Clinical trial NCT06505824: A Study of BL-M14D1 in Patients With Locally Advanced or Metastatic Small Cell Lung Cancer, Neuroendocrine Tumors and Other Solid Tumors
Official title: A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics Characteristics and Preliminary Efficacy of BL-M14D1 in Patients With Locally Advanced or Metastatic Small Cell Lung Cancer, Neuroendocrine Tumors and Other Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Small Cell Lung Cancer
Neuroendocrine Tumors
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
First posted: 2024-07-17
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is an open, multicenter, dose-escalation and expansion-enrollment nonrandomized phase I clinical study to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of BL-M14D1 in locally advanced or metastatic solid tumors.


Eligibility criteria: Inclusion Criteria:

1. Voluntarily sign the informed consent and follow the requirements of the protocol;
2. No gender limit;
3. Age: ≥18 years old and ≤75 years old (stage Ia); ≥18 years old (stage Ib);
4. Expected survival time ≥3 months;
5. Histologically and/or cytologically confirmed locally advanced or metastatic solid tumors that are incurable or currently have no standard treatment;
6. Consent to provide archival tumor tissue samples or fresh tissue samples from primary or metastatic lesions within 2 years;
7. Must have at least one measurable lesion according to RECIST v1.1 definition;
8. ECOG 0 or 1;
9. Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by NCI-CTCAE v5.0;
10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
11. The level of organ function must meet the requirements on the premise that blood transfusion is not allowed within 14 days before the screening period and no cell growth factor drugs are allowed;
12. Coagulation function: international normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5ULN;
13. The urine protein + 2 or 1000 mg / 24 h or less or less;
14. For premenopausal women with fertility may have to 7 days before beginning treatment for a pregnancy test, serum pregnancy must be negative, and must not be lactating; All enrolled patients (male or female) were advised to use adequate barrier contraception throughout the treatment cycle and for 6 months after the end of treatment.

Exclusion Criteria:

1. Anti-tumor therapy such as chemotherapy or biological therapy has been used within 4 weeks or 5 half-lives before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral drugs such as fluorouracil;
2. Prior receipt of an ADC drug with a TOPI inhibitor as a toxin;
3. History of severe heart disease or cerebrovascular disease;
4. QT prolongation, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;
5. Active autoimmune and inflammatory diseases;
6. Other malignant tumors diagnosed within 5 years before the first dose;
7. Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure \&gt; 150 mmHg or diastolic blood pressure \&gt; 100 mmHg);
8. A history of ILD requiring steroid therapy, or current ILD or grade ≥2 radiation pneumonitis according to the RTOG/EORTC definition, or suspicion of such a condition during screening;
9. Complicated pulmonary diseases leading to clinically severe respiratory function impairment;
10. Patients with massive or symptomatic effusions or poorly controlled effusions;
11. Imaging examination showed that the tumor had invaded or wrapped around the chest, neck, pharynx and other large blood vessels;
12. Unstable thrombotic events requiring therapeutic intervention within 6 months before screening; Infusion-related thrombosis was excluded;
13. Symptoms of active central nervous system metastasis;
14. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any excipients of BL-M14D1;
15. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
16. Anthracycline cumulative dose \> 360 mg/m2 in previous (new) adjuvant therapy;
17. HIV antibody positive, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
18. Active infection requiring systemic therapy with serious infection within 4 weeks before informed consent; There were indications of pulmonary infection or active pulmonary inflammation within 2 weeks before informed consent;
19. Participated in another clinical trial within 4 weeks before the first dose;
20. Pregnant or lactating women;
21. A history of severe neurological or psychiatric illness;
22. Severe unhealed wound, ulcer, or fracture within 4 weeks before signing the informed consent;
23. Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent;
24. History of intestinal obstruction, inflammatory bowel disease, or extensive bowel resection or presence of Crohn's disease, ulcerative colitis, or chronic diarrhea;
25. Patients scheduled for vaccination or receiving live vaccine within 28 days before the first dose;
26. Other conditions for participation in the trial were not considered appropriate by the investigator.

Primary outcomes:
measure: Phase Ia: Dose limiting toxicity (DLT)
timeFrame: Up to 21 days after the first dose
measure: Phase Ia: Maximum tolerated dose (MTD)
timeFrame: Up to 21 days after the first dose
measure: Phase Ib: Recommended Phase II Dose (RP2D)
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 24 months
measure: Cmax
timeFrame: Up to approximately 24 months
measure: Tmax
timeFrame: Up to approximately 24 months
measure: T1/2
timeFrame: Up to approximately 24 months
measure: AUC0-t
timeFrame: Up to approximately 24 months
measure: CL (Clearance)
timeFrame: Up to approximately 24 months
measure: Ctrough
timeFrame: Up to approximately 24 months
measure: ADA (anti-drug antibody)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Objective Response Rate (ORR)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Disease Control Rate (DCR)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Duration of Response (DOR)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
Study officials:
affiliation: Shanghai East Hospital
name: Caicun Zhou
role: PRINCIPAL_INVESTIGATOR
References: