Clinical trial NCT06840821: Evaluating the Safety, Tolerability, and Preliminary Anti-tumor Activity of MB0151 in Adult Subjects With Advanced Solid Tumors Expressing Somatostatin Receptors
Official title: A Phase I/II, Multicenter, Open-label, Single-arm, Dose-escalation and Dose-expansion Study Evaluating the Safety, Tolerability, and Preliminary Anti-tumor Activity of MB0151 Sequential Therapy in Adult Subjects With Advanced Solid Tumors (Including Gastroenteropancreatic Neuroendocrine Neoplasms, Small Cell Lung Cancer or Triple Negative Breast Cancer)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Lead sponsor: Mainline Biosciences (Shanghai) Co., Ltd
Sponsor class: OTHER
First posted: 2025-02-21
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-label, single-arm, dose-escalation and dose-expansion Phase I/II study to evaluate the safety, tolerability and preliminary anti-tumor activity of MB0151 in adult subjects (at least 18 years old) with advanced solid tumors. This study includes two phases: dose escalation and dose expansion. In this study, the protocol of accelerated titration combined with i3+3 is used for dose escalation,administered intravenously every 2 weeks. Enrolled subjects will be sequentially assigned to the planned dose cohorts according to this protocol to receive MB0151 treatment and will be monitored for the occurrence of DLT. The RP2D and/or OBD will be determined by considering the PK profile, safety and efficacy data in the dose-escalation stage (including backfill cohorts).


Eligibility criteria: Inclusion Criteria:

1. Male or female subjects aged ≥18 years.
2. Subjects must have locally advanced or metastatic solid tumors confirmed by histology or cytology, which have failed or are intolerant of standard treatment.
3. ECOG PS is 0-1.
4. Life expectancy ≥3 months.
5. normal organ function, defined as follows:Bone marrow (not treated with blood transfusion or hematopoietic stimulating factor within 14 days): Absolute neutrophil count (ANC)≥1.5×109/L, platelet count ≥100×109/L, hemoglobin ≥ 90 g/L.Liver: total bilirubin (TBIL)≤1.5× upper limit of normal value (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤3×ULN (if accompanied by liver metastasis, ≤5×ULN).Kidney: Serum creatinine concentration ≤1.5×ULN.Coagulation function: activated partial thromboplastin time (APTT) ≤ 1.5× ULN; International normalized ratio (INR) or prothrombin time (PT)≤1.5×ULN.
6. Requirements for the detection of biomarkers: For the dose escalation and backfill cohort in the Phase I study, biomarkers are not detected when they are selected; For phase II study, biomarkers were detected by IHC in the central laboratory at baseline.
7. According to RECIST version 1.1, there is at least one target lesion.
8. Male or female subjects who are infertile, not in pregnancy or agree to use at least one effective contraceptive method during the study intervention period (from 14 days before the first administration to at least 180 days after the last administration of the study intervention).
9. An informed consent form (ICF) that can be understood and signed, including compliance with ICF and the requirements and restrictions listed in this plan.

Exclusion Criteria:

1. According to the researcher's judgment, there are serious or poorly controlled systemic diseases, active bleeding tendency, renal transplantation or liver transplantation, active infection, including syphilis-specific antibody or human immunodeficiency virus (HIV) antibody positive, or active hepatitis B or C.
2. Suffering from other malignant tumors within 3 years before the first administration, except those who have received adequate treatment.
3. Meet one or more of the following cardiac criteria: severe or unstable angina pectoris; Myocardial infarction, coronary artery or peripheral artery bypass grafting, stroke or transient ischemic attack and symptomatic orthostatic hypotension occurred within 6 months before screening; New york Heart Association II-IV heart failure.
4. Undergo major surgery within 28 days before C1D1.
5. Brain metastases with unstable clinical symptoms and/or a history of meningeal diseases, brain stem or spinal cord compression.
6. Have a life-threatening trauma with increased risk of bleeding or a history of severe head trauma or intracranial surgery within 2 months before entering the study group.
7. There is clear imaging evidence of tumor cavity or large blood vessel invasion, and the tumor is adjacent to important blood vessel structures, and the researcher judges that there is a risk of fatal bleeding.
8. Peripheral motor neuropathy or peripheral neuropathy with CTCAE grade ≥2 exists.
9. There are active viral, bacterial or fungal infections with clinical significance.
10. Suffering from inflammatory bowel diseases, including Crohn's disease and ulcerative colitis.
11. Clinically significant lung diseases.
12. suffering from acute or chronic inflammatory skin disease has not yet recovered.
13. Have a history of deep venous thrombosis, pulmonary embolism or other serious venous thromboembolism within 3 months before the first administration.
14. There is pelvic cavity, abdominal cavity, chest cavity or pericardial effusion that needs intervention.
15. The subject has a history of immunodeficiency diseases, including congenital and acquired immunodeficiency diseases.
16. Ophthalmology: There were active ocular surface diseases at baseline (based on ophthalmic evaluation). Have a history of cicatricial conjunctivitis (evaluated by an ophthalmologist).
17. Previous treatment distance Before the first administration of the drug in this study (C1D1): 28 days or 5 half-lives (whichever is shorter), I received systemic anti-tumor treatment.
18. Vaccinated with live attenuated vaccine within 4 weeks before the first administration of the study drug, or expected to need to be vaccinated with live attenuated vaccine during the study period.
19. received a cumulative dose of ≥150 mg or more corticosteroids (prednisone or equivalent dose of corticosteroids) within 2 weeks before the first infusion.
20. Previous treatments with coupled or uncoupled orestatin derivatives, including verbotezumab, verbotezumab, vintoizumab, vidicon, vitexozumab, etc.
21. Any previous AE related to antineoplastic drugs must be restored to Grade ≤1.
22. Participate in other interventional clinical research at the same time, except for observational (non-interventional) research or in the follow-up period of interventional research.
23. known past or current suffering from coagulation defects that lead to increased risk of bleeding.
24. suffering from massive bleeding that has not yet healed.
25. allergic to octreotide or other somatostatin analogues or have a history of allergic reactions; Allergy to the study drug or payload or its derivatives or a history of immediate allergic reaction.
26. Other circumstances that the researcher thinks may cause excessive risks to the subjects, or may adversely affect their participation in this study, and the researcher judges that they are not suitable to participate.

Primary outcomes:
measure: Phase I: Incidence of AEs, SAEs, infusion-related AEs, administration site AEs, AEs with CTCAE Grade ≥ 3 and AEs related to the investigational product
timeFrame: up to 2 years
measure: Phase I: Incidence of DLT, MTD
timeFrame: From the first dose to 28 days
measure: Phase I: ECG QTc Interval
timeFrame: up to 2 years
measure: Phase I: OBD for dose-expansion study
timeFrame: up to 2 years
measure: Phase II: ORR
timeFrame: up to 2 years
measure: Phase II: DOR
timeFrame: up to 2 years
measure: Phase II: DCR
timeFrame: up to 2 years
measure: Phase II: PFS
timeFrame: up to 2 years
measure: Phase II: OS
timeFrame: up to 2 years
Secondary outcomes:
measure: Phase I: Cmax
timeFrame: up to 2 years
measure: Phase I:Tmax
timeFrame: up to 2 years
measure: Phase I: AUC0-t
timeFrame: up to 2 years
measure: Phase I: AUC0-∞
timeFrame: up to 2 years
measure: Phase I: t1/2
timeFrame: up to 2 years
measure: Phase I: CL
timeFrame: up to 2 years
measure: Phase I: Vss
timeFrame: up to 2 years
measure: Phase I: Incidence and severity of adverse events of interest
timeFrame: up to 2 years
measure: Phase I: Anti-drug antibody (ADA) positive rate
timeFrame: up to 2 years
measure: Phase I: Objective Response Rate (ORR)
timeFrame: up to 2 years
measure: Phase I: Duration of Response (DOR)
timeFrame: up to 2 years
measure: Phase I: Disease Control Rate (DCR)
timeFrame: up to 2 years
measure: Phase I: Progression-Free Survival (PFS)
timeFrame: up to 2 years
measure: Phase I: Overall Survival (OS)
timeFrame: up to 2 years
measure: Phase II: Incidence of AEs, SAEs, infusion-related AEs, administration site AEs, AEs with CTCAE Grade ≥ 3 and AEs related to the investigational product
timeFrame: up to 2 years
measure: Phase II: Cmax
timeFrame: up to 2 years
measure: Phase II: Cmin
timeFrame: up to 2 years
measure: Phase II: ADA positive rate
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Jinan
country: China
facility: Cancer Hospital Affiliated to Shandong First Medical University
state: Shandong
Study officials:
References: