Study of BM230 in Patients With Advanced Solid Tumors

Inclusion Criteria:

Common inclusion criteria (Phase Ia and Phase Ib) (Criteria 1 to 9)

Patients must satisfy all the following criteria to be included in the study:

1. Informed of the study before the start of the study and voluntarily sign their nameand date on the informed consent form (ICF)

2. Males and Females≥18 years old（at the time consent is obtained）

3. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1

4. Life expectancy of ≥ 3 months

5. Adequate organ and bone marrow function, defined as:

• Bone marrow function: hemoglobin ≥ 90 g/L (have not received blood transfusionor erythropoietin treatment within 14 days before the first dose); absoluteneutrophil count ≥ 1.5×109/L (have not received granulocyte colony-stimulatingfactor or granulocyte-macrophage colony-stimulating factor treatment within 14days before the first dose); platelet count ≥ 100×109/L ((have not receivedplatelet transfusion, thrombopoietin, or interleukin-11 treatment within 14days before the first dose)

• Coagulation function: activated partial thromboplastin time and internationalnormalized ratio ≤ 1.5 × ULN

• Liver function (based on the normal range in the sites): TBIL ≤ 1.5 × ULN if nodemonstrable liver lesion(s) (primary or metastases) , or ≤ 3 × ULN in thepresence of liver lesion(s); ALT and AST ≤ 3 × ULN if no demonstrable liverlesion(s) (primary or metastases), or ≤ 5 × ULN in the presence of liverlesion(s)

• Renal function (based on the normal range in the sites): blood creatinine ≤ 1.5 × ULN, or creatinine clearance (CrCl) calculated by the Cockcroft-Gault formula ≥ 50 mL/min, or 24-h urine CrCl ≥ 50 mL/min

• Cardiac function: LVEF ≥ 50%;

6. Female patients of childbearing potential must agree to use a highly effective formof contraception and not donate, or retrieve for their own use, ova from the time ofscreening and throughout the study period, and for at least 6 months after the lastdose of study drug; a negative pregnancy test must be obtained within 7 days beforethe first dose. Male patients must agree to use a highly effective form ofcontraception and not freeze or donate sperm from the time of screening andthroughout the study period, and for at least 6 months after the last dose of studydrug

7. Able and willing to comply with protocol visits and procedures

8. Have HER2 expression (IHC 1+, 2+, or 3+) determined by immunohistochemistry, or HER2amplification (NGS report indicating HER2 amplification) or (for NSCLC) HER2 exon 8,exon 19, or exon 20 mutations

9. Willing to provide archived or fresh tumor tissue samples. Patients who are unableto provide tumor samples or have insufficient samples may be eligible on acase-by-case basis after discussion with the sponsor Additional inclusion criteria for Phase Ia (Criteria 10 to 11)

10. Pathologically confirmed diagnosis of locally advanced or metastatic solid tumors (BC, GC, CRC, and NSCLC are preferable), for which prior standard treatment hadproven to be ineffective or intolerable, or no standard treatment is available, orthe patient refuses standard treatment

11. Have at least one evaluable tumor target lesion according to RECIST version 1.1.Patients in the accelerated titration cohort are not required for the abovementioned evaluable tumor target lesion Additional inclusion criteria for Phase 1b (Criteria 12 to 13)

12. For BC patients:

• Have a pathologically documented advanced/unresectable or metastatic BC

• Have disease progression on or after the last treatment or intolerance to thelast treatment, or for which no standard treatment is available For GC patients:

• Have a pathologically documented advanced/unresectable or metastatic gastric orgastroesophageal junction adenocarcinoma

• Have disease progression on or after prior treatment with at least one line ofPD-(L)1 inhibitors and/or chemotherapy under metastatic setting For CRC patients:

• Have a pathologically documented advanced/unresectable or metastatic CRC

• Have disease progression on or after the last treatment or intolerance to thelast treatment, or for which no standard treatment is available For NSCLC patients:

• Have a pathologically documented Stage IIIB, IIIC, or IV squamous ornon-squamous NSCLC

• Have disease progression on or after prior anti-PD-(L)1 treatment andplatinum-based chemotherapy

13. At least one evaluable tumor target lesion according to RECIST version 1.1

Exclusion Criteria:

Patients who meet any of the following criteria will NOT be included in the study:

Common exclusion criteria (Phase Ia and Ib) (Criteria 1 to 19)

1. Preexisting autoimmune disease (except for patients with vitiligo) needing treatmentwith systemic immunosuppressive therapy for more than 28 days within the last 3years, or clinically relevant immuno-deficiency diseases (eg, agammaglobulinemia orcongenital immunodeficiency)

2. Multiple primary malignancies within 3 years, except adequately resectednon-melanoma skin cancer, curatively treated in situ disease, or other curativelytreated solid tumors (including but not limited to adequately treated thyroidcancer, carcinoma in situ of the cervix, basal or squamous cell skin cancer, orductal carcinoma in situ of the breast treated with curative surgery)

3. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or in the follow-up period of an interventionalstudy

4. In-sufficient washout period of the prior anticancer treatment before the first doseof the investigational product, defined as follows:

• Anti-neoplastic treatments such as chemotherapy, biological therapy, ndimmunotherapy within 3 weeks before the first dose

• Radiotherapy for tumors within 2 weeks before the first dose

• Endocrine therapy for tumors within 2 weeks before the first dose

• Chinese herbal medicine or traditional Chinese medicine for tumor indicationswithin 2 weeks before the first dose

• Other investigational drugs or treatments within 4 weeks before the first dose (fluorouracil and small-molecule targeted drugs should be within 2 weeks beforethe first use of the investigational drugs or within 5 half-lives of the drug,whichever is shorter)

5. Undergone major surgery (not including diagnostic surgery) within 4 weeks before thefirst dose or are expected to undergo major surgery during the study

6. Undergone stem cell transplant or organ transplant

7. Received systemic corticosteroids (defined as > 10 mg/day of prednisone orequivalent) or other immuno-suppressive therapy within 2 weeks before the firstdose. The following are exceptions to this criterion:

• Intranasal, inhaled, topical steroids, topical corticosteroids or local steroidinjections (eg, intra-articular injections)

• Systemic steroids at physiological doses as replacement therapy (eg,physiological corticosteroid replacement therapy for adrenal or pituitaryinsufficiency)

• Steroids as premedication for hypersensitivity reactions (eg, CT scanpremedication)

8. Received any live vaccines within 4 weeks before the first dose or intend to receivelive vaccines during the study

9. A history of leptomeningeal carcinomatosis; or existence of unstable central nervoussystem (CNS) metastases. Stability is defined as having undergone surgical resectionand/or radiation therapy for CNS metastases at least 28 days before the first dose,and meeting all of the following criteria after completion of treatment:

• No neurological symptoms, or symptoms are stable and ≤ grade 1

• No progression of treated lesions and no new lesions within 28 days before thefirst dose by enhanced CT or magnetic resonance imaging (MRI) scan

• Mild brain oedema on imaging during screening, but not requiring systemiccorticosteroids or anti-convulsant drugs

10. Uncontrolled or clinically significant cardiovascular diseases, including but notlimited to:

• History of symptomatic CHF (New York Heart Association [NYHA] class II-IV) orany arterial embolism events (eg, myocardial infarction, unstable angina,cerebrovascular accident, and transient ischaemic attack) within 6 monthsbefore the first dose

• Uncontrolled hypertension, defined as systolic blood pressure (SBP) >160 mmHgand/or diastolic blood pressure (DBP) >100 mmHg after antihypertensivetreatment

• Serious cardiac arrhythmia requiring treatment

• The QT interval corrected by the Fridericia formula (QTcF) is prolonged to > 470 ms

11. Active haemorrhage with significant clinical significance

12. Uncontrolled third-space fluid (eg, pleural effusions, ascites, pericardialeffusions) that requires repeated drainage

13. Uncontrolled or unstable systemic diseases, including diabetes mellitus, hepaticcirrhosis, interstitial lung disease, and obstructive lung disease, by theinvestigator's discretion

14. Uncontrolled infection that requires systemic therapy within 1 week before the firstdose

15. Active hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiencyvirus (HIV), or syphilis infection. Active HBV is defined as hepatitis B coreantibody (HBcAb) or hepatitis B surface antigen (HBsAg) positive, and HBV DNA levelabove ULN at the study site; active HCV is defined as positive hepatitis C antibodyand HCV RNA level above ULN at the site; active HIV is defined as positive HIVantibody; active syphilis is defined as positive Treponema pallidum lab test

16. Unresolved toxicities from previous anticancer therapy, defined as toxicities notyet resolved to NCI CTCAE Grade ≤1, baseline, or the level specified in theinclusion/exclusion criteria with the exception of alopecia (any grade),pigmentation (any grade), and peripheral neuropathy (Grade ≤2). Patients withirreversible toxicity (eg, hearing loss) that is reasonably not expected to beaggravated by the study drug can be enrolled after discussion with the sponsor

17. A history of severe hypersensitivity reactions to the drug substances, inactiveingredients in the drug product, or other mAbs

18. Women who are breastfeeding or pregnant as confirmed by pregnancy tests performedwithin 7 days before the first dose

19. Any illness, medical condition, organ system dysfunction, or social situation,including but not limited to mental illness or substance/alcohol abuse, deemed bythe investigator to be likely to interfere with a patient's ability to sign informedconsent, adversely affect the patient's ability to cooperate and participate in thestudy, or compromise the interpretation of study results