A Study of BL-M07D1 in Combination With Pembrolizumab in Patients With Unresectable Locally Advanced or Metastatic HER2-Overexpressing Non-Squamous NSCLC

Official title

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

Overview

This trial is a multicenter, open-label, Phase II clinical study to explore the efficacy and safety of BL-M07D1 in combination with pembrolizumab in patients with locally advanced or metastatic HER2-overexpressing non-squamous non-small cell lung cancer.

Interventions

• Drug BL-M07D1
  Administration by intravenous infusion for a cycle of 3 weeks.
• Drug Pembrolizumab
  Administration by intravenous infusion for a cycle of 3 weeks.

Primary outcome measures

• Objective Response Rate (ORR) [Time frame: Up to approximately 24 months]
• Combined optimal dosage [Time frame: Up to approximately 24 months]
• Combination method [Time frame: Up to approximately 24 months]

Secondary outcome measures (10)

• Progression-free Survival (PFS) [Time frame: Up to approximately 24 months]
• Disease Control Rate (DCR) [Time frame: Up to approximately 24 months]
• Duration of Response (DOR) [Time frame: Up to approximately 24 months]
• Overall survival (OS) [Time frame: Up to approximately 24 months]
• Cmax [Time frame: Up to approximately 24 months]
• Tmax [Time frame: Up to approximately 24 months]
• Ctrough [Time frame: Up to approximately 24 months]
• Anti-drug antibody (ADA) [Time frame: Up to approximately 24 months]
• Drug-drug interactions (DDI) [Time frame: Up to approximately 24 months]
• Treatment-Emergent Adverse Event (TEAE) [Time frame: Up to approximately 24 months]

Eligibility criteria

Inclusion criteria

• Voluntarily sign the informed consent form and comply with the protocol requirements;
• No gender restrictions;
• Age at the time of signing the informed consent form ≥18 years and ≤75 years;
• Expected survival time ≥3 months;
• Patients with locally advanced or metastatic non-squamous non-small cell lung cancer;
• Confirmed known HER2 overexpression;
• Agree to provide archived tumor tissue specimens from primary or metastatic lesions within the past 2 years;
• Must have at least one measurable lesion meeting the RECIST v1.1 criteria;
• ECOG performance status score of 0 or 1;
• Toxicities from prior anti-tumor treatments have recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
• No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
• Organ function levels must meet the requirements;
• 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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and — Wuhan

Identifiers

NCT: NCT07264816 · BL-M07D1-207

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗