Clinical trial NCT05983432: Evaluate BL-B01D1 in Patients With Metastatic or Unresectable Non-Small Cell Lung Cancer (NSCLC) and Other Solid Tumors
Official title: A Phase 1 Study Evaluating the Safety, Tolerability, and Efficacy of BL-B01D1 in Subjects With Metastatic or Unresectable Non-Small Cell Lung Cancer and Other Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Non Small Cell Lung Cancer
Lung Cancer
Breast Cancer
Esophageal Cancer
Small Cell Lung Cancer
Nasopharyngeal Cancer
Head and Neck Squamous Cell Carcinoma
Lead sponsor: SystImmune Inc.
Sponsor class: INDUSTRY
First posted: 2023-08-09
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria:

1) Signed the informed consent voluntarily and agreed to follow the program requirements 2) Either sex 3) Age: ≥18 years 4) Has a life expectancy of ≥3 months 5) Has histologically documented, incurable, locally advanced or metastatic epithelial origin malignant cancer, priority to include the following tumor types: NSCLC, HER2 - breast cancer, esophageal cancer, SCLC, NPC, and HNSCC 6) Agree to provide archived tumor samples (tissue block or slides) from primary or metastatic sites within 2 years. In the event that no archival tissue is available a fresh tissue biopsy is highly encouraged but not mandatory.

7) Has at least one measurable lesion based on RECIST V1.1 8) Has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1 9) 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.) 10) Has no serious cardiac dysfunction, left ventricular ejection fraction ≥50% 11) 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 c) Renal function: Creatinine clearance ≥50 mL/min (According to the Cockcroft and Gault equation) 12) Coagulation function: international normalized ratio (INR) ≤1.5×ULN, and activated partial thromboplastin time (APTT) ≤1.5 ULN 13) Urinary protein ≤2+ or ≤1000mg/24 hours 14) Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception during the course of the study and for 7 months for females and 4 months for males after the last dose of study treatment. An additional contraceptive method, such as a barrier method like a condom is required.

15) Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and must be nonlactating. Female subjects are considered WOCBP unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \>45 years old in the absence of other biological or physiological causes. In addition, females \<55 years old must have a serum follicle stimulating hormone (fsh) level \> 40 mIU/mL to confirm menopause.

16) For subjects with NSCLC:

a) Evidence of documented EGFR TKI-sensitizing deletion mutation in EGFR Exon 19 (ex19del) or leucin-arginine substitution point mutation in EGFR Exon 21 (ex21L858R), the serine-isoleucine mutation in EGFR Exon 20 (ex20S768I), the leucine-glutamine substitution mutation in Exon 21 (ex21L861Q), or the glycine substitution (with alanine, cysteine, or serine) mutation in Exon 18 (ex18G719X) at or after the time of disease diagnosis and prior to initiation of treatment.

17) For Triple-Negative Breast Cancer (TNBC, HER2-/HR-):

a) Histologically or cytologically confirmed and documented locally advanced, recurrent inoperable or metastatic TNBC

Exclusion criteria:

1. Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other anti-tumor therapy within 2 weeks or 5 half-lives (whichever is shorter) prior to the first administration; major surgery within 4 weeks prior to the first administration; mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration
2. 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;
3. Subjects with prolonged QT interval (QTc \>470 msec), complete left bundle branch block, Grade 3 atrioventricular block
4. 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 I diabetes, hypothyroidism that can be controlled only by standard of care treatment, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis)
5. 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
6. Subjects with poorly controlled hypertension by two kinds of antihypertensive drugs (systolic blood pressure\>150 mmHg or diastolic blood pressure\>100 mmHg)
7. Subjects have Grade 3 lung disease defined according to NCI-CTCAE v5.0, a history of interstitial lung disease (ILD)/ pneumonitis
8. 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
9. Patients with primary tumors in the central nervous system (CNS) and active or untreated CNS metastases and/or carcinomatous meningitis should be excluded. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks and have no evidence of new or enlarging brain metastases and no requirements for corticosteroids 14 days prior to dosing with the investigational product (IP). Patients on low dose corticosteroids (\<20 mg prednisone or equivalent/day) may participate.
10. Subjects who have a history of allergies to recombinant humanized antibodies or human-mouse chimeric antibodies or any of the components of BL-B01D1
11. Subjects have a history of autologous or allogeneic stem cell transplantation (Allo-HSCT)
12. Has received treatment with anthracyclines with a cumulative dose exceeding 360 mg/m2
13. Subjects with ≥ Grade 2 hypokalemia (low concentration of potassium in the blood) according to CTCAE v5.0 (Grade 1: subject asymptomatic with potassium levels \<LLN - 3.0 mmol/L or equivalent)
14. 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)
15. Subjects with active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis.
16. Received an investigational drug within 4 weeks, or two half-lives (whichever is longer) prior to first dose of study treatment
17. Subjects who are pregnant or breastfeeding
18. Other conditions that the investigator believes may make the subject not suitable for participating in this clinical trial.
19. For subjects with NSCLC:

    1. Prior therapy with any ADC targeting EGFR and/or HER3 or containing a topoisomerase 1 inhibitor payload
    2. Participants treated with more than two systemic chemotherapies prior to randomization. NOTE: Progression of disease within 12 months after receiving neoadjuvant and adjuvant chemotherapies is considered 1 prior systemic chemotherapy
    3. Previously documented EGFR Exon 20 insertion mutations as primary EGFR mutations
20. For Triple-Negative Breast Cancer (TNBC, HER2-/HR-):

    1. Prior therapy with any ADC targeting EGFR and/or HER3 or containing a topoisomerase 1 inhibitor payload Note: For TNBC dose expansion cohort, if few subjects without prior ADC therapy targeting HER3 and EGFR or with a topo I inhibitor can be enrolled, then subjects with prior ADCs with these targets or payload may be enrolled upon consultation with the sponsor
    2. Participants treated with more than two systemic chemotherapies prior to randomization. NOTE: Progression of disease within 12 months after receiving neoadjuvant and adjuvant chemotherapies is considered 1 prior systemic chemotherapy

Primary outcomes:
measure: Participants with Dose-limiting toxicities
timeFrame: One year
measure: Participants with Serious Adverse Events (SAEs) and treatment-emergent adverse events (TEAEs),
timeFrame: One year
measure: Participants with abnormal physical examination findings
timeFrame: One year
measure: Participants with ability to care for themselves, daily activity, and physical activity
timeFrame: One year
measure: Participants with abnormal ECG reading
timeFrame: One year
measure: Participants with abnormal lab results
timeFrame: One year
measure: 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
timeFrame: One year
Secondary outcomes:
measure: Cmax of BL-B01D1
timeFrame: One year
measure: Cmax of anti-EGFR×HER3 antibody
timeFrame: One year
measure: Cmax of free payload ED-04
timeFrame: One year
measure: Tmax of BL-B01D1
timeFrame: One year
measure: Tmax of anti-EGFR×HER3 antibody
timeFrame: One year
measure: Tmax of free payload ED-04
timeFrame: One year
measure: AUC(0-8) of BL-B01D1
timeFrame: One year
measure: AUC(0-8) of anti-EGFR×HER3 antibodies
timeFrame: One year
measure: AUC(0-8) of free payload ED-04
timeFrame: One year
measure: AUC(last) of BL-B01D1
timeFrame: One year
measure: AUC(last) anti-EGFR×HER3 antibodies
timeFrame: One year
measure: AUC(last) of free payload ED-04
timeFrame: One year
measure: Overall Response Rate (ORR)
timeFrame: One year
measure: Disease Control Rate (DCR)
timeFrame: One year
measure: Time To Response (TTR)
timeFrame: One year
measure: Progression-Free Survival (PFS),
timeFrame: One year
measure: Overall Survival (OS).
timeFrame: One year
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Duarte
country: United States
facility: City of Hope Cancer Center
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: Santa Monica
country: United States
facility: UCLA Santa Monica
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: New Haven
country: United States
facility: Yale University, Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Orlando
country: United States
facility: Sara Cannon Research Institute Lake Nona
state: Florida
city: Port Saint Lucie
country: United States
facility: Hematology - Oncology Associates of the Treasure Coast
state: Florida
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Head Neck Services
state: New York
city: Greenville
country: United States
facility: PRISMA Health/ITOR
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon - Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: Oncology Consultants, P.A.
state: Texas
city: Houston
country: United States
facility: University of Texas M.D. Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: University of Washington Fred Hutchinson
state: Washington
Study officials:
affiliation: SystImmune Inc.
name: Jimmy Zhao, MD, PhD
role: STUDY_DIRECTOR
References: