Locally Advanced Extrapulmonary Neuroendocrine Carcinoma, Locally Advanced Large Cell Neuroendocrine Carcinoma of the Lung, Locally Advanced Merkel Cell Carcinoma, Locally Advanced Neuroendocrine Prostate Cancer, Locally Advanced Poorly Differentiated Gastroenteropancreatic Neuroendocrine, Metastatic Advanced Merkel Cell Carcinoma, Metastatic Advanced Poorly Differentiated Gastroenteropancreatic Neuroendocrine Carcinoma, Metastatic Large Cell Neuroendocrine Carcinoma of the Lung, Metastatic Neuroendocrine Prostate Cancer, Neuroendocrine Cancer, Small Cell Lung Cancer Metastatic or Locally Advanced
Conditions
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
Detailed description
A Phase 1 Open-Label Study 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
Interventions
DRUGBL-M14D1
BL-M14D1 will be administered on D1 every 3 weeks.
Sponsors
SystImmune Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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. * 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
Exclusion criteria
* 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 * 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 advanced/ clinically significant lung diseases, such as poorly controlled chronic obstructive pulmonary disease (COPD) and asthma, restrictive lung disease, pulmonary hypertension etc. * Participants with primary neoplasms in the central nervous system (CNS), active or untreated CNS metastases, spinal cord compression, or carcinomatous meningitis should be excluded. Active brain metastases are defined as untreated symptomatic brain metastases or untreated brain metastases requiring systemic corticosteroids and/or anticonvulsants to control CNS-related symptoms. Patients with brain metastases are eligible if they meet any of the following criteria: 1. untreated, asymptomatic brain metastases 2. previously treated brain metastases may participate provided they are clinically stable with local therapy (eg, surgery or radiotherapy, currently asymptomatic, no longer requiring corticosteroid treatment, and recovered from all local therapy-related adverse events, as determined by the investigator * Participated in another clinical trial within 4 weeks prior to first dose of study treatment * Participants who are pregnant or 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess safety and tolerability of BL-M14D1 | 18 months | SAEs, AESIs, TEAEs, death, TEAEs leading to discontinuation, DLTs, physical examination findings (including ECOG PS), vital sign measurements, standard clinical laboratory parameters, ECG parameters (including the change-from-baseline ECG parameters), and ECHO/MUGA findings |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To characterize the PK of BL M14D1, total anti-DLL3 antibody, and payload (Ed-04) | 18 months | PK Endpoints: Serum concentration of BL-M14D1, total anti-DLL3 antibody, and free payload ED-04 vs time will be utilized, serum PK parameters will include Cmax, Tmax, AUC0-8, AUClast and, if possible, Kel, t1/2, CL, Vz, Vss of BL-M14D1, total anti-DLL-3 antibody, and Ed-04. These PK parameters will be calculated both after the first dose and after multiple doses if applicable. |
| To investigate the antitumor activity of BL-M14D1 | 18 months | * Tumor response evaluated using RECIST v1.1, ORR, DCR, DoR, TTR, and PFS * OS |
Countries
United States
Contacts
CONTACTLien Huzzy
CONTACTWhitney Eakins
STUDY_DIRECTORJunliang Cai
SystImmune Inc.
Outcome results
None listed