Clinical trial NCT07021066: Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of BL-M05D1 in Subjects With Solid Tumors
Official title: A Phase 1 Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of BL-M05D1 in Subjects With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Gastric Adenocarcinoma
Advanced Pancreatic Ductal Adenocarcinoma
Esophageal Adenocarcinoma
Mucinous Ovarian Adenocarcinoma
Other Solid Tumors
Lead sponsor: SystImmune Inc.
Sponsor class: INDUSTRY
First posted: 2025-06-13
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of BL-M05D1 in Subjects with Advanced or Metastatic Solid Tumors.

Detailed description: This is a multicenter Phase 1, open-label study to evaluate the safety, tolerability, pharmacokinetic profile, and initial efficacy of BLM05D1 in subjects with unresectable locally advanced or metastatic solid tumors of the digestive system and other solid tumors who have received at least 2 lines of standard therapy, including adjuvant/neoadjuvant treatment, or whose cancer is considered refractory to the standard of care or for which no standard treatment is available.

This study will be conducted in three parts (dose escalation, dose finding and dose expansion). Subjects will be dosed on Day 1 on a continuous 21-day treatment cycle.

Eligibility criteria: Inclusion Criteria:

1. Signed the informed consent voluntarily and agreed to follow the program requirements
2. Age: ≥18 years
3. Has a life expectancy of ≥3 months
4. Has documented locally advanced or metastatic solid tumor(s) with radiographic progression on the latest line of therapy, not amenable to curative surgery or radiation, including:

   1. Cohort 1 (Parts 1 to 3): Subjects with gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (AC) who have received at least 2 lines of standard therapy, including adjuvant/neoadjuvant treatment, or whose cancer is considered refractory to standard of care or for which no standard treatment is available.

      Subjects with HER2, PD-L1 and/or microsatellite instability high (MSI-H)/ mismatch repair deficiency (dMMR) positive tumors must have received targeted treatment in their prior lines of therapy.
   2. Cohort 2 (Parts 1 to 3): Subjects with advanced pancreatic ductal AC (PDAC) who have received at least one line of standard therapy. Subjects may enter screening prior to completing the first line of standard therapy.
   3. Cohort 3 (Parts 1 to 2 only): Subjects with esophageal AC (EAC) who have received at least 2 lines of standard therapy, including adjuvant/neoadjuvant treatment, or whose cancer is considered refractory to standard of care or for which no standard treatment is available. Subjects with HER2, PD-L1 and/or MSI-H/dMMR positive tumors must have received targeted treatment in their prior lines of therapy.
   4. Cohort 4 (Parts 1 to 2 only): Subjects with primary mucinous ovarian AC (MOAC) or metastatic MOAC originating in the upper gastrointestinal tract who have received at least 2 lines of standard therapy, including adjuvant/neoadjuvant treatment, or whose cancer is considered refractory to standard of care or for which no standard treatment is available.
   5. Cohort 5 (Parts 1 to 2 only): Subjects with other solid tumors (OT) who have received at least 2 lines of standard therapy, including adjuvant/neoadjuvant treatment, or whose cancer is considered refractory to standard of care or for which no standard treatment is available. As applicable per standard of care, subjects with HER2 and/or PD-L1 positive tumors must have received targeted treatment in their prior lines of therapy, and subjects with MSI-H or dMMR positive tumors must have received immune checkpoint inhibitor.
5. Agree to provide existing tumor samples (formalin-fixed paraffin-embedded \[FFPE\] tissue block or slides) from primary or metastatic sites obtained within 2 years or FFPE block from fresh biopsy (see details in Section 7.1) for tissue-based evaluation of CLDN18.2 expression
6. Has at least one measurable lesion based on RECIST (Response Evaluation Criteria in Solid Tumors) V1.1
7. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1
8. Toxicity of previous antitumor therapy has returned to Grade ≤1 as defined by NCI CTCAE V5.0, except for alopecia and endocrinopathies controlled by replacement therapy that must be Grade ≤2
9. Has no serious cardiac dysfunction, left ventricular ejection fraction ≥50%
10. Has adequate organ function before enrollment, defined as:

    1. Marrow function: Absolute neutrophil count (ANC) ≥1.2×109/L, platelet count (PLT) ≥100×109/L, hemoglobin (Hb) ≥90 g/L
    2. 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
    3. Renal function: Creatinine clearance ≥60 mL/min (Cockcroft-Gault equation)
11. Coagulation parameters: International normalized ratio (INR) ≤1.5×ULN, and activated partial thromboplastin time (APTT) ≤1.5 ULN
12. Urine protein ≤2+ or ≤1000 mg/24 hours
13. Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception (defined in Appendix E) during the course of the study and for 7 months after the last dose of study treatment. An additional contraceptive method, such as a barrier method (eg, condom), is recommended.
14. 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.

Exclusion Criteria:

1. Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other antitumor therapy within 2 weeks or 5 half-lives (whichever is longer) 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 (QTcF \>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 1 diabetes, hypothyroidism that can be controlled by standard of care treatment, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis)
5. Subjects with other prior or concurrent malignant tumors diagnosed within 5 years prior to the first administration considered to be in remission, with the following exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after radical resection, or other malignancy in which treatment does not interfere with the safety or efficacy assessment of the investigational product
6. Subjects with poorly controlled hypertension by two types of antihypertensive drugs (systolic blood pressure \>150 mmHg or diastolic blood pressure \>100 mmHg)
7. Subjects who have Grade 3 lung disease defined according to NCI CTCAE v5.0, or a history of interstitial lung disease (ILD)
8. Subjects with stroke (including transient ischemic attack \[TIA\]), myocardial infarction, or other ischemic event or thromboembolic event (eg, deep vein thrombosis, pulmonary embolism \[DVT/PE\]) within 6 months before randomization except for those with a diagnosis of DVT who are stable and receiving treatment with adequate anticoagulant therapy for at least 3 weeks before randomization
9. Subjects 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 with pre-existing ≥Grade 2 peripheral neuropathy
11. Subjects who have a history of allergies to recombinant humanized antibodies or human-mouse chimeric antibodies or any of the components of BL-M05D1
12. Subjects who have received treatment with anthracyclines with a cumulative dose exceeding 360 mg/m2
13. 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)
14. Subjects with active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc., that require use of intravenous antibiotics, antiviral drugs, or antifungal drugs during the study period.
15. Participated in another clinical trial within 4 weeks or two half-lives (whichever is longer) prior to first dose of study treatment
16. Subjects who are pregnant or breastfeeding
17. Other conditions that the investigator believes are not suitable for participating in this clinical trial.

Primary outcomes:
measure: Participants with Dose-limiting toxicities
timeFrame: 1 year
measure: Participants with Serious Adverse Events (SAEs) and treatment-emergent adverse events (TEAEs)
timeFrame: 1 year
measure: Participants with abnormal physical examination findings
timeFrame: 1 year
measure: Participants with ability to care for themselves, daily activity, and physical activity
timeFrame: 1 year
measure: Participants with abnormal ECG and ECHO/MUGA reading
timeFrame: 1 year
measure: Participants with abnormal lab results
timeFrame: 1 year
measure: To determine the maximum tolerated dose (MTD) if reached or maximum administered dose (MAD) and two or more recommended doses for expansion (RDEs) of BL-M05D1 in metastatic or unresectable tumors
timeFrame: 1 year
Secondary outcomes:
measure: Cmax of BL-M05D1
timeFrame: 1 year
measure: Cmax of anti-BL-M05D1 antibodies
timeFrame: 1 year
measure: Cmax of free payload ED-04
timeFrame: 1 year
measure: Tmax of BL-M05D1
timeFrame: 1 year
measure: Tmax of anti-BL-M05D1 antibodies
timeFrame: 1 year
measure: Tmax of free payload ED-04
timeFrame: 1 year
measure: AUC(0-8) of BL-M05D1
timeFrame: 1 year
measure: AUC(0-8) of anti-BL-M05D1 antibodies
timeFrame: 1 year
measure: AUC(0-8) of free payload ED-04
timeFrame: 1 year
measure: AUC(last) of BL-M05D1
timeFrame: 1 year
measure: AUC(last) of anti-BL-M05D1 antibodies
timeFrame: 1 year
measure: AUC(last) of free payload ED-04
timeFrame: 1 year
measure: Overall Response Rate (ORR)
timeFrame: 1 year
measure: Disease Control Rate (DCR)
timeFrame: 1 year
measure: Time To Response (TTR)
timeFrame: 1 year
measure: Progression-Free Survival (PFS)
timeFrame: 1 year
measure: Overall Survival (OS)
timeFrame: 1 year
measure: Duration of response (DoR)
timeFrame: 1 year
Other outcomes:
Locations:
Study officials:
affiliation: SystImmune Inc.
name: Sarah Tannenbaum
role: STUDY_DIRECTOR
References: