BL-M07D1 versus pembrolizumab-plus-platinum chemo for first-line HER2‑mutant advanced non-squamous lung cancer

A Randomized Controlled Phase III Clinical Study of BL-M07D1 vs Pembrolizumab-platinum Chemotherapy in First-line Treatment of HER2-mutant Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer

This trial will test whether BL-M07D1 works better than pembrolizumab combined with platinum chemotherapy as the first treatment for people with HER2‑mutant advanced or metastatic non-squamous non-small cell lung cancer.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 440 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd. (industry)
• Drugs / interventions: immunotherapy, prednisone
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT07178795 on ClinicalTrials.gov

What this trial studies

This is a randomized, open-label, phase 3 multicenter trial comparing the investigational agent BL-M07D1 to pembrolizumab plus platinum chemotherapy (with pemetrexed) as first-line therapy for HER2‑mutant advanced or metastatic non-squamous NSCLC. Eligible patients must have centrally confirmed HER2 functional mutations, measurable disease by RECIST v1.1, and an ECOG performance status of 0 or 1. The study will follow patients for efficacy and safety outcomes, including tumor response and survival endpoints, with safety monitoring per standard oncology practice. Enrollment is limited to adults who meet laboratory and organ-function requirements and who have recovered from prior treatment toxicities to allowed levels.

Who should consider this trial

Good fit: Ideal candidates are adults (18–75 years) with centrally confirmed HER2‑mutant advanced or metastatic non-squamous NSCLC, measurable disease, ECOG 0–1, adequate organ function, and no unresolved high-grade toxicity from prior therapies.

Not a fit: Patients with squamous histology, those who have received prior systemic therapy for advanced disease, those with poor performance status or significant organ dysfunction, and pregnant individuals are unlikely to qualify or benefit from this trial.

Why it matters

Potential benefit: If successful, BL-M07D1 could offer a more effective or better tolerated first-line treatment option for people with HER2‑mutant advanced non-squamous NSCLC.

How similar studies have performed: Other HER2‑targeted drugs (for example antibody–drug conjugates) have shown benefit in HER2‑mutant lung cancer and pembrolizumab-plus-platinum chemotherapy is an established first-line option, but BL-M07D1 itself is a novel agent being tested in this setting.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily sign the informed consent form and comply with the protocol requirements;
2. Age at the time of signing the informed consent form is ≥18 years and ≤75 years, regardless of gender;
3. Expected survival time ≥12 weeks;
4. Histologically or cytologically confirmed advanced or metastatic non-squamous non-small cell lung cancer;
5. HER2 functional mutation confirmed by a central laboratory;
6. Provide the most recent tumor tissue meeting the requirements for biomarker testing by the central laboratory;
7. Must have at least one measurable target lesion as defined by RECIST v1.1;
8. ECOG performance status score of 0 or 1;
9. Toxicity from previous anti-tumor treatments has recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
10. Organ function levels must meet the requirements;
11. For premenopausal women with childbearing potential, a pregnancy test must be conducted within 7 days prior to the start of treatment, and the serum pregnancy test must be negative. They must not be breastfeeding. All enrolled patients (regardless of gender) should take adequate and highly effective contraceptive measures throughout the treatment period and for 7 months after the end of treatment.

Exclusion Criteria:

1. Having undergone surgical treatment, radical radiotherapy, immunotherapy, etc., within 4 weeks prior to the first dose or within 5 half-lives;
2. Pathological findings indicating non-small cell carcinoma containing small cell carcinoma components and sarcomatoid carcinoma;
3. Concurrent presence of other driver gene mutations for which targeted drug therapy is available and approved for NSCLC indications;
4. Previous treatment with HER2-targeted therapy or ADC drugs with camptothecin derivatives as the toxin;
5. History of severe cardiovascular or cerebrovascular diseases within the past 6 months prior to screening;
6. Concurrent pulmonary diseases leading to severe impairment of lung function;
7. History of ILD/interstitial pneumonia requiring steroid treatment or current diagnosis of ILD/interstitial pneumonia;
8. Prolonged QT interval, complete left bundle branch block, third-degree atrioventricular block, frequent and uncontrollable arrhythmias;
9. Diagnosis of other primary malignancies within 5 years prior to the first dose;
10. Newly developed deep vein thrombosis within 14 days prior to screening;
11. Hypertension poorly controlled by antihypertensive medications;
12. Patients with central nervous system (CNS) metastases, carcinomatous meningitis (leptomeningeal metastases), and/or spinal cord compression;
13. Patients with a history of severe allergies to any excipients or components of the investigational drug;
14. History of autologous or allogeneic stem cell transplantation or organ transplantation;
15. Positive human immunodeficiency virus antibody, active hepatitis B virus infection, liver cirrhosis, or hepatitis C virus infection;
16. Occurrence of severe infections within 4 weeks prior to the first use of the investigational drug;
17. Patients with significant serous cavity effusion, symptomatic serous cavity effusion, or poorly controlled serous cavity effusion;
18. Systemic corticosteroid treatment with \>10 mg/d prednisone or equivalent prior to randomization;
19. Presence of severe neurological or psychiatric disorders;
20. Subjects with clinically significant bleeding or obvious bleeding tendencies within 4 weeks prior to signing informed consent;
21. Conditions such as intestinal obstruction, Crohn's disease, ulcerative colitis, or chronic diarrhea;
22. Subjects planning to receive or having received live vaccines within 28 days prior to the first dose;
23. Presence of other severe physical or laboratory abnormalities, poor compliance, or any other factors that may increase the risk of participation in the study, interfere with study results, or make the patient unsuitable for participation in the study as determined by the investigator.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Study coordinator: Sa Xiao, PHD

Conditions: Non-squamous Non-small Cell Lung Cancer