The Phase I Clinical Study of the Inhaled mRNA Tumor-associated Antigen Dry Powder Vaccine BMD006 in Patients With Advanced Lung Cancer or Metastatic Solid Tumors in the Lungs.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 83
- 试验地点
- 1
- 主要终点
- Number of participants experiencing dose-limiting toxicities（DLTs）
研究概览
简要总结
BMD006 is an inhaled mRNA tumor-associated antigen dry powder vaccine targeting lung cancer and solid tumors with lung metastasis, classified as an off-the-shelf anti-tumor product. The product contains two clinically validated TAA antigen combinations: for patients with solid tumors that have lung metastasis, the mRNA vaccine consists of four mRNA sequences encoding melanoma-associated tumor antigens ; for patients with primary lung cancer, the mRNA vaccine consists of six mRNA sequences encoding tumor-associated antigens of primary lung cancer .
This study is a single-center, open-label, dose-escalation trial designed to evaluate the safety, tolerability, preliminary efficacy, PK, and PD of BMD006 in patients with advanced lung cancer or advanced solid tumors with lung metastasis who have failed standard treatments or have no standard treatment options. Additionally, the study will further explore the effect of BMD006 in combination with PD-1 or Ivonescimab Injection treatment.
详细描述
This study adopts a single center, open label, dose escalation design to evaluate the safety, tolerability, preliminary efficacy, PK and PD characteristics of BMD006 in patients with advanced lung cancer or advanced solid tumors with lung metastasis who have failed standard treatment or have no standard treatment, and to explore the treatment of BMD006 PD-1 or PD-1/VEGF.
This study includes three parts: exploring the dosage of BMD006 alone, exploring the dosage of BMD006 combined with PD-1 or PD-1/VEGF, and expanding the dosage of BMD006 combined with PD-1/VEGF.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 99 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to understand and comply with the requirements of the study protocol, voluntarily participate in the trial, and sign a written informed consent form (ICF).
- •Must be at least 18 (inclusive) at the time of signing the ICF, and both male and female participants are eligible.
- •Histologically or cytologically confirmed as advanced lung cancer (driver gene negative) or advanced solid tumors with lung metastasis, and having failed prior standard treatments or having no standard treatment options.
- •Agree to provide fresh tumor tissue samples or archived tumor tissue samples within the past three years.
- •Presence of at least one measurable lesion as defined by RECIST V1.1
- •Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1
- •Organ function must be adequate at screening (no need for blood transfusion, hematopoietic growth factors, human albumin, or medications for correction within 14 days prior to first treatment), specifically defined as: a) Hematology: Absolute neutrophil count ≥1.5×10^9/L; platelet count ≥90×10^9/L; hemoglobin ≥90 g/L (9 g/dL). b) Liver Function: Serum total bilirubin (TBIL) ≤1.5× upper limit of normal (ULN); for patients with liver metastasis or a history/suspected history of Gilbert's syndrome (persistent or recurrent hyperbilirubinemia, primarily unconjugated bilirubin, with no evidence of hemolysis or liver pathology), TBIL ≤3×ULN; for patients without liver metastasis, alanine aminotransferase (ALT) and aspartate aminotransferase (AST); for patients with liver metastasis, ALT or AST ≤5×ULN. c) Renal Function: Creatinine (Cr) ≤1.5×ULN or creatinine clearance (CLcr) ≥60 mL/min (calculated using the Cockcroft-Gault formula, see Attachment 3); urine dipstick test result showing urinary protein <2+; for patients with baseline urine dipstick showing protein ≥2+, a 24-hour urine collection should be conducted, and the protein content in the 24-hour urine should be <1 g. d) Cardiac Function: Echocardiography showing left ventricular ejection fraction (LVEF) >50%. e) Pulmonary Function: Shortness of breath ≤Grade 1 as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), and outdoor ambient air oxygen saturation (SpO₂) ≥92%.
- •Expected life expectancy ≥12 weeks.
- •Female patients of childbearing potential and male patients (and their female partners) must use highly effective contraception from the screening period until at least 6 months after the last dose of the study drug. Patients must not plan to conceive, donate sperm, or donate eggs during this period
排除标准
- •Patients with lung cancer who have concurrent other types of malignant tumors or are diagnosed with multiple primary malignancies, except for the following: completely resected basal cell carcinoma and squamous cell carcinoma of the skin, completely resected any type of carcinoma in situ.
- •Symptomatic central nervous system metastasis; for patients with asymptomatic brain metastasis or those whose symptoms have been stable for ≥2 weeks after treatment of brain metastasis, they may participate in this study if they meet all the following criteria: measurable lesions in the lungs; cessation of steroid treatment 14 days prior to the first trial product dose.
- •Patients with chronic obstructive pulmonary disease (COPD), asthma, or allergies to pollen or dust.
- •Patients suspected of having active or latent tuberculosis infection, based on interferon-γ release assay results, clinical symptoms, and/or chest imaging findings (patients with evidence of adequately treated prior active tuberculosis infection may be enrolled after assessment by the investigator; for latent tuberculosis, patients must have completed at least 4 weeks of anti-tuberculosis treatment, with no liver function impairment [ALT ≤3×ULN, AST ≤3×ULN], and after the investigator assesses that the risk is manageable, they may be considered for continued screening or enrollment).
- •History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis or organizing pneumonia), or active, non-infectious pneumonia requiring immunosuppressive treatment such as corticosteroids.
- •Patients with active autoimmune diseases requiring therapeutic intervention.
- •History of serious bleeding disorders; or those with coagulation dysfunction (as indicated by laboratory tests or medical history) who are deemed by the investigator to be unsuitable for the trial treatment.
- •History or current diagnosis of cardiovascular disease, including any of the following: a) Recent myocardial infarction or coronary artery bypass grafting (CABG) within the past 6 months; b) Uncontrolled congestive heart failure; c) Unstable angina (within the past 6 months); d) Clinically significant (symptomatic) arrhythmias (e.g., sustained ventricular tachycardia, clinically significant second- or third-degree atrioventricular block without a pacemaker).
- •Clinically uncontrolled third-space fluid accumulation (e.g., pleural effusion/pericardial effusion; patients with effusions that do not require drainage or those whose effusions have not increased significantly after stopping drainage for 3 days may be included).
- •Severe infection requiring intravenous antibiotic treatment or hospitalization at screening, or any uncontrolled active infection within 4 weeks prior to the first dose of the trial product.
- •History of severe allergic reactions, or known allergy to any active or inactive component of BMD006 or PD-1 inhibitors.
- •Any other metabolic, hematological, renal, hepatic, pulmonary, neurological, endocrine, cardiac, or gastrointestinal disease that, in the investigator's opinion, may present unacceptable risks to the patient during treatment.
- •Presence of unresolved toxicity from prior anti-tumor treatments before the first dose of the study product, which has not recovered to Grade 0 or 1 (excluding alopecia) (severity assessed according to NCI CTCAE v5.0).
- •Positive test results for hepatitis B at screening [defined as: ① Hepatitis B surface antigen (HBsAg) positive; ② HBsAg negative but hepatitis B core antibody (HbcAb) positive (further testing through hepatitis B virus deoxyribonucleic acid [HBV DNA] is required, and patients with HBV DNA levels exceeding the normal limit for the test method must be excluded)], positive hepatitis C antibody (HCV Ab) [further testing through hepatitis C virus ribonucleic acid (HCV RNA) is required, and patients with HCV RNA levels exceeding the normal limit for the test method must be excluded], or positive human immunodeficiency virus antibody (HIV Ab).
- •Underwent major surgery within 4 weeks prior to the first dose of the trial product (cranial, thoracic, or abdominal surgery) or has an unresolved wound, ulcer, or fracture. Note: Thoracoscopic surgery and mediastinoscopy will not be considered major surgery. Patients who are ≥2 weeks post-surgery or who are deemed eligible by the investigator may be included in the study.
- •Previously received similar products or treatments.
- •Received other anti-tumor treatments (radiotherapy, chemotherapy, endocrine therapy, targeted therapy, immunotherapy, etc.) within 4 weeks or 5 half-lives (whichever is longer) prior to the first dose of the trial product.
- •Received systemic immunosuppressive agents (e.g., systemic corticosteroids) within 3 months prior to the first dose of the trial product.
- •Received or planned to receive live or attenuated live vaccines within 3 months prior to the first dose of the trial product or during the study.
- •Pregnant or breastfeeding women.
- •Participated in any clinical drug trial (defined as being randomized and receiving trial product treatment) within 3 months or 5 half-lives (whichever is longer) prior to screening.
- •Any other condition deemed by the investigator to make the patient unsuitable for participation in the trial.
研究组 & 干预措施
BMD006 monotreatment
BMD006 is packaged in capsules and contains white powder. Under no circumstances should it be swallowed, and only the Breezhaler inhalation device (consisting of a dust cap, nozzle, base, puncture button, and central chamber) should be used for inhalation therapy.
BMD006 monotreatment is treated on D1, D15, and D22, and D28 is evaluated by investigators to be safe and tolerable. The patient will continue to receive QW treatment at the current dose level for 6 times, and then switch to Q3W treatment until 52 weeks after the first treatment or reaching the termination criteria.
干预措施: BMD006 monotreatment (Biological)
BMD006 in combination with PD-1or PD-1/VEGF antibody
BMD006 was treated at D1, D8, and D15, and D21 was evaluated by researchers to be safe and tolerable. The patient will continue to receive QW treatment at the current dose level for 6 times, and then switch to Q3W treatment until 52 weeks after the first treatment or until the termination criteria are met in BMD006 in combination with PD-1 or PD-1/VEGF antibody.
PD-1 antibodies will be used according to medical advice and instructions.
干预措施: BMD006 in combination with PD-1 antibody (Biological)
BMD006 in combination with PD-1/VEGF antibody
The subjects will be randomly assigned in a 1:1 ratio to either the BMD006 and PD-1/VEGF group (Group 1) or the BMD006 monotherapy group for six weeks plus two drugs combination therapy group (Group 2). The ratio of the two groups will be 1:1, with no less than 10 patients in each group.
The first group is a combination therapy of BMD006 and PD-1/VEGF. BMD006 is administered once a week for the first six weeks, and will be adjusted to once every three weeks starting from the seventh week. PD-1/VEGF is administered once every three weeks. The second group received BMD006 monotherapy once a week, and after six doses, the researchers evaluated the potential benefits. Starting from the seventh week, BMD006 was used in combination with PD-1/VEGF, and thereafter BMD006 was used every three weeks, while PD-1/VEGF was used every three weeks.
干预措施: BMD006 in combination with PD-1/VEGF antibody (Biological)
结局指标
主要结局
Number of participants experiencing dose-limiting toxicities（DLTs）
时间窗: about 2 years
Number of participants experiencing dose-limiting toxicities（DLTs）
Determine the maximum tolerated dose（MTD） of BMD006
时间窗: about 2 years
Determine the maximum tolerated dose（MTD） of BMD006
Determine the recommended phase II dose (RP2D) for the clinical study.
时间窗: about 2 years
Determine the recommended phase II dose (RP2D) for the clinical study.
number of participants experiencing adverse events（AEs）
时间窗: about 2 years
number of participants experiencing adverse events（AEs）
次要结局
- The proportion and activation status of antigen-specific T cells in peripheral blood and tumor tissue (if available)(about 2 years)
- The titers of antigen-specific antibodies IgG and IgA in serum(about 2 years)
- overall response rate（ORR）(Up to 12 months)
- Disease Control Rate(DCR)(Up to 12 months)
- Duration of Response(DOR)(Up to 12 months)
- Progression-Free Survival (PFS)(Up to 12 months)
- Overall Survival(OS)(Up to 12 months)
- The 6-month and 12-month overall survival (OS) rates.(Up to 6 or 12 months)