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

Phase 1

Recruiting

• Conditions: Small Cell Lung Cancer; NSCLC; Lung Cancer; NPC; Non Small Cell Lung Cancer; Esophageal Cancer; Nasopharyngeal Cancer; Breast Cancer; SCLC
• Interventions: Drug: BL-B01D1

• Registration Number: NCT05983432
• Lead Sponsor: SystImmune Inc.

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) and Other Solid Tumors.

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 and Other Solid Tumors.

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 Timeline

• Study First Submitted: 2023-07-12
• Study First Submitted QC: 2023-08-01
• Study Start: 2023-08-08
• Study First Posted: 2023-08-09
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-19
• Last Update Posted: 2024-07-22
• Primary Completion: 2025-12-31
• Study Completion: 2028-03-21

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 260

Inclusion Criteria

1. Sign informed consent
2. Expected survival > or = 3months
3. Has histologically documented, incurable, locally advanced or metastatic epithelial origin malignant cancer, priority to include the following tumor types: Non-Small Cell Lung Cancer, HER2- breast cancer, esophageal cancer, Small Cell Lung Cancer, and Nasopharyngeal Cancer
4. Agree to provide a tumor sample
5. Has at least one measurable lesion based on RECIST 1.1
6. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1
7. 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 or plasma 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.)
8. Has no serious cardiac dysfunction, left ventricular ejection fraction ≥50%.
9. Has adequate organ function before registration
10. Coagulation function: international normalized ratio (INR) ≤1.5×ULN, and activated partial thromboplastin time (APTT) ≤1.5 ULN
11. Urinary protein ≤2+ or ≤1000mg/24 hours
12. 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
13. Must agree to use adequate barrier contraceptive measures during the treatment and 6 months after the end of treatment for all subjects (regardless of gender)

Exclusion Criteria

1. 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
2. Subjects with history of severe heart disease
3. Active autoimmune diseases and inflammatory diseases
4. Other malignant tumors were diagnosed within 5 years
5. Subjects with poorly controlled hypertension
6. Subjects have Grade 3 lung disease or a history of interstitial lung disease
7. Unstable thrombotic events such as deep vein thrombosis, arterial thrombosis, and pulmonary embolism requiring therapeutic intervention within the previous 6 months before screening
8. Symptoms of active central nervous system metastasis
9. Subjects who have a history of allergies to recombinant humanized antibodies or human mouse chimeric antibodies or any of the components of BL-B01D1
10. Subjects have a history of autologous or allogeneic stem cell transplantation
11. Known HIV, active tuberculosis, active Hepatitis B virus infection or active Hepatitis C virus infection
12. Subjects with active infections requiring systemic treatment
13. Participated in another clinical trial within 4 weeks prior to participating in the study
14. Other conditions that the investigator believes that it is not suitable for participating in this clinical trial
15. Subjects with prolonged QT interval (QTc >470 msec), complete left bundle branch block, Grade 3 atrioventricular block
16. Has received treatment with anthracyclines with a cumulative dose exceeding 360 mg/m2

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
BL-B01D1 administered Day 1 and Day 8 per cycle	BL-B01D1	BL-B01D1 will be administered on Day 1 and Day 8 by intravenous infusion every 3 weeks
BL-B01D1 administered Day 1 per cycle	BL-B01D1	BL-B01D1 will be administered on Day 1 via by intravenous infusion every 3 weeks

Primary Outcome Measures

Name	Time	Method
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 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.
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 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

Secondary Outcome Measures

Name	Time	Method
Tmax of BL-B01D1	One year	Calculate time of maximum observed concentration of BL-B01D1
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
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
Disease Control Rate (DCR)	One year	To assess the clinical efficacy of BL-B01D1 as measured by DCR using RECIST criteria v 1.1
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
Cmax of free payload ED-04	One year	Calculate maximum (peak) observed concentration of free payload ED-04
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
Progression-Free Survival (PFS),	One year	To assess the clinical efficacy of BL-B01D1 as measured by PFS using RECIST criteria v 1.1
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
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(last) of BL-B01D1	One year	Calculate area under the serum concentration-time curve up of BL-B01D1 to the last quantifiable time
Time To Response (TTR)	One year	To assess the clinical efficacy of BL-B01D1 as measured by TTR using RECIST criteria v 1.1
Overall Response Rate (ORR)	One year	To assess the clinical efficacy of BL-B01D1 as measured by ORR 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

Trial Locations

Locations (2)

SystImmune Recruiting Center; 🇺🇸 Houston, Texas, United States

SystImmune Recruiting Site; 🇪🇸 Madrid, Spain