Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of BL-M05D1 in Subjects With Solid Tumors

NCT07021066 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BL-M05D1-ST-101
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 17

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.

Conditions

Gastric Adenocarcinoma; Advanced Pancreatic Ductal Adenocarcinoma; Esophageal Adenocarcinoma; Biliary Tract Cancer; Other Solid Tumors

Keywords

CLDN 18.2

Outcome Measures

Primary Outcomes (7)

• Participants with Dose-limiting toxicities

  A DLT is defined as the following: Toxicity that results in a \>14-day delay in treatment \- Hematologic toxicities Grade 4 neutrophil count decreased lasting \>7 days Grade ≥3 febrile neutropenia of any duration Grade ≥3 platelet count decreased with clinically significant hemorrhage Grade 4 thrombocytopenia lasting \>72 hours \- Nonhematologic toxicities Death not clearly related to disease progression or extraneous cause Hy's law cases Grade ≥3 nonhematologic toxicities, except for: Grade 3 nausea/vomiting or diarrhea for less than 72 hours with adequate antiemetic and other supportive care Grade 3 fatigue for less than 1 week Grade ≥3 electrolyte abnormality that lasts up to 72 hours, is not clinically complicated, and resolves spontaneously or responds to conventional medical interventions Grade ≥3 amylase or lipase that is not associated with symptoms or clinical manifestations of pancreatitis

  1 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)

  1 year

• Participants with abnormal physical examination findings

  Measure the number of participants with abnormal physical examination findings.

  1 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)

  1 year

• Participants with abnormal ECG and ECHO/MUGA reading

  Patients with abnormal ECG parameters (including the change from-baseline ECG parameters: heart rate \[HR\]; PR; QTcF; and QRS intervals \[∆HR, ∆PR, ∆QTcF, and ∆QRS\]), and ECHO/MUGA findings

  1 year

• Participants with abnormal lab results

  Measure the number of participants with abnormal clinical laboratory values

  1 year

• 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

  The actual number of subjects enrolled and dose levels to be explored in this study will depend on the MTD and/or RDE based on DLTs reported during the DLT observation period.

  1 year

Secondary Outcomes (18)

• Cmax of BL-M05D1

  1 year

• Cmax of anti-BL-M05D1 antibodies

  1 year

• Cmax of free payload ED-04

  1 year

• Tmax of BL-M05D1

  1 year

• Tmax of anti-BL-M05D1 antibodies

  1 year

Study Arms (1)

Experimental BL-M05D1 administered Day 1 per cycle

EXPERIMENTAL

BL-M05D1 will be administered on Day 1 by intravenous (IV) infusion every 3 weeks

Drug: BL-M05D1

Interventions

BL-M05D1 DRUG

BL-M05D1 will be administered on D1 every 3 weeks.

Experimental BL-M05D1 administered Day 1 per cycle

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed the informed consent form voluntarily and agreed to follow the program requirements
• Age: ≥18 years
• Has a life expectancy of ≥3 months
• Has documented locally advanced or metastatic solid tumor(s) that are known to potentially express CLDN18.2 as defined below that have recurred or progressed on at least 1 line of prior systemic therapy (including adjuvant/neoadjuvant), have no other standard of care options, and have no available curative options, including:
• Gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (AC): Subjects with CLDN18.2, human epidermal growth factor receptor 2 (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.
• Pancreatic ductal AC (PDAC): Subjects may enter screening prior to completing the first line of standard therapy.
• Esophageal AC (EAC): Subjects with HER2, PD-L1 and/or MSI-H/dMMR positive tumors must have received targeted treatment in their prior lines of therapy.
• Biliary tract cancers (BTCs): Subjects with HER2 overexpression, NTRK fusions, KRAS mutations, IDH1 mutations, FGFR2 fusions, BRAF mutations and/or MSI-H/dMMR positive tumors must have received targeted treatment in their prior lines of therapy.
• Other solid tumors not specified above may be included IF they have documented CLDN18.2 expression by IHC (1+). 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.
• Agree to provide most recent existing tumor samples (formalin-fixed paraffin-embedded \[FFPE\] tissue block or slides) from primary or metastatic sites (see details in Section 7.1.1) for tissue-based evaluation of CLDN18.2 expression. A fresh biopsy is required if no archival/FFPE block or slides are available. Re-biopsy is recommended if the subject previously received a CLDN18.2-directed treatment.
• Has at least one measurable lesion based on RECIST (Response Evaluation Criteria in Solid Tumors) v1.1
• Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1
• Toxicity of previous antitumor therapy has returned to Grade ≤1 as defined by the National Cancer Institute (NCI) CTCAE v5.0, except for alopecia and endocrinopathies controlled by replacement therapy that must be Grade ≤2
• Has no serious cardiac dysfunction, left ventricular ejection fraction ≥50%
• Has adequate organ function before enrollment, defined as:

You may not qualify if:

• Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other antitumor therapy within 4 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
• Subjects with history of severe heart disease, such as symptomatic congestive heart failure (CHF) ≥ Grade 2 (CTCAE v5.0), New York Heart Association (NYHA) ≥ Grade 2 heart failure at any time, or history of myocardial infarction or unstable angina pectoris within 6 months before enrollment
• Subjects with prolonged QT interval corrected (\[QTcF\] \>470 msec), complete left bundle branch block, Grade 3 atrioventricular block
• 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. Subjects with well-controlled type 1 diabetes, hypothyroidism, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis) are permitted. For autoimmune conditions that are active but stable and low grade on systemic therapy, discussion with the medical monitor is required prior to screening
• Subjects with other prior malignancies except for: basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after adequate resection, or other malignancy treated with curative intent with a disease-free interval of at least 3 years prior to screening
• Subjects with poorly controlled hypertension by two types of antihypertensive drugs (systolic blood pressure \>150 mmHg or diastolic blood pressure \>100 mmHg)
• Subjects with advanced or clinically significant lung diseases, such as poorly controlled chronic obstructive pulmonary disease and asthma, restrictive lung disease, pulmonary hypertension, etc.
• Subjects who have a history of noninfectious interstitial lung disease (ILD)/ pneumonitis that required treatment with steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
• Subjects with stroke or transient ischemic attack (TIA) within 6 months before enrollment
• Subjects with a thromboembolic event (eg, deep vein thrombosis \[DVT\] or pulmonary embolism \[PE\]) within 6 months before enrollment except for those who are clinically stable and receiving treatment with adequate anticoagulant therapy for at least 3 weeks before enrollment
• 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.
• Subjects with pre-existing Grade ≥2 peripheral neuropathy
• Subjects who have a history of anaphylaxis or severe hypersensitivity to recombinant humanized antibodies or human-mouse chimeric antibodies or any of the components of BL-M05D1
• Subjects who are receiving treatment with systemic glucocorticoids \>10 mg/day equivalent of prednisone, except for the treatment of chronic obstructive pulmonary disease, antiemetic, infusion reactions; however, treatment with low dose glucocorticoids (≤10 mg/day equivalent of prednisone) is permitted. The chronic use of topical, inhaled, and locally injected steroids is permitted
• Subjects who have received treatment with anthracyclines with a cumulative dose exceeding 360 mg/m2

Sponsors & Collaborators

• SystImmune Inc.: lead

Study Sites (17)

Mayo Clinic Cancer Center- Phoenix

Phoenix, Arizona, 85054, United States

RECRUITING

HonorHealth

Scottsdale, Arizona, 85266, United States

RECRUITING

University of Colorado Health

Aurora, Colorado, 80045, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06510, United States

RECRUITING

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

NOT YET RECRUITING

Sarah Cannon Research Institute - Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

NOT YET RECRUITING

NEXT Oncology- Austin

Austin, Texas, 78758, United States

RECRUITING

NEXT Oncology- Dallas

Dallas, Texas, 75039, United States

RECRUITING

MD Anderson

Houston, Texas, 77030, United States

NOT YET RECRUITING

NEXT Oncology San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

START Center for Care Center- San Antonio

San Antonio, Texas, 78229, United States

NOT YET RECRUITING

Baylor Scott and White Medical Center- Temple Clinic

Temple, Texas, 76504, United States

RECRUITING

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Biliary Tract Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Study Officials

• Sarah Tannenbaum

  SystImmune Inc.

  STUDY DIRECTOR

Central Study Contacts

Stephanie Yee

CONTACT

425.453.6841; stephanie.yee@systimmune.com

Whitney Eakins

CONTACT

425.453.6841; whitney.eakins@systimmune.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2025
• First Posted: June 13, 2025
• Study Start: July 30, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (17)