Study to Evaluate BL-B01D1 in Patients With Metastatic or Unresectable Non-Small Cell Lung Cancer (NSCLC)
Study Details
Study Description
Brief Summary
The objective of this study is to evaluate the safety, tolerability, and efficacy of BL-B01D1 in patients with Metastatic or Unresectable Non-Small Cell Lung Cancer (NSCLC).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
BL-B01D1-LUNG-101 is a global, multi-center, Phase 1 study to evaluate the safety, tolerability, pharmacokinetics , and initial efficacy of BL-B01D1 in participants with metastatic or unresectable NSCLC.
This study will be conducted in two different dosing schedules (Cohort A and Cohort B) and three parts (dose escalation, dose finding and dose expansion). Cohort A will be dosed on Day 1 and Day 8 of a continuous 21-day treatment cycle. Cohort B will be dosed on Day 1 of a continuous 21-day treatment cycle. Each Cohort has different dose groups.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BL-B01D1 administered Day 1 and Day 8 per cycle BL-B01D1 will be administered on Day 1 and Day 8 by intravenous infusion every 3 weeks |
Drug: BL-B01D1
The study includes 3 parts: Part 1 Dose escalation. Part 2 Dose Finding non-randomized and Part 3 Dose expansion randomized.
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| Experimental: BL-B01D1 administered Day 1 per cycle BL-B01D1 will be administered on Day 1 via by intravenous infusion every 3 weeks |
Drug: BL-B01D1
The study includes 3 parts: Part 1 Dose escalation. Part 2 Dose Finding non-randomized and Part 3 Dose expansion randomized.
|
Outcome Measures
Primary Outcome Measures
- Participants with Dose-limiting toxicities [One year]
Measuring the number of patients Dose-limiting toxicities (DLTs). A DLT is defined as any of the following events that are not clearly due to the underlying disease or extraneous causes: Hematological toxicities: Grade 4 neutrophil count decreased lasting >7 days Grade ≥3 febrile neutropenia Grade ≥3 platelet count decreased with clinically significant hemorrhage. Non-Hematological toxicities: Death Hy's law cases Grade ≥3 non-hematological toxicities,
- Participants with Serious Adverse Events (SAEs) and treatment-emergent adverse events (TEAEs), [One year]
Measuring the number of patients with serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs)
- Participants with abnormal physical examination findings [One year]
Measure the number of participants with abnormal physical examination findings.
- Participants with ability to care for themselves, daily activity, and physical activity [One year]
Measure the change in participants with Eastern Clinical Oncology Group (ECOG) Scale of Performance Status. The scale is 0-4 with 0 being the fully active (best outcome) and 4 being completely disabled (worst outcome)
- Participants with abnormal ECG reading [One year]
Measure the number of participants with abnormal ECG parameters
- Participants with abnormal lab results [One year]
Measure the number of participants with abnormal clinical laboratory values
- To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and two or more recommended doses and schedules for recommended dose expansion (RDEs) of BL-B01D1 in metastatic NSCLC [One year]
Determine the highest BL-B01D1 dose level at which ≤33% subjects experience a DLT during the DLT evaluation period and highest BL-B01D1 dose administered in the event and MTD cannot be defined.
Secondary Outcome Measures
- Cmax of BL-B01D1 [One year]
Calculate maximum (peak) observed concentration of BL-B01D1
- Cmax of anti-EGFR×HER3 antibody [One year]
Calculate maximum (peak) observed concentration of anti-EGFR×HER3 antibody
- Cmax of free payload ED-04 [One year]
Calculate maximum (peak) observed concentration of free payload ED-04
- Tmax of BL-B01D1 [One year]
Calculate time of maximum observed concentration of BL-B01D1
- Tmax of anti-EGFR×HER3 antibody [One year]
Calculate time of maximum observed concentration of anti-EGFR×HER3 antibody
- Tmax of free payload ED-04 [One year]
Calculate time of maximum observed concentration of free payload ED-04
- AUC(0-8) of BL-B01D1 [One year]
Calculate area under the serum concentration-time curve of BL-B01D1 from time 0 to 8 hours
- AUC(0-8) of anti-EGFR×HER3 antibodies [One year]
Calculate area under the serum concentration-time curve of anti-EGFR×HER3 antibodies from time 0 to 8 hours
- AUC(0-8) of free payload ED-04 [One year]
Calculate area under the serum concentration-time curve of free payload ED-04 from time 0 to 8 hours
- AUC(last) of BL-B01D1 [One year]
Calculate area under the serum concentration-time curve up of BL-B01D1 to the last quantifiable time
- AUC(last) anti-EGFR×HER3 antibodies [One year]
Calculate area under the serum concentration-time curve up of anti-EGFR×HER3 antibodies to the last quantifiable time
- AUC(last) of free payload ED-04 [One year]
Calculate area under the serum concentration-time curve up of free payload ED-04 to the last quantifiable time
- Overall Response Rate (ORR) [One year]
To assess the clinical efficacy of BL-B01D1 as measured by ORR using RECIST criteria v 1.1
- Disease Control Rate (DCR) [One year]
To assess the clinical efficacy of BL-B01D1 as measured by DCR using RECIST criteria v 1.1
- Time To Response (TTR) [One year]
To assess the clinical efficacy of BL-B01D1 as measured by TTR using RECIST criteria v 1.1
- Progression-Free Survival (PFS), [One year]
To assess the clinical efficacy of BL-B01D1 as measured by PFS using RECIST criteria v 1.1
- Overall Survival (OS). [One year]
To assess the clinical efficacy of BL-B01D1 as measured by OS using RECIST criteria v 1.1
Eligibility Criteria
Criteria
Inclusion Criteria:
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Signed the informed consent voluntarily and agreed to follow the program requirements
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Either sex
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Age: ≥18 years
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Has a life expectancy of ≥3 months
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Has documented locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation with documentation of radiological disease progression while on/after receiving most recent treatment regimen for locally advanced or metastatic disease. Subjects must have received the following treatments based on Actionable Genomic
Alterations (AGA):
- Subjects without AGA: Must have documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Must have no known genomic alterations in ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), mesenchymal-epithelial transition (MET) exon 14 skipping, or rearranged during transfection (RET) and Kirsten rat sarcoma viral oncogene homolog mutations (KRAS)
They must meet 1 of the following prior therapy requirements for locally advanced or metastatic NSCLC:
Received and refractory to at least one platinum-based chemotherapy with α-PD-1/L1 monoclonal antibody given either concurrently or in separate lines of therapy. Includes subjects who received prior platinum-based chemotherapy with or without radiotherapy with maintenance α-PD-1/L1 monoclonal antibody for Stage 3 disease and relapsed /progressed within 6 months from the last dose of platinum-based chemotherapy. Includes subjects who received prior platinum-based/chemotherapy with or without radiotherapy (with or without maintenance α-PD-1/L1 monoclonal antibody) for Stage 3 disease and subsequently received α-PD-1/L1 monoclonal antibody therapy (with or without platinum-based chemotherapy) for recurrent disease. Received platinum-based chemotherapy and α-PD-1/L1 monoclonal antibody (in either order) sequentially
- Subjects with AGA must have one or more documented actionable genomic alteration(s): EGFR, ALK, ROS1, NTRK, BRAF, KRAS, MET exon 14 skipping, or RET and must meet the following for advanced or metastatic NSCLC:
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Subjects must have been treated and refractory with 1 or more prior lines of applicable targeted therapy that is locally approved for the participant's genomic alteration at the time of screening; subjects who have tumors with EGFR L858R or Exon 19 deletion mutations must have received and be considered refractory to prior osimertinib therapy. Those who received a targeted agent as adjuvant therapy for early-stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of targeted therapy for the same genomic alteration (which may or may not be same agent used in the adjuvant setting) for relapsed/progressive disease. Subjects who have been treated and are refractory to a prior TKI must receive additional approved targeted therapy, if locally available and clinically appropriate, for the applicable genomic alteration
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Subjects with ROS1, NTRK, BRAF, KRAS, MET exon 14 skipping, or RET must have received and be refractory to or be ineligible for at least one platinum-based chemotherapy. For subjects with EGFR or ALK prior treatment with platinum-based chemotherapy is considered optional. Those who received a platinum-containing regimen as adjuvant therapy for early-stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose OR received at least one additional course of platinum-containing therapy (which may or may not be same as in the adjuvant setting) for relapsed/progressive disease and may have received and be refractory to one or more α-PD-1/L1 monoclonal antibody alone or in combination with a cytotoxic agent
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Agree to provide archived tumor samples or fresh samples from primary or metastatic sites within 2 years; If subjects are unable to provide tumor samples, they will be admitted after evaluation by the investigator if other admission criteria are met
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Has at least one measurable lesion based on RECIST V1.1
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Has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1
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Toxicity of previous antitumor therapy has returned to level ≤1 as defined by NCI-CTCAE V5.0 (except for asymptomatic laboratory abnormalities such as elevated ALP, hyperuricemia, elevated serum amylase/lipase, and elevated blood glucose; except for toxicity that the investigator determined to have no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, hypothyroidism stabilized by hormone replacement therapy, etc.)
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Has no serious cardiac dysfunction, left ventricular ejection fraction ≥50%
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Has adequate organ function before registration, defined as: a) Marrow Function: Absolute neutrophil count (ANC) ≥1.2×109 /L, Platelet count ≥100×109 /L, Hemoglobin (Hb) ≥90 g/L b) Hepatic function: Total bilirubin（TBIL≤1.5 ULN, AST and ALT without liver metastasis ≤2.5 ULN, AST and ALT with liver metastasis ≤5.0 ULN
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Coagulation function: international normalized ratio (INR) ≤1.5×ULN, and activated partial thromboplastin time (APTT) ≤1.5 ULN
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Urinary protein ≤2+ or ≤1000mg/24 hours
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For premenopausal women with childbearing potential, a pregnancy test must be taken within 7 days prior to the start of treatment. Serum or urine pregnancy must be negative and must be non-lactating. Adequate barrier contraceptive measures should be taken during the treatment and 6 months after the end of treatment for all subjects (regardless of gender)
Exclusion Criteria:
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Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other anti-tumor therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first administration; mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration; oral fluorouracil-like drugs such as S-1, capecitabine, or palliative radiotherapy within 2 weeks prior to the first administration
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Mixed small-cell lung cancer (SCLC) and NSCLC histology
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Subjects with history of severe heart disease, such as: symptomatic congestive heart failure (CHF) ≥ Grade 2 (CTCAE 5.0), New York Heart Association (NYHA) ≥ Grade 2 heart failure, history of transmural myocardial infarction, unstable angina pectoris etc
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Subjects with prolonged QT interval (QTc >470 msec), complete left bundle branch block, Grade 3 atrioventricular block
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Active autoimmune diseases and inflammatory diseases, such as: systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease and Hashimoto's thyroiditis, etc., except for Type 1 diabetes, hypothyroidism that can be controlled only by alternative treatment, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis)
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Other malignant tumors were diagnosed within 5 years prior to the first administration with the following exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after radical resection
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Subjects with poorly controlled hypertension by two kinds of antihypertensive drugs (systolic blood pressure>150 mmHg or diastolic blood pressure>100 mmHg)
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Subjects have Grade 3 lung disease defined according to NCI-CTCAE v5.0, or a history of interstitial lung disease (ILD
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Unstable thrombotic events such as deep vein thrombosis, arterial thrombosis, and pulmonary embolism requiring therapeutic intervention within the previous 6 months before screening; Infusion set-related thrombosis is excluded
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Symptoms of active central nervous system metastasis. However, subjects with stable brain metastasis can be included. Stable is defined as:
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With or without antiepileptic drugs, the seizure-free state lasts for more than 12 weeks
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There is no need to use glucocorticoids
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Continuous multiple MRI (scanning interval at least 8 weeks) showed a stable state in imaging
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Subjects who have a history of allergies to recombinant humanized antibodies or human mouse chimeric antibodies or any of the components of BL-B01D1
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Subjects have a history of autologous or allogeneic stem cell transplantation
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In the adjuvant (or neoadjuvant) treatment of anthracyclines, the cumulative dose of anthracyclines is> 360 mg/m2
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Known Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active Hepatitis B virus infection (HBV-DNA copy number> the lower limit of detection) or active Hepatitis C virus infection (HCV antibody positive and HCV-RNA > the lower limit of detection)
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Subjects with active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.
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Participated in another clinical trial within 4 weeks prior to participating in the study
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Other conditions that the investigator believes that it is not suitable for participating in this clinical trial
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hematology/Oncology Associates of Treasure Coast | Port Saint Lucie | Florida | United States | 34952 |
| 2 | Prisma Health Cancer Institute | Greenville | South Carolina | United States | 29605 |
Sponsors and Collaborators
- SystImmune Inc.
Investigators
- Study Director: Clinical Leader, SystImmune Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BL-B01D1-LUNG-101