BL-M07D1 plus pembrolizumab for advanced HER2‑overexpressing non-squamous NSCLC

A Phase II Clinical Study to Evaluate the Efficacy and Safety of BL-M07D1 in Combination With Pembrolizumab in Patients With Unresectable Locally Advanced or Metastatic HER2-Overexpressing Non-Squamous Non-Small Cell Lung Cancer

This treatment combines BL-M07D1 with pembrolizumab to see if it helps people with unresectable locally advanced or metastatic HER2‑overexpressing non‑squamous non‑small cell lung cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: pembrolizumab, immunotherapy
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT07264816 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label Phase II trial testing the safety and anti-tumor activity of the investigational agent BL‑M07D1 given together with pembrolizumab in patients with unresectable locally advanced or metastatic HER2‑overexpressing non‑squamous NSCLC. Eligible participants must have confirmed HER2 overexpression, at least one measurable lesion per RECIST v1.1, ECOG 0–1, adequate organ function, and recoveries from prior treatment toxicities. Archived tumor tissue is required for biomarker confirmation, and cardiac function must be acceptable (LVEF ≥50%). The trial will monitor tumor responses and adverse events to characterize tolerability and preliminary efficacy of the combination.

Who should consider this trial

Good fit: Adults aged 18–75 with unresectable locally advanced or metastatic non-squamous NSCLC, confirmed HER2 overexpression, measurable disease, ECOG performance status 0–1, and adequate organ and cardiac function are ideal candidates.

Not a fit: Patients without HER2 overexpression, with ECOG >1, unresolved ≥Grade 2 toxicities from prior therapy, significant cardiac dysfunction (LVEF <50%), or insufficient organ function are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the combination could improve tumor control and extend the time patients live without disease progression compared with current options for this HER2‑overexpressing population.

How similar studies have performed: Other early‑phase efforts combining HER2‑directed agents with PD‑1/PD‑L1 inhibitors in HER2‑altered lung cancers have shown mixed but occasionally promising responses, so this approach is under active investigation.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily sign the informed consent form and comply with the protocol requirements;
2. No gender restrictions;
3. Age at the time of signing the informed consent form ≥18 years and ≤75 years;
4. Expected survival time ≥3 months;
5. Patients with locally advanced or metastatic non-squamous non-small cell lung cancer;
6. Confirmed known HER2 overexpression;
7. Agree to provide archived tumor tissue specimens from primary or metastatic lesions within the past 2 years;
8. Must have at least one measurable lesion meeting the RECIST v1.1 criteria;
9. ECOG performance status score of 0 or 1;
10. Toxicities from prior anti-tumor treatments have recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
11. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
12. Organ function levels must meet the requirements;
13. For premenopausal women with childbearing potential, a pregnancy test must be conducted within 7 days before starting treatment, serum pregnancy must be negative, and they must not be breastfeeding; all enrolled patients (regardless of gender) should take adequate and highly effective contraception throughout the treatment cycle and for 7 months after the end of treatment.

Exclusion Criteria:

1. Underwent surgical treatment, radical radiotherapy, immunotherapy, etc., within 4 weeks before the first dose or within 5 half-lives;
2. Pathology indicates non-small cell carcinoma containing small cell carcinoma components and sarcomatoid carcinoma;
3. Previously received HER2-targeted therapy or ADC drug treatment with camptothecin derivatives as toxins;
4. History of severe cardiovascular or cerebrovascular diseases within the past 6 months before screening;
5. Concurrent pulmonary disease leading to severe impairment of lung function;
6. QT interval prolongation, complete left bundle branch block, third-degree atrioventricular block, frequent and uncontrollable arrhythmias;
7. Diagnosed with other primary malignancies within 5 years before the first dose;
8. Poorly controlled hypertension;
9. History of non-infectious ILD requiring steroid treatment, or currently suffering from ILD/interstitial pneumonia, etc.;
10. Patients with central nervous system metastases, carcinomatous meningitis, and/or spinal cord compression;
11. Patients with a history of allergy to recombinant humanized antibodies or allergy to BL-M07D1, pembrolizumab, or any excipient components;
12. Required systemic corticosteroid or immunosuppressive therapy within 2 weeks before the study administration;
13. Patients with massive serous cavity effusion, symptomatic serous cavity effusion, or poorly controlled serous cavity effusion;
14. New deep vein thrombosis within 14 days, excluding patients with venous filters implanted;
15. Systemic severe infection within 4 weeks before screening;
16. Active autoimmune diseases and inflammatory diseases;
17. Human immunodeficiency virus antibody positivity, active hepatitis B virus infection, or hepatitis C virus infection;
18. History of allogeneic stem cell, bone marrow, or organ transplantation;
19. Presence of severe neurological or psychiatric disorders;
20. Presence of other severe physical or laboratory abnormalities, poor compliance, etc., which may increase the risk of participation in the study, interfere with study results, or patients deemed unsuitable for participation in the study by the investigator.

Where this trial is running

Wuhan, Hubei

• Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)

Study contacts

• Study coordinator: Sa Xiao, PHD

Conditions Non-squamous Non-small Cell Lung Cancer