Clinical trial NCT05949619: A Study of BL-M02D1 in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer or Other Solid Tumors
Official title: A Phase Ib/II Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of BL-M02D1 for Injection in Patients With Multiple Solid Tumors, Including Locally Advanced or Metastatic Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-07-18
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase Ib: To explore the safety and preliminary efficacy of BL-M02D1 to further define RP2D in a variety of solid tumors such as locally advanced or metastatic non-small cell lung cancer. Phase II: To explore the efficacy of BL-M02D1 using single-agent RP2D obtained from phase I clinical studies.


Eligibility criteria: Inclusion Criteria:

1. Voluntarily sign the informed consent and follow the requirements of the protocol;
2. No gender limit;
3. Age: ≥18 years old;
4. expected survival time ≥3 months;
5. Histologically and/or cytologically confirmed locally advanced or metastatic non-small cell lung cancer and other solid tumors that have failed standard treatment;
6. Consent to provide archival tumor tissue specimens (10 unstained sections (anti-slip) surgical specimens (thickness 4-5μm)) or fresh tissue samples from primary or metastatic lesions within 3 years. If participants cannot provide tumor tissue samples, they can be enrolled if they meet other inclusion and exclusion criteria, after the evaluation of the investigator;
7. Must have at least one measurable lesion according to RECIST v1.1 definition;
8. ECOG 0 or 1;
9. Toxicity from previous antineochemical therapy has returned to grade 1 or less as defined by NCI-CTCAE v5.0 (asymptomatic laboratory abnormalities such as elevated ALP, hyperuricemia, elevated serum amylase/lipase, and elevated blood glucose were considered by the investigator, and toxicity with no safety risk was judged by the investigator; Excluding alopecia, grade 2 peripheral neurotoxicity, hypothyroidism stabilized by hormone replacement therapy, or decreased hemoglobin (≥90g/L).
10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
11. The level of organ function must meet the following requirements and meet the following standards:

    1. Bone marrow function: absolute neutrophil count (ANC) ≥1.5×109/L, platelet count ≥100×109/L, hemoglobin ≥90 g/L;
    2. Liver function: total bilirubin (TBIL≤1.5 ULN), AST and ALT ≤2.5 ULN in patients without liver metastasis, AST and ALT ≤5.0 ULN in patients with liver metastasis;
    3. Renal function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to Cockcroft and Gault formula).
12. Coagulation function: international normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5ULN;
13. Urine protein ≤2+ or ≤1000mg/24h;
14. Female subjects of childbearing potential or male subjects with a fertile partner must use highly effective contraception from 7 days before the first dose until 6 months after the dose. Female subjects of childbearing potential had to have a negative serum pregnancy test within 7 days before the first dose.

Exclusion Criteria:

1. Antineoplastic therapy, including chemotherapy, biologic therapy, immunotherapy, definitive radiotherapy, major surgery (investigator-defined), or targeted therapy (including small-molecule tyrosine kinase inhibitors), has been administered within 4 weeks or 5 half-lives (whichever is shorter) before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral fluorouracil drugs such as S-1, capecitabine, or palliative radiotherapy within 2 weeks before the first dose; The TCM with anti-tumor indications was within 2 weeks before the first administration.
2. Prior treatment with Trop2-targeted ADC drugs or with camptothecin derivatives (topoisomerase I inhibitors) as toxins;
3. 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, third degree atrioventricular block, complete left bundle branch block, frequent and uncontrollable arrhythmias, such as atrial fibrillation, atrial flutter, ventricular fibrillation, and ventricular flutter (except transient);
   2. prolonged QT interval at rest (QTc \> 450 msec in men or QTc \> 470 msec in women);
   3. acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months before the first dose;
   4. patients with New York Heart Association (NYHA) functional class ≥II heart failure;
4. 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 were type I diabetes, hypothyroidism that was stable with hormone-replacement therapy (including that due to autoimmune thyroid disease), psoriasis or vitiligo that did not require systemic therapy, and hypothyroidism that was stable with hormone-replacement therapy.
5. 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;
6. Unstable deep vein thrombosis, arterial thrombosis, and pulmonary embolism requiring medical intervention within 6 months before screening; Infusion-related thrombosis was excluded.
7. Patients with massive or symptomatic effusions, or poorly controlled effusions (poorly controlled was defined as requiring 2 or more paracentesis within a month).
8. Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure \&gt; 150 mmHg or diastolic blood pressure \&gt; 100 mmHg);
9. Current interstitial lung disease, drug-induced interstitial pneumonia, radiation pneumonitis requiring steroid therapy, or a history of these diseases;
10. Patients with central nervous system (CNS) metastases and/or carcinomatous meningitis (meningeal metastases). Patients who had received treatment for brain metastases (radiotherapy or surgery; Patients with stable brain metastases who had stopped radiotherapy or surgery 28 days before the first dose were eligible. Patients with cancerous meningitis (meningeal metastasis) were excluded even if they were treated and judged to be stable. Stable disease was defined as being asymptomatic, in stable condition, and not requiring steroid therapy for more than 4 weeks before starting study treatment.
11. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or any of the excipients of BL-M02D1;
12. Previous history of allogeneic stem cell, bone marrow, or organ transplantation;
13. 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);
14. 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;
15. A history of autologous or allogeneic stem cell transplantation;
16. Pregnant or lactating women;
17. Other conditions for participation in the trial were not considered appropriate by the investigator.

Primary outcomes:
measure: Phase Ib: Recommended Phase II Dose (RP2D)
timeFrame: Up to 21 days after the first dose
measure: Phase II: Objective Response Rate (ORR)
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 24 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 24 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Objective Response Rate (ORR)
timeFrame: Up to approximately 24 months
measure: Phase II: Progression-free Survival (PFS)
timeFrame: Up to approximately 24 months
measure: Cmax
timeFrame: Up to 21 days after the first dose
measure: Tmax
timeFrame: Up to 21 days after the first dose
measure: Ctrough
timeFrame: Up to 21 days after the first dose
measure: Phase Ib: T1/2
timeFrame: Up to 21 days after the first dose
measure: Phase Ib: AUC0-T
timeFrame: Up to 21 days after the first dose
measure: Phase Ib: CL
timeFrame: Up to 21 days after the first dose
measure: ADA (anti-drug antibody)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Pulmonary Hospital, Shanghai, China
name: Caicun Zhou, PHD
role: PRINCIPAL_INVESTIGATOR
References: