns, including solid, micropapillary, and/or complex glandular patterns);
6. No prior receipt of any anti-tumor treatment, including but not limited to systemic chemotherapy, immunotherapy, or radiotherapy;
7. Expected survival time more than 12 weeks;
8. No active EGFR mutations (including but not limited to exon 19 deletions, exon 21 L858R, exon 21 L861Q, exon 18 G719X, or exon 20 S768I mutations) or ALK rearrangements;
9. Tumor PD-L1 expression ≥1% (the PD-L1 IHC 22C3 pharmDx reagent, antibody clone number: 22C3, detection platform: DAKO Autostainer Link 48);
10. Patients are screened and enrolled within 4 to 12 weeks after surgery;
11. Performance status score of 0 or 1 (Eastern Cooperative Oncology Group (ECOG) performance status scale);
12. For female participants of childbearing potential, a negative serum pregnancy test must be obtained within 7 days prior to the first dose of the study drug;
13. Female participants of childbearing potential or male participants with partners of childbearing potential must agree to use highly effective contraception (with an annual failure rate of less than 1%) starting from 7 days before the first dose of the study drug and continuing until 24 weeks after the last dose;
14. Major organ functions must be normal within 7 days prior to the first dose of the study drug.

Exclusion Criteria:

1. Postoperative pathological diagnosis of mixed histological features;
2. Incomplete resection (R1/R2) or wedge resection, segmentectomy;
3. Currently participating in an interventional clinical trial, or having received other investigational drugs or used investigational devices within 4 weeks prior to the first dose of the study drug;
4. Systemic corticosteroids or immunosuppressants must have been administered continuously for 7 days within 14 days prior to the first dose of the study drug;
5. Received live vaccines (including attenuated live vaccines) within 28 days prior to the study drug administration;
6. History of or currently having interstitial lung disease/condition requiring systemic corticosteroid treatment;
7. History of or currently having autoimmune disease;
8. Presence of other malignant tumors within 5 years prior to the first dose of the study drug;
9. Presence of uncontrolled comorbidities such as cardiac, renal, gastrointestinal, or infectious diseases;
10. History of allogeneic bone marrow or organ transplantation;
11. History of using any antibodies or drugs targeting T-cell co-regulatory proteins (immune checkpoints), or previous treatment with anti-tumor vaccines;
12. History of hypersensitivity or intolerance to antibody-based drugs, history of any rapid allergic reactions, uncontrolled asthma, or significant drug allergies;
13. Pregnant and/or breastfeeding women;
14. Other conditions that may affect the safety or compliance of the study drug, including but not limited to psychiatric disorders, uncontrolled large pleural effusions, or moderate to large pleural effusions requiring repeated drainage.