Gastric AdenocarcinomaPhase 1NCT07021066
Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of BL-M05D1 in Subjects With Solid Tumors
A Phase 1 study testing BL-M05D1 in people with Gastric Adenocarcinoma and Advanced Pancreatic Ductal Adenocarcinoma, run by SystImmune Inc. at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastric Adenocarcinoma, Advanced Pancreatic Ductal Adenocarcinoma, Esophageal Adenocarcinoma
- What is being tested?
- BL-M05D1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 11 sitesUnited States
- Study dates
- 30 Jul 2025to 31 May 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed the informed consent form voluntarily and agreed to follow the program requirements.
- Age ≥18 years.
- Life expectancy of ≥3 months.
- Dose Escalation and Dose Finding (Parts 1 and 2): 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 (refer to Section 6.3.1), have no other standard of care options, and have no available curative options, including the following:
- Gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (AC): Participants with CLDN18.2, 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): Participants who have received at least 1 line of standard therapy.
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- Esophageal AC (EAC): Participants 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): Participants 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, participants with HER2 and/or PD-L1 positive tumors must have received targeted treatment in their prior lines of therapy, and participants 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 participant previously received a CLDN18.2-directed treatment.
- At least 1 measurable lesion based on RECIST v1.1.
- 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.
- Exceptions: Alopecia and endocrinopathies controlled by replacement therapy must be Grade ≤2.
- No serious cardiac dysfunction, left ventricular ejection fraction ≥50%.
- Adequate organ function before enrollment, defined as follows:
- Marrow function: absolute neutrophil count (ANC) ≥1.5×109/L, platelet (PLT) count ≥100×109/L, hemoglobin (Hb) ≥9.0 g/dL (blood transfusion, platelet transfusion, erythropoietin (EPO), hematopoiesis agents, and G-CSF use are not allowed 1 week prior to screening).
- Hepatic function: total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN) (≤3 × ULN for participants with Gilbert's syndrome or liver metastasis at baseline); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) without liver metastasis ≤3.0 × ULN; AST and ALT with liver metastasis ≤5.0 × ULN.
- Note: For participants with Gilbert's syndrome, conjugated bilirubin ≤1.5 × ULN and TBIL <3.0 × ULN in the absence of liver metastases.
- Renal function: creatinine clearance (CrCl) ≥60 mL/min (Cockcroft-Gault equation) or estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73 m2 (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] creatinine equation).
- Coagulation parameters: International normalized ratio (INR) ≤1.5 × ULN, and activated partial thromboplastin time (aPTT) ≤1.5 × ULN, unless receiving anticoagulation therapy with prothrombin time and aPTT levels within the intended therapeutic range.
- Sexually active fertile participants and their partners must agree to use highly effective methods of contraception (defined in Section 17.5 [Appendix E]) during the course of the study and after the last dose of study treatment (7 months for women and 4 months for men). An additional contraceptive method, such as a barrier method (eg, condom), is recommended.
- Individuals of childbearing potential (IOCBP) must have a negative serum pregnancy test at screening and must be nonlactating. Female participants are considered IOCBP 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.
- Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff.
- All participants must be willing to receive prophylactic G-CSF during their time on study (see Section 6.3.4.5).
- Additional Inclusion Criteria for Dose Optimization (Part 3)
- PDAC Expansion Arm: Participants who have received at least 1 line of standard therapy and no more than 2 lines of systemic therapy (refer to Section 6.3.1).
- Note: Participants who have received prior treatment with a CLDN18.2-directed treatment must be able and willing to provide tissue sample obtained following treatment with anti-CLDN18.2 agent.
- Basket Expansion Arm: 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 in the advanced or metastatic setting (refer to Section 6.3.1).
- G/GEJ AC: Participants with CLDN18.2, HER2, PD-L1, and/or MSI-H/dMMR positive tumors must have received targeted treatment in their prior lines of therapy.
- G/GEJ AC and BTCs: Participants who have received prior treatment with an anti-CLDN18.2 antibody must be able and willing to provide tissue sample obtained following treatment with anti-CLDN18.2 agent.
- BTCs: Participants 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.
Who cannot join
- Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, targeted therapy (including small-molecule inhibitor of tyrosine kinase), or other antitumor therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first administration of study drug; major surgery within 4 weeks prior to the first administration; mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration.
- Participants 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.
- Participants 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, or Hashimoto's thyroiditis..
- Exception: Participants with skin diseases that do not require systemic treatment (such as vitiligo, psoriasis); well-controlled type 1 diabetes; or hypothyroidism are permitted.
- Note: For autoimmune conditions that are active but stable, low grade, and on systemic therapy, discussion with the medical monitor is required prior to screening.
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- Participants with other prior malignancies.
- Exceptions: 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.
- Participants with advanced or clinically significant lung diseases such as poorly controlled chronic obstructive pulmonary disease (COPD) or asthma, restrictive lung disease, or pulmonary hypertension.
- Participants who have a history of noninfectious interstitial lung disease (ILD)/pneumonitis that required treatment with steroids or have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- Participants with stroke or transient ischemic attack (TIA) within 6 months before enrollment.
- Participants with a thromboembolic event (eg, deep vein thrombosis, pulmonary embolism) within 6 months before enrollment.
- Exception: Those who are clinically stable and receiving treatment with adequate anticoagulant therapy for at least 3 weeks before enrollment may participate.
- Participants with primary tumors in the central nervous system (CNS), or active or untreated CNS metastases and/or carcinomatous meningitis.
- Exception: Participants with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks, have no evidence of new or enlarging brain metastases, and have no requirements for corticosteroids 14 days prior to dosing with the IP. Participants on low-dose corticosteroids (<10 mg prednisone or equivalent/day) may participate.
- Participants with pre-existing Grade ≥2 peripheral neuropathy.
- Participants who have a history of anaphylaxis or severe hypersensitivity to recombinant humanized antibodies, human-mouse chimeric antibodies, or any of the components of BL-M05D1.
- Participants who are receiving treatment with systemic glucocorticoids >10 mg/day equivalent of prednisone.
- Exceptions:
- Treatment of COPD and infusion-related reactions (IRRs) is permitted.
- Treatment with low-dose glucocorticoids (≤10 mg/day equivalent of prednisone), including antiemetics, is permitted.
- The chronic use of topical, inhaled, and locally injected steroids is permitted.
- Participants with known or suspected human immunodeficiency virus (HIV) infection (HIV antibody positive).
- Exceptions: Participants are allowed to participate if all the following criteria are met:
- undetectable HIV RNA and CD4 count ≥350 cells/μL at screening;
- no acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 12 months prior to screening; and
- on stable antiretroviral therapy (ART) for at least 4 weeks prior to enrollment, with projected continuation of ART as clinically indicated while on the study.
- Participants with known active hepatitis B virus (HBV) infection (positive hepatitis B surface antigen [HBsAg] test).
- Exceptions: Participants with a chronic inactive HBV infection are eligible if all the following criteria are met:
- HBV DNA viral load <500 IU/mL;
- normal AST and ALT, or if liver metastasis is present, AST and ALT <3 × ULN that are not attributed to HBV infection; and
- on antiviral treatment as clinically indicated.
- Participants with known active hepatitis C virus (HCV) infection (HCV antibody positive and HCV-RNA > the lower limit of detection).
- Exception: Participants with a positive anti-HCV antibody are eligible only if quantitative polymerase chain reaction (qPCR) is negative for HCV-RNA.
- Participants with known active tuberculosis.
- Participants with active infections that require IV antibiotic, antiviral, or antifungal treatment, such as severe pneumonia, bacteremia, or sepsis, within 1 week prior to first dose of study treatment.
- Exception: Participants on stable oral antimicrobials with no clinical or laboratory evidence of active infection are eligible.
- Participants who are pregnant, breastfeeding, or planning to become pregnant during the study.
- Other conditions that the investigator or sponsor believes are not suitable for participating in this clinical trial.
- For Dose Optimization Only: Prior treatment with any topoisomerase inhibitor ADC.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
University of Michigan
Ann Arbor, Michigan, 48109
University of Colorado Health
Aurora, Colorado, 80045
NEXT Oncology- Austin
Austin, Texas, 78758
NEXT Oncology- Dallas
Dallas, Texas, 75039
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Valkyrie Clinical Trials
Los Angeles, California, 90067
Sarah Cannon Research Institute - Oncology Partners
Nashville, Tennessee, 37203
Yale Cancer Center
New Haven, Connecticut, 06510
Ochsner Medical Center
New Orleans, Louisiana, 70121
NEXT Oncology San Antonio
San Antonio, Texas, 78229
HonorHealth
Scottsdale, Arizona, 85266
About this study
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
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.
Read the detailed description
This is a multicenter Phase 1, open-label study to evaluate the safety, tolerability, pharmacokinetic profile, and initial efficacy of BL-M05D1 in subjects with unresectable locally advanced or metastatic solid tumors that are known to potentially express CLDN18.2, including but not limited to gastric and gastroesophageal junction adenocarcinoma (G/GEJ AC), esophageal AC (EAC), pancreatic ductal AC (PDAC), and biliary tract cancer (BTC). Participants must 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.
This study will be conducted in three parts (dose escalation, dose finding and dose expansion). Subjects will be dosed on Day 1 of a continuous 21-day treatment cycle.
- Conditions
- Gastric Adenocarcinoma, Advanced Pancreatic Ductal Adenocarcinoma, Esophageal Adenocarcinoma, Biliary Tract Cancer, Other Solid Tumors
- Being tested
- BL-M05D1
- Keywords
- CLDN 18.2
- Medical subject headings
- Adenocarcinoma Of Esophagus, Biliary Tract Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BL-M05D1Drug
BL-M05D1 will be administered on D1 every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Experimental BL-M05D1 administered Day 1 per cycle | Experimental | BL-M05D1 will be administered on Day 1 by intravenous (IV) infusion every 3 weeks Receives: Drug: BL-M05D1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Measured: 1 year
Participants with abnormal physical examination findings
Measure the number of participants with abnormal physical examination findings.
Measured: 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)
Measured: 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
Measured: 1 year
Participants with abnormal lab results
Measure the number of participants with abnormal clinical laboratory values
Measured: 1 year
To determine the maximum tolerated dose (MTD) if reached or minimum safe and pharmacologically effective dose (MSED).
The actual number of subjects enrolled and dose levels to be explored in this study will depend on the MTD and/or MSED based on DLTs reported during the DLT observation period.
Measured: 1 year
Secondary outcomes (18)
Cmax of BL-M05D1
Calculate maximum (peak) observed concentration of BL-M05D1
Measured: 1 year
Cmax of anti-BL-M05D1 antibodies
Calculate maximum (peak) observed concentration of anti-BL-M05D1 antibodies
Measured: 1 year
Cmax of free payload ED-04
Calculate maximum (peak) observed concentration of free payload ED-04
Measured: 1 year
Tmax of BL-M05D1
Calculate time of maximum observed concentration of BL-M05D1
Measured: 1 year
Tmax of anti-BL-M05D1 antibodies
Calculate time of maximum observed concentration of anti-BL-M05D1 antibodies
Measured: 1 year
Tmax of free payload ED-04
Calculate time of maximum observed concentration of free payload ED-04
Measured: 1 year
AUC(0-8) of BL-M05D1
Calculate area under the serum concentration-time curve of BL-M05D1 from time 0 to 8 hours
Measured: 1 year
AUC(0-8) of anti-BL-M05D1 antibodies
Calculate area under the serum concentration-time curve of anti-BL-M05D1 antibodies from time 0 to 8 hours
Measured: 1 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
Measured: 1 year
AUC(last) of BL-M05D1
Calculate area under the serum concentration-time curve up of BL-M05D1 to the last quantifiable time0 to 8 hours
Measured: 1 year
AUC(last) of anti-BL-M05D1 antibodies
Calculate area under the serum concentration-time curve up of anti-BL-M05D1 antibodies to the last quantifiable time0 to 8 hours
Measured: 1 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
Measured: 1 year
Overall Response Rate (ORR)
To assess the clinical efficacy of BL-M05D1 as measured by ORR using RECIST criteria v 1.1
Measured: 1 year
Disease Control Rate (DCR)
To assess the clinical efficacy of BL-M05D1 as measured by DCR using RECIST criteria v 1.1
Measured: 1 year
Time To Response (TTR)
To assess the clinical efficacy of BL-M05D1 as measured by TTR using RECIST criteria v 1.1
Measured: 1 year
Progression-Free Survival (PFS)
To assess the clinical efficacy of BL-M05D1 as measured by PFS using RECIST criteria v 1.1
Measured: 1 year
Overall Survival (OS)
To assess the clinical efficacy of BL-M05D1 as measured by OS using RECIST criteria v 1.1
Measured: 1 year
Duration of response (DoR)
To assess the clinical efficacy of BL-M05D1 as measured by DoR using RECIST criteria v 1.1
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2025
- Study start30 Jul 2025
- Primary completion28 Feb 2027 (estimated)
- Study completion31 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastric AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- BOIN
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- SystImmune Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sarah Tannenbaum, Study director, SystImmune Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07021066
- Sponsor's protocol ID
- BL-M05D1-ST-101
- Status last verified
- Aug 2026
- First submitted
- 23 May 2025
- Last updated
- 5 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No