Study of MHB088C in Participants With Advanced or Metastatic Solid Tumors

Inclusion Criteria:

• Participants enrolled must meet all of the following criteria: General conditions

1. Participants voluntarily agree to participate in the study and sign the InformedConsent Form.
2. Aged ≥18years, without gender limitation.
3. Has an Eastern Cooperative Oncology Group Performance score (ECOG) 0 ~ 1.
4. Has a life expectancy of ≥ 3 months.
5. Eligible participants of childbearing potential (males and females) must agree to takehighly reliable contraceptive measures (hormone or barrier method, or absoluteabstinence, etc.) with their partners during the study and within at least 90 daysafter the last dose and agree not to retrieve, freeze or donate sperm or ova fromscreening to at least 3 months after the last dose of investigational drug; femaleparticipants of childbearing potential must have a negative results of blood pregnancytest within 7 days before the first dose of investigational drug, and must benon-lactating.
6. Understand study requirements, willing and able to comply with study and follow-upprocedures. Neoplasm-related criteria
7. Part one: Histologically or cytologically confirmed unresectable advanced ormetastatic malignant solid tumors, that is progressed or intolerant with standard ofcare (SOC), or for which no SOC regimens are available;
8. Part two: Histologically or cytologically confirmed unresectable advanced ormetastatic malignant solid tumors, that is relapsed or progressed following systemictreatment or no standard of care is available, including but not limited to thefollowing types: non-small cell lung cancer (NSCLC); small cell lung cancer (SCLC);esophageal squamous cell carcinoma (ESCC); castration-resistant prostate cancer (CRPC); melanoma (MEL); colorectal cancer (CRC); pancreatic ductal adenocarcinoma (PDAC); head and neck squamous cell carcinoma (HNSCC); hepatocellular carcinoma (HCC);ovarian cancer (OC); endometrial cancer (EC); thyroid cancer (TC); and sarcoma (SARC).
9. Additional inclusion criteria for participants with NSCLC: Histologically or cytologically documented unresectable advanced or metastaticNSCLC and previous progressed during or after systematic treatment withplatinum-contained doublet regimens chemotherapy and immune-checkpoint inhibitors (ICIs); refractory, intolerant or not suitable to the target therapy as perinvestigator discretion for participants with driver gene mutation.
10. Additional inclusion criteria for participants with SCLC: Histologically or cytologically documented unresectable advanced or metastaticSCLC and previous progressed during or after ≥1 lines of systematic treatmentwith platinum-based, doublet regimens chemotherapy and ICIs.
11. Additional inclusion criteria for participants with ESCC: Histologically or cytologically documented unresectable advanced or metastaticESCC previous progressed during or after≥1 line platinum-based of systemictreatment.
12. Additional inclusion criteria for participants with CRPC: Histologically or cytologically documented CRPC without neuroendocrinedifferentiation or small cell elements; Underwent surgical or medical castration,with testosterone levels below 50 ng/dL; Objective progression as determined byradiographic after androgen deprivation therapy; Relapsed or progressed during orafter at least one of the following medicines: abiraterone, enzalutamide,apalutamide, or darolutamide; Relapsed or progressed during or after≥ 1 line ofdocetaxel/mitoxantrone-based cytotoxic chemotherapy regimens for metastatic CRPC;With at least 1 documented lesion confirmed by either a bone scan or a CT/MRIscan.
13. Additional inclusion criteria for participants with MEL: Histologically or cytologically documented unresectable advanced or metastaticMEL and previous progressed during or after ≥1 line of systemic therapy includingICIs
14. Additional inclusion criteria for participants with CRC: Histologically or cytologically documented unresectable advanced or metastaticCRC and previous progressed during or after systematic chemotherapy containingoxaliplatin, irinotecan, fluorouracil and immunotherapy (for participants withMSI-H/dMMR).
15. Additional inclusion criteria for participants with PDAC: Histologically or cytologically documented unresectable advanced or metastaticPDAC and previous progressed during or after ≥ 1 line of systemic therapy inneoadjuvant, adjuvant, locally advanced or metastatic setting.
16. Additional inclusion criteria for participants with HNSCC: Histologically or cytologically documented unresectable advanced or metastaticHNSCC and previous progressed during or after ≥ 1 line of systemic therapy,including platinum-based chemotherapy and ICIs (combined or sequential therapy).
17. Additional inclusion criteria for participants with HCC: Histologically or cytologically documented unresectable advanced or metastaticHCC and previously progressed during or after ≥ 1 line of systemic therapy,including anti-vascular therapy and/or ICI therapy.
18. Additional inclusion criteria for participants with OC: Histologically or cytologically documented unresectable advanced or metastatic OCincluding less-common histology per National Comprehensive Cancer Network (NCCN)of epithelial ovarian cancer as well as fallopian tube cancer and primaryperitoneal cancer and have relapsed or progressed during or after ≥ 1 line ofplatinum-based systemic chemotherapy treatment.
19. Additional inclusion criteria for participants with EC: Histologically or cytologically documented unresectable advanced or metastatic ECand recurrence after radical therapy, and previously treated and progressedduring or after ≥ 1 line of standard systemic therapy.
20. Additional inclusion criteria for participants with TC: Histologically or cytologically documented unresectable advanced or metastatic TCand previous progressed during or after ≥ 1 line of systemic therapy includingplatinum-based chemotherapy or targeted therapy.
21. Additional inclusion criteria for participants with SARC: Histologically or cytologically documented unresectable advanced or metastatic SARCand previous progressed during or after ≥ 1 prior line of systemic therapy includingdoxorubicin-based chemotherapy.
22. Agree to provide the pre-existing diagnostic tumor samples for retrospective testingof target expression and other biomarkers (participants who agree but are unable toprovide pre-existing tumor sample may also be enrolled). There is no minimum targetexpression level required for inclusion.
23. Has at least one measurable tumor lesion as per RECIST v1.1(generally, previouslyirradiated areas or locoregionally treated sites will not be considered as measurablelesions, unless these lesions have clearly progressed or still exist three monthsafter radiotherapy); for participants with CRPC, evaluable lesions as defined by PCWG3criteria or at least one measurable soft tissue tumor lesion as per RECIST v1.1 arerequired. Adequate bone marrow reserve and organ functions:
24. Adequate bone marrow reserve (without transfusion or colony-stimulating factor orequivalent within7 days before the screening period testing); Absolute neutrophilcount (ANC) ≥ 1.5 × 10^9/L; Platelet count ≥ 100 × 10^9/L; Hemoglobin ≥ 9.0 g/dL.
25. Adequate hepatic function (with reference to normal values specified by the clinicalstudy site): Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); TBIL ≤ 2 × ULN ifGilbert's syndrome is present; TBIL ≤ 3.0 × ULN is permitted if direct bilirubin (DBIL) suggests extrahepatic obstruction. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) shall be ≤ 3 × ULNwith non-hepatic tumors and without hepatic metastasis; AST and ALT shall be ≤ 5.0 ×ULN with hepatic tumors or hepatic metastasis;
26. Adequate renal function (with reference to normal values specified by the clinicalstudy site): Creatinine (Cr) ≤ 1.5 × ULN; when Cr > 1.5 × ULN, only participants with creatinineclearance (Ccr) ≥ 50 mL/min can be enrolled (using Cockcroft-Gault formula);
27. Adequate coagulation function: Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN, and international normalizedratio (INR) ≤ 1.5 × ULN.
28. Adequate cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram within 28 days beforeenrollment; New York Heart Association (NYHA) Class < grade 3.

Exclusion Criteria:

• Participants will be not enrolled if they meet any of the following exclusion criteria: Neoplasm-related criteria:

1. Has more than 2 primary malignancies (except curatively treated non-melanoma skincancer, in situ disease, and other curatively malignancies have considered cured)within 5 years before signing of Informed Consent Form.
2. Has received chemotherapy within 3 weeks, or have received anti-tumor treatmentincluding radiation therapy, biologic therapy, endocrine therapy, immunotherapy, etc.within 4 weeks before the first dose of investigational product; or participants withthe following conditions: Medication of nitrosourea or mitomycin C within 6 weeks before the first dose ofinvestigational drug; Medication of oral fluoropyrimidines and small molecule targetedagents within 5 half-lives before the first dose of investigational drug; Medicationof traditional Chinese medicine with anti-tumor indication within 2 weeks before thefirst dose of investigational drug.
3. Medication of other unmarketed investigational drugs or therapies within 4 weeksbefore the first dose of investigational drug.
4. Presence of brain metastases and/or leptomeningeal carcinomatosis. Participantspreviously treated for brain metastases may be considered to be enrolled in thisstudy, provided they have been in stable condition for at least 1 month, have noprogression confirmed by radiographic examination within 4 weeks before the first doseof study treatment, all neurological symptoms have stabled, there is no evidence ofnew or enlarging brain metastases, and radiation or surgical therapy is discontinuedfor at least 28 days before the first dose of study treatment and steroid therapy atthe dose of ≤10 mg/day or similar drugs at equivalent dose within 14 days before thefirst dose and during the study. This exception does not include carcinomatousmeningitis, which should be excluded regardless of clinical stability.
5. Has previously received same target therapy.
6. Has adverse reactions from previous anti-tumor treatment that have not recovered to ≤CTCAE 5.0 Grade 1 (except for toxicities without safety risks as determined by theinvestigator, such as alopecia, hypothyroidism stably managed by hormone replacementtherapy, etc.). General conditions:
7. Has underwent major organ surgery (excluding biopsy) or significant trauma within 4weeks before the first dose of investigational drug or requiring elective surgeryduring the study.
8. Has vaccinated with attenuated live vaccines (except for SARS-CoV-2 vaccination)within 4 weeks before the first dose of investigational drug.
9. Has mucosal or internal bleeding for non-traumatic reason within 4 weeks before thefirst dose of investigational drug.
10. Has received treatment with systemic corticosteroids (prednisone at >10 mg/day, orsimilar drugs at equivalent dose) or other immunosuppressive agents within 14 daysbefore the first dose of investigational drug, with the following exceptions: Treatment with topical, ocular, intra-articular, intranasal, and inhaledcorticosteroids; Short-term use of glucocorticoids for prophylaxis (e.g., preventionof contrast media allergy).
11. Has pulmonary disease that severely impact pulmonary function, including, but notlimited to, potential pulmonary disease, any autoimmune diseases, connective tissuediseases, or inflammatory diseases involving the pulmonary, or pneumonectomy.
12. Has history of non-infectious interstitial lung disease (ILD)/pneumonitis thatrequired steroids, or current ILD/pneumonia, or suspected ILD/pneumonia that cannot beexcluded by imaging examination at screening.
13. Has active pulmonary tuberculosis.
14. Has active infection requiring systemic therapy.
15. Has positive results in virus serology tests (participants receiving antiviralprophylaxis other than interferon are allowed to be enrolled): Positive result of HIV antibody; Or, positive for both HBsAg and HBV-DNA (i.e., HBVDNA ≥LLOD); Or, positive for HCV Ab (except HCV-RNA < LLOD).
16. Has positive result for covid-19 nucleic acid test.
17. Medical history of serious cardiovascular and cerebrovascular diseases, including butnot limited to: Severe arrhythmia or conduction abnormalities, such as ventricular arrhythmiarequiring clinical intervention, or atrioventricular block Ⅱ~Ⅲ degree;Fridericia-corrected QT interval (QTcF) prolongation to >450 milisecond (ms) for malesand > 470 ms for females; Acute coronary syndrome, aortic dissection, stroke ortransient ischemic attack (TIA) within 6 months before the first dose; New myocardialinfarction or unstable angina within 6 months before the first dost; Clinicallyuncontrolled hypertension;
18. Has clinically uncontrolled effusion in third spacing, deemed as inappropriate forenrollment by the investigator.
19. Hypersensitivity or delayed hypersensitivity to certain components or analogues of theinvestigational drug.
20. Has drug abuse or any other medical conditions, such as clinically significantpsychological conditions that may interfere with study participation or the results ofthe clinical study as per investigator discretion.
21. Has alcohol or drug dependence.
22. Females who are pregnant or breastfeeding, or males/females who plan to father achild/get pregnant.
23. Poor compliance as per investigator discretion, has history of other serious systemicdiseases, or unsuitable to participate this clinical study for some reasons.