Evaluating the Safety, Tolerability, and Preliminary Anti-tumor Activity of MB0151 in Adult Subjects with Advanced Solid Tumors Expressing Somatostatin Receptors

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). The recommended dose and tumor types for the expansion cohorts will be determined based on the safety and efficacy outcomes of subjects treated in the Phase I dose-escalation study. In each expansion cohort, approximately 30 subjects will receive MB0151 treatment for up to 6 cycles by IV infusion on D1 and D15 of each cycle . When the subject has completed a total of 6 cycles (24 weeks) of treatment, if he/she is judged by the investigator to show clinical benefit and signs the ICF (for expansion period), and does not meet the stopping criteria, MB0151 treatment can be continued unless disease progression criteria are met, intolerable toxicity occurs or informed consent is withdrawn (whichever occurs first).


Eligibility Criteria:
Inclusion Criteria：

1. The subjects must be either 18 years old or the legal age of consent in the jurisdiction where the study is conducted at the time they sign the ICF.
2. Subjects must have a histologically or cytologically confirmed solid tumor in one of the following categories: Advanced or recurrent SCLC, progressed after previous standard treatment, or Low-grade, medium-grade or high-grade advanced GEP-NET, progressed after prior first-line or multiple lines of anti-cancer therapy (unless no standard treatment is available or such treatment is deemed unsuitable), or Metastatic or locally advanced unresectable, histologically confirmed TNBC, characterized by the absence of expression of human epidermal growth factor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR), recurrent/refractory after standard treatment or without standard treatment available (must include paclitaxel chemotherapy).
3. ECOG PS of 0-1.
4. Life expectancy ≥ 3 months.
5. Normal organ function within 28 days before C1D1, defined as follows: Bone marrow (without transfusion or treatment with hematopoietic stimulating factors within 14 days): absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, haemoglobin ≥ 90 g/L. Liver: total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN), or TBIL \> 1.5 × ULN with direct bilirubin (DBIL) ≤ ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN (if accompanied by metastases to liver, ≤ 5 × ULN). Kidneys: If the serum creatinine concentration is ≥ 1.5 × ULN, the estimated creatinine clearance must be ≥ 50 mL/min (Cockcroft-Gault formula) ; Coagulation: Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; international normalized ratio (INR) ≤ 1.5 × ULN.
6. The requirements for SSTR expression level are different, as follows: For the dose-escalation main cohort (MC) in Phase I study, there is no requirement for SSTR expression level at enrollment, but archived or fresh tumor tissue will be collected; during the study, based on clinical data obtained, the SSTR expression level in subjects in subsequent dose-escalation main cohort may be added as an additional inclusion criterion; For the backfill cohort (BC) in Phase I and Phase II studies, archived or fresh tumor tissues will be collected. Additionally, GEP-NET and SCLC patients are required to have their SSTR expression levels assessed at baseline.
7. The results of the last imaging examination within 28 days prior to C1D1 indicate the presence of at least one measurable lesion assessed according to RECIST v1.1.
8. Male subjects are eligible to participate in the study if they agree to comply with the following during the study intervention period and until at least 180 days after the last dose of study intervention: Avoid donating fresh uncleaned sperm. Additionally: Avoid preference for customary heterosexual intercourse (long-term, continuous abstinence) and agree to remain abstinent. Or Use male condoms, and the female partner uses another highly effective contraceptive method with an annual failure rate of less than 1%, as described in Section 11.4 (Appendix 4). Men of childbearing potential are advised to consider collecting semen specimens for storage in case of future conception.
9. Female subjects are eligible for study participation if they are not pregnant or breastfeeding and meet at least one of the following conditions: The subject is a woman of non-childbearing potential (WONCBP), The investigator should assess the possibility of contraceptive method failure (e.g., non-compliance, recent initiation) considering the first administration of the investigational drug. The results of a blood pregnancy test conducted within 72 h before the first administration of the investigational drug in WOCBP must be negative (see Section 8.2.23). Additional requirements for pregnancy test during and after study intervention are described in Section 8.2.23. The investigator is responsible for reviewing medical history, menstrual history and recent sexual activity to reduce the risk of enrollment of women with undetected early pregnancy.
10. Capable of providing signed ICF as described in Appendix 1, including adherence to the requirements and restrictions listed in the ICF and this protocol.

Eligibility Criteria：

1. Severe or poorly controlled systemic diseases, active haemorrhagic diathesis, renal transplant or liver transplant, active infections, including syphilis-specific antibody or human immunodeficiency virus (HIV) antibody positive, or active hepatitis B (hepatitis B surface antigen positive and HBV-DNA above the upper limit of the reference value) or hepatitis C (hepatitis C virus antibody positive), as judged by the investigator.
2. Subjects with other malignant tumors in the past 3 years, except those who have been adequately treated.
3. Meeting one or more of the following cardiac criteria: Unstable angina pectoris;Myocardial infarction within 6 months prior to screening;New York Heart Association heart failure class II-IV ;QT interval (QTc) corrected using Fredericia's formula at baseline: male \> 450 msec and female \> 470 msec; Clinically significant cardiac rhythm, conduction or morphological abnormalities (e.g., complete left bundle branch block, third-degree AV block) on resting ECG; Congenital long QT syndrome; Symptomatic orthostatic hypotension within 6 months prior to screening; Hypertension that cannot be well controlled after the use of antihypertensive therapy (i.e., systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg); Stroke or transient ischemic attack within 6 months prior to screening.
4. Receive major surgery within 28 days prior to C1D1.
5. Have a history of leptomeningeal disease or spinal cord compression.
6. Have brain metastases with unstable clinical symptoms (excluding those without clinical symptoms, or those whose symptoms are stable and do not require hormone therapy).
7. Trauma that increased the risk of life-threatening bleeding within 2 months prior to enrollment, or a history of severe head trauma or intracranial surgery.
8. Radiographic evidence of cavernous pulmonary lesions.
9. Peripheral motor neuropathy or peripheral neuropathy with CTCAE grade ≥ 2.
10. There is a clinically significant active viral, bacterial, or fungal infection.
11. Inflammatory bowel disease, including Crohn's disease and Colitis ulcerative.
12. Inflammation pulmonary disease, including moderate and severe asthma requiring long-term drug therapy and chronic obstructive pulmonary disease (COPD).
13. Acute or chronic inflammatory dermatosis that has not healed.
14. Ophthalmology: Active ocular surface disease at baseline (based on ophthalmic evaluation);History of cicatrizing conjunctivitis (as evaluated by an ophthalmologist).
15. Anti-tumor therapy within 28 days prior to C1D1, including chemotherapy, radiotherapy (excluding stereotactic radiosurgery or SBRT for brain metastasis), biological therapy, targeted therapy, immunotherapy, etc. Within 6 weeks after receiving treatment with mitomycin C and nitrosoureas (such as carmustine \[BiCNU or BCNU\] and lomustine); Within 2 weeks after receiving oral fluorouracil (FU), small molecule targeted anti-tumor drugs and endocrine therapy; Within 5 half-lives of the drug (whichever is longer); Within 2 weeks after receiving traditional Chinese medicine treatment for anti-tumor indications; Within 4 weeks after receiving clinical anti-tumor therapy.
16. Vaccination with a live attenuated vaccine within 4 weeks prior to the first dose of study drug or anticipation that such a live attenuated vaccine will be required during the study.
17. Received granulocyte colony-stimulating factor (G-CSF) or granulocyte/macrophage colony-stimulating factor support treatment within 1 week prior to the screening visit, or received pegylated G-CSF treatment within 2 weeks prior to the screening visit.
18. Received treatment with a cumulative dose of ≥ 150 mg of corticosteroids (prednisone or an equivalent dose of corticosteroids) within 2 weeks before the first infusion.
19. Previously received treatment with auristatin derivatives, both conjugated and unconjugated, including brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, disitamab vedotin, and tisotumab vedotin.
20. Subjects who have not recovered from symptomatic side effects of radiotherapy or symptoms of autoimmune toxicity associated with prior checkpoint inhibitors at the initiation of screening procedures.
21. Use of strong CYP3A inhibitors and inducers within 14 days or 5 × t1/2 (whichever is shorter) prior to the first dose of investigational drug.
22. Any prior investigational anti-tumor drug-related AEs must have recovered to ≤ Grade 1, excluding alopecia, endocrine disorders/vitiligo/haemoglobin (Hb) ≥ 90 g/L, or Grade 2 neurotoxicity (excluding peripheral and sensory neuropathy) due to prior therapy, unless the investigator believes these symptoms are not expected to pose an excessive risk to the subjects or adversely affect their participation in this study.
23. Known history or current coagulopathy contributing to increased risk of haemorrhage.
24. Haemorrhage that has not recovered, defined as: Symptomatic haemorrhage in organs of critical regions, such as intracranial, intraocular, retroperitoneal, intra-articular or intrapericardial, or intramuscular haemorrhage with compartment syndrome; Haemorrhage leading to a decrease in haemoglobin level of ≥ 20 g/dL (0.31 mmol/L) or haemorrhage leading to transfusion of ≥ 2 units of whole blood or red blood cells within 14 days before C1D1.
25. Subjects who are allergic or have a history of anaphylactic reaction to octreotide or other somatostatin analog; subjects who are allergic or have a history of anaphylaxis to payload or its derivatives.
26. Any other condition which, in the opinion of the investigator, may pose undue risk to the subjects or may adversely affect the participation of subjects in this study.