Evaluating BL-M14D1 in Subjects With Locally Advanced or Metastatic Small Cell Lung Cancer and Neuroendocrine Tumors

NCT07080242 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BL-M14D1-ST-101
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 20

Brief Summary

The objective of this study is to evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of BL-M14D1 in Subjects with locally Advanced or Metastatic Small Cell Lung Cancer and Other Neuroendocrine Neoplasms

Conditions

Neuroendocrine Cancer; Metastatic or Locally Advanced Poorly Differentiated Gastroenteropancreatic Neuroendocrine Carcinoma; Metastatic or Locally Advanced Merkel Cell Carcinoma; Locally Advanced or Metastatic Large Cell Neuroendocrine Carcinoma of the Lung; Metastatic or Locally Advanced Extrapulmonary Neuroendocrine Carcinoma; Poorly Differentiated and/or High Grade Neuroendocrine Neoplasms With Evidence of DLL3 Expression; Small Cell Lung Cancer Metastatic or Locally Advanced; Metastatic or Locally Advanced Neuroendocrine Prostate Cancer

Outcome Measures

Primary Outcomes (7)

• Participants with Dose-limiting toxicities

  A DLT is defined as any of the following events: 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 * Nonhematologic toxicities: * Death not 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-M14D1

  1 Year

• Cmax of anti-DLL3 antibodies

  1 Year

• Cmax of free payload ED-04

  1 Year

• Tmax of BL-M14D1

  1 Year

• Tmax of anti-DLL3 antibodies

  1 Year

Study Arms (1)

Experimental BL-M14D1 administered Day 1 per cycle

EXPERIMENTAL

BL-M14D1 will be administered on Day 1 by intravenous (IV) infusion every 3 weeks

Drug: BL-M14D1

Interventions

BL-M14D1 DRUG

BL-M14D1 will be administered on D1 every 3 weeks.

Experimental BL-M14D1 administered Day 1 per cycle

Eligibility Criteria

• Age: 18 Years - 85 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 trial requirements
• Age ≥18 years
• Participant weighs more than 40 kg
• Life expectancy of ≥3 months
• Documented locally advanced or metastatic SCLC, large cell neuroendocrine cancer of the lung (LCNEC), neuroendocrine prostate cancer (NEPC), poorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) or other extrapulmonary neuroendocrine carcinomas (EP-NECs), Merkel cell carcinoma (MCC), or other poorly differentiated and/or high-grade neuroendocrine neoplasms with evidence of DLL3 expression who have failed at least 1 line of standard therapy in the advanced/metastatic setting or are unable to receive standard treatment Notes: For SCLC, the participant must have failed at least 1 line of platinum therapy in the advanced/metastatic setting. No prior topoisomerase inhibitor-based ADC therapy is permitted. In the dose expansion part, Cohort 6 (DLL3-Positive NEN Subgroup): participants will be eligible based on documented positive DLL3 expression.
• Agree to provide archival tumor samples (formalin-fixed paraffin-embedded \[FFPE\] tissue block or 6-12 slides of 5-μm thickness) from primary or metastatic sites:
• In dose escalation and dose finding: archival tissue should be obtained within 2 years or FFPE block from fresh biopsy. If no archival tissue is available, a fresh tissue biopsy is required
• In dose expansion: an FFPE block from fresh biopsy or archival tissue (within 6 months) is required NOTE: If no archival tissue is available and, a fresh tissue biopsy is clinically contraindicated, please consult the sponsor.
• At least one measurable lesion based on RECIST (Response Evaluation Criteria in Solid Tumors) 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 National Cancer Institute (NCI) CTCAE v5.0, except for alopecia and endocrinopathies controlled by replacement therapy
• No serious cardiac dysfunction and left ventricular ejection fraction ≥50%
• Adequate organ function, defined as:
• Marrow function: Absolute neutrophil count (ANC) ≥1.5×10\^9/, platelet count
• ≥100×10\^9/L, hemoglobin (Hb) ≥9.0 g/dL (blood transfusion, platelet transfusion, erythropoietin (EPO), hematopoiesis agents (such as thrombopoietin \[TPO\]), and granulocyte colony-stimulating factor \[G-CSF\] use are not allowed 1 week prior to screening)

You may not qualify if:

• Chemotherapy, biological therapy, immunotherapy, , 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; radical radiotherapy, major surgery within 4 weeks prior to the first administration; mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration; oral fluorouracil drugs such as tegafur, capecitabine, or palliative radiotherapy within 2 weeks prior to initial administration.
• Participants who have received prior topoisomerase inhibitor-based ADC therapy
• Concomitant use of strong inhibitors and inducers of any CYP enzyme or transporter system within 2 weeks prior to the first administration and throughout all parts of the study
• Participants with history of severe heart disease, such as symptomatic (CHF) ≥Grade 2 (CTCAE v5.0), New York Heart Association (NYHA) ≥Grade 2 heart failure at any time, history of myocardial infarction or unstable angina pectoris within 6 months before enrollment
• 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. Participants with skin diseases that do not require systemic treatment (such as vitiligo, psoriasis), well-controlled type 1 diabetes, or hypothyroidism 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.
• Participants with other prior or concurrent 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
• Participants with poorly controlled hypertension by 2 types of antihypertensive drugs (systolic blood pressure \>150 mmHg or diastolic blood pressure \>100 mmHg)
• Participants with advanced/ clinically significant lung diseases, such as poorly controlled chronic obstructive pulmonary disease (COPD) and asthma, restrictive lung disease, pulmonary hypertension etc.
• Participants who have a history of noninfectious ILD/pneumonitis that required treatment with steroids, 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 screening
• Participants with a thromboembolic event (eg, deep vein thrombosis \[DVT\] or pulmonary embolism \[PE\]) within 6 months before screening except for those who are clinically stable and receiving treatment with adequate anticoagulant therapy for at least 3 weeks before screening
• Participants with primary neoplasms in the (CNS), active or untreated CNS metastases 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 radiological evidence of new or enlarging brain metastases and no requirements for corticosteroids 14 days prior to screening.
• Participants with preexisting Grade ≥2 peripheral neuropathy
• Participants 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-M14D1
• Previous organ transplantation or allogeneic hematopoietic stem cell transplantation

Sponsors & Collaborators

• SystImmune Inc.: lead

Study Sites (20)

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

RECRUITING

UCLA

Los Angeles, California, 90095, United States

NOT YET RECRUITING

UCSF- San Francisco (Helen Diller Family Comprehensive Cancer Center)

San Francisco, California, 94158, United States

NOT YET RECRUITING

University of Colorado - Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

NOT YET RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06520-8028, United States

NOT YET RECRUITING

Emory Winship

Atlanta, Georgia, 30322, United States

RECRUITING

University of Kentucky - Markey Cancer Center

Lexington, Kentucky, 40536, United States

NOT YET RECRUITING

John Theurer Cancer Center-Hackensack

Hackensack, New Jersey, 07601, United States

RECRUITING

Rutgers Cancer Institute

New Brunswick, New Jersey, 08901, United States

NOT YET RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

NOT YET RECRUITING

Ohio State University

Columbus, Ohio, 43201, United States

NOT YET RECRUITING

Providence Cancer Institute

Portland, Oregon, 97213, United States

NOT YET RECRUITING

Prisma Health Cancer Institute

Greenville, South Carolina, 29605, United States

NOT YET RECRUITING

NEXT Dallas

Dallas, Texas, 75039, United States

NOT YET RECRUITING

START Dallas- Fort Worth

Dallas, Texas, 76104, United States

NOT YET RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

NEXT Houston

Houston, Texas, 77054, United States

NOT YET RECRUITING

START- San Antonio

San Antonio, Texas, 78229, United States

NOT YET RECRUITING

NEXT Oncology Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

University of Washington/Fred Hutchinson Cancer Center

Seattle, Washington, 98195, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Carcinoma, Neuroendocrine; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Rishi Jain

  SystImmune Inc.

  STUDY DIRECTOR

Central Study Contacts

Lien Huzzy

CONTACT

4254536841; lien.huzzy@systimmune.com

Whitney Eakins

CONTACT

4254536841; 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: July 14, 2025
• First Posted: July 23, 2025
• Study Start: April 28, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (20)