Study to Evaluate BL-B01D1 in Patients With Metastatic or Unresectable Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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A Phase 1 Study Evaluating the Safety, Tolerability, and Efficacy of BL-B01D1 in Subjects With Metastatic or Unresectable Non-Small Cell Lung Cancer

Conditions
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Non Small Cell Lung Cancer, NSCLC, Lung Cancer

Intervention / Treatment
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* Drug: BL-B01D1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign informed consent Age: ≥18 years Expected survival > or = 3months 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. Agree to provide a tumor sample Has at least one measurable lesion based on RECIST 1.1 Has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1 Exclusion Criteria: Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery, targeted therapy and other anti-tumor therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first administration Mixed small-cell lung cancer (SCLC) and NSCLC histology Subjects with history of severe heart disease Active autoimmune diseases and inflammatory diseases Other malignant tumors were diagnosed within 5 years Subjects with poorly controlled hypertension Subjects have Grade 3 lung disease or a history of interstitial lung disease Unstable thrombotic events such as deep vein thrombosis, arterial thrombosis, and pulmonary embolism requiring therapeutic intervention within the previous 6 months before screening Symptoms of active central nervous system metastasis. Subjects who have a history of allergies to recombinant humanized antibodies or human mouse chimeric antibodies or any of the components of BL-B01D1 Subjects have a history of autologous or allogeneic stem cell transplantation Known HIV, active tuberculosis, active Hepatitis B virus infection or active Hepatitis C virus infection Subjects with active infections requiring systemic treatment Participated in another clinical trial within 4 weeks prior to participating in the study Other conditions that the investigator believes that it is not suitable for participating in this clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BL-B01D1 administered Day 1 and Day 8 per cycle<br>BL-B01D1 will be administered on Day 1 and Day 8 by intravenous infusion every 3 weeks | Drug: BL-B01D1<br>* The study includes 3 parts: Part 1 Dose escalation. Part 2 Dose Finding non-randomized and Part 3 Dose expansion randomized.<br>|
| Experimental: BL-B01D1 administered Day 1 per cycle<br>BL-B01D1 will be administered on Day 1 via by intravenous infusion every 3 weeks | Drug: BL-B01D1<br>* The study includes 3 parts: Part 1 Dose escalation. Part 2 Dose Finding non-randomized and Part 3 Dose expansion randomized.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants with Dose-limiting toxicities | 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, | One year | 
| Participants with Serious Adverse Events (SAEs) and treatment-emergent adverse events (TEAEs), | Measuring the number of patients with serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs) | One year | 
| Participants with abnormal physical examination findings | Measure the number of participants with abnormal physical examination findings. | One year | 
| Participants with ability to care for themselves, daily activity, and physical activity | 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) | One year | 
| Participants with abnormal ECG reading | Measure the number of participants with abnormal ECG parameters | One year | 
| Participants with abnormal lab results | Measure the number of participants with abnormal clinical laboratory values | One year | 
| 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 | 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. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of BL-B01D1 | Calculate maximum (peak) observed concentration of BL-B01D1 | One year | 
| Cmax of anti-EGFR×HER3 antibody | Calculate maximum (peak) observed concentration of anti-EGFR×HER3 antibody | One year | 
| Cmax of free payload ED-04 | Calculate maximum (peak) observed concentration of free payload ED-04 | One year | 
| Tmax of BL-B01D1 | Calculate time of maximum observed concentration of BL-B01D1 | One year | 
| Tmax of anti-EGFR×HER3 antibody | Calculate time of maximum observed concentration of anti-EGFR×HER3 antibody | One year | 
| Tmax of free payload ED-04 | Calculate time of maximum observed concentration of free payload ED-04 | One year | 
| AUC(0-8) of BL-B01D1 | Calculate area under the serum concentration-time curve of BL-B01D1 from time 0 to 8 hours | One year | 
| AUC(0-8) of anti-EGFR×HER3 antibodies | Calculate area under the serum concentration-time curve of anti-EGFR×HER3 antibodies from time 0 to 8 hours | One year | 
| AUC(0-8) of free payload ED-04 | Calculate area under the serum concentration-time curve of free payload ED-04 from time 0 to 8 hours | One year | 
| AUC(last) of BL-B01D1 | Calculate area under the serum concentration-time curve up of BL-B01D1 to the last quantifiable time | One year | 
| AUC(last) anti-EGFR×HER3 antibodies | Calculate area under the serum concentration-time curve up of anti-EGFR×HER3 antibodies to the last quantifiable time | One year | 
| AUC(last) of free payload ED-04 | Calculate area under the serum concentration-time curve up of free payload ED-04 to the last quantifiable time | One year | 
| Overall Response Rate (ORR) | To assess the clinical efficacy of BL-B01D1 as measured by ORR using RECIST criteria v 1.1 | One year | 
| Disease Control Rate (DCR) | To assess the clinical efficacy of BL-B01D1 as measured by DCR using RECIST criteria v 1.1 | One year | 
| Time To Response (TTR) | To assess the clinical efficacy of BL-B01D1 as measured by TTR using RECIST criteria v 1.1 | One year | 
| Progression-Free Survival (PFS), | To assess the clinical efficacy of BL-B01D1 as measured by PFS using RECIST criteria v 1.1 | One year | 
| Overall Survival (OS). | To assess the clinical efficacy of BL-B01D1 as measured by OS using RECIST criteria v 1.1 | One year |