Neoadjuvant BL-B01D1 plus Almonertinib for resectable EGFR‑positive stage II–IIIB lung cancer

A Phase II Study to Evaluate the Safety and Efficacy of Neoadjuvant Therapy With BL-B01D1 in Combination With Almonertinib Followed by Adjuvant Almonertinib in Patients With Epidermal Growth Factor Receptor Mutation Positive Stage II-IIIB Resectable Non-Small Cell Lung Cancer

This trial will test whether giving BL-B01D1 together with Almonertinib before surgery, followed by Almonertinib after surgery, helps adults with resectable EGFR‑positive stage II–IIIB non‑small cell lung cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sichuan University (Academic / other)
• Drugs / interventions: Almonertinib, radiation
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT06951464 on ClinicalTrials.gov

What this trial studies

This Phase II, open-label, single-arm trial gives investigational BL-B01D1 together with the EGFR inhibitor almonertinib before planned surgery, then continues almonertinib as adjuvant therapy. Participants are adults with EGFR‑sensitive mutation–positive stage II–IIIB NSCLC judged resectable and fit for lobectomy and systematic lymph node dissection. Researchers will monitor tumor response, surgical outcomes, safety, and recovery using standardized imaging and clinical assessments. The study is conducted at West China Hospital, Sichuan University, and requires on‑site treatment, surgery, and follow‑up at that center.

Who should consider this trial

Good fit: Adults aged 18–75 with EGFR‑sensitive mutation–positive stage II–IIIB NSCLC who are considered resectable, have ECOG ≤1, adequate pulmonary and organ function, and LVEF ≥50% are ideal candidates.

Not a fit: Patients with EGFR wild‑type or resistant mutations, unresectable disease, poor performance status, significant cardiac dysfunction, or inadequate organ function are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could shrink tumors before surgery, improve the likelihood of a complete resection, and lower the risk of recurrence.

How similar studies have performed: Neoadjuvant EGFR tyrosine kinase inhibitors have shown promise in shrinking EGFR‑mutant tumors prior to surgery, but combining almonertinib with the investigational BL-B01D1 is novel and has limited prior data.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily sign the informed consent form and comply with the study protocol requirements.
2. Male or female, Age ≥18 years and ≤75 years at the time of signing the informed consent form.
3. Diagnosed with stage II-IIIB (according to Version 8 of TNM staging) EGFR-sensitive mutation-positive non-small cell lung cancer (NSCLC) with feasibility or potential feasibility for radical surgery (radical lobectomy + systematic lymph node dissection), and assessed by the investigator as requiring neoadjuvant therapy.
4. Adequate pulmonary function to tolerate surgery.
5. Must have at least one measurable lesion per RECIST v1.1 criteria.
6. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤1.
7. No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50%.
8. Organ function levels must meet the following criteria:

   1. Bone marrow function: Absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelet count ≥100×10⁹/L, hemoglobin ≥90 g/L;
   2. Hepatic function: Total bilirubin (TBIL) ≤1.5×ULN, AST and ALT ≤2.5×ULN;
   3. Renal function: Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (Ccr) ≥50 mL/min (calculated by Cockcroft-Gault formula);
   4. Albumin ≥30 g/L.
9. Coagulation function: International normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5×ULN.
10. Urine protein: ≤2+ on dipstick or ≤1000 mg/24h.
11. Contraception: Females of childbearing potential or males with partners of childbearing potential must use highly effective contraception from 7 days before the first dose until 6 months after the last dose. Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose.

Exclusion Criteria:

1. Patients who have received previous systemic or local anti-tumor therapy for non-small-cell lung cancer.
2. Patients with other malignant tumors within 5 years before the first administration, except those who have been cured skin squamous cell carcinoma, basal cell carcinoma, superficial bladder cancer, prostate/cervix/breast cancer in situ and so on are considered to be eligible for enrollment.
3. Major surgery (investigator-defined) within 4 weeks before the first dose.
4. Current interstitial lung disease, drug-induced interstitial pneumonia, radiation pneumonitis requiring steroid therapy, or a history of these diseases.
5. Severe systemic infection occurred within 4 weeks before screening, including but not limited to severe pneumonia caused by fungi, bacteria, viruses, bacteremia, or serious infectious complications.
6. Patients at risk for active autoimmune disease, or with a history of autoimmune disease, Including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis, Wegener syndrome, autoimmune hepatitis, systemic sclerosis, Hashimoto's thyroiditis, autoimmune vasculitis, autoimmune neuropathy (Guillain-Barre syndrome), etc. Exceptions include type I diabetes mellitus, hypothyroidism that is stable with hormone-replacement therapy (including that due to autoimmune thyroiditis), psoriasis or vitiligo that does not require systemic treatment, and hypothyroidism that is stable with hormone-replacement therapy.
7. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBsAg positive or HBcAb positive and HBV-DNA copy number \> central detection lower limit) or hepatitis C virus infection (HCV antibody positive and HCV-RNA\> central detection lower limit).
8. Poorly controlled hypertension (systolic blood pressure \>150 mmHg or diastolic blood pressure \>100 mmHg).
9. A history of severe cardiovascular and cerebrovascular diseases, including but not limited to:

   1. severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, degree III atrioventricular block, complete left bundle branch block, frequent and uncontrollable arrhythmias, such as atrial fibrillation, atrial flutter, ventricular fibrillation, and ventricular flutter (except transient); h) prolonged QT interval (QTc\>450 msec in men or QTc\>470 msec in women) at rest (except transient);
   2. acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular or cerebrovascular event occurring within 6 months before the first dose;
   3. patients with New York Heart Association (NYHA) functional class ≥II heart failure;
   4. unstable angina pectoris;
   5. Patients with a history of cerebral infarction or cerebral hemorrhage within 6 months;
10. Previous history of allogeneic stem cell, bone marrow or organ transplantation.
11. Patients with a history of allergy to recombinant humanized antibodies or to BL-B01D1 or any excipients of Almonertinib Mesylate Tablets.
12. A history of autologous or allogeneic stem cell transplantation.
13. Pregnant or lactating women.
14. Other circumstances considered by the investigator to be inappropriate for participation in the trial.

Where this trial is running

Chengdu, Sichuan

• West China Hospital, Sichuan University — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Principal investigator: Yongsheng Wang — West China Hospital
• Study coordinator: Yue Chen, PhD

Conditions Non-Small Cell Lung Cancer