A Study of SKB315 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a multicenter, open-label, multiple-dose dose finding and expansion study to evaluate the safety, tolerability, pharmacokinetic(PK) profile, and anti-tumor efficacy of SKB315 for injection in patients with advanced solid tumors.

Detailed Description
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This is a multicenter, open-label, multiple-dose dose finding and expansion study to evaluate the safety, tolerability, PK profile, and anti-tumor efficacy of SKB315 for injection in patients with advanced solid tumors.The study is divided into Phase 1a and Phase 1b: Phase 1a is a dose escalation study to determine the maximum tolerated dose(MTD); Phase 1b is a dose expansion study to conduct preliminary evaluation of anti-tumor efficacy and further evaluation of safety, tolerability, PK, and immunogenicity of SKB315.

Official Title
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A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of SKB315 for Injection in Patients With Advanced Solid Tumors Expressing Claudin18.2

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: SKB315 for injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged 18 to 80 years (inclusive) at the time of signing the informed consent form (ICF); Patients with histologically and/or cytologically confirmed advanced solid tumors who have failed standard of care, or who have no available standard of care regimen, or who are unqualified for standard of care; Consent to provide archival or fresh tumor tissue slides for immunohistochemistry (IHC) assessment, and advanced solid tumors with Claudin 18.2 expression as determined by IHC; Presence of at least one measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; Eastern Cooperative Oncology Group (ECOG) score of 0 or 1; Estimated survival ≥ 3 months as judged by the investigator; Adequate organ and bone marrow function (no blood components and cytokines are allowed within 2 weeks prior to the first dose) ; Have recovered to ≤ Grade 1 (according to national cancer institute (NCI) common terminology criteria adverse events (CTCAE) V5.0) from previously treated toxicity prior to the first dose of study treatment; Patients of childbearing potential (male or female) must use effective medical contraception during the study and for 6 months after the end of dosing; Patients voluntarily participate in the study, sign the ICF, and will be able to comply with the protocol-specified visits and relevant procedures. Exclusion Criteria: Received other drugs in clinical study, major surgeries, or any other anti-tumor therapies within 4 weeks prior to the first dose of study treatment; Received any previous therapy targeting Claudin18.2; Plan to receive any other anti-tumor therapy during the study; Received strong cytochrome P450 3A4(CYP3A4) inhibitors or inducers within 2 weeks prior to the first dose of study treatment or within 5 half-lives of drug elimination, whichever is longer; Have other malignancies within 5 years prior to signing of ICF; Pregnant or lactating women; Known history of allergy to any component of SKB315 or other monoclonal antibodies (mAbs); Known history of alcohol abuse (consumption of more than 14 units of alcohol per week or drug abuse); Patients with active hepatitis B or hepatitis C; Human immunodeficiency virus (HIV) positive; Active severe digestive disease; History of major cardiovascular diseases Confirmed serious lung disease or lung disease that may impair the respiratory reserve function of the patient as judged by the investigator; History of serious dementia, altered mental status, or any psychiatric disorder; Concomitant or known metastases to brain or central nervous system; Have clinically significant systemic diseases that may adversely affect the safety of the study; Subjects who may have poor compliance with the clinical study or have other factors based on which the investigator considers that the subjects are not appropriate to participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1a：Dose escalation<br>Eleven dose levels are tentatively planned for Phase 1a | Drug: SKB315 for injection<br>* SKB315 for injection is an Antibody Drug Conjugates (ADC) drug targeting Claudin18.2. The strength of SKB315 is 200 mg/vial.<br>|
| Experimental: Phase 1b: Dose expansion<br>The dose of SKB315 for injection in Phase 1b is selected based on the Phase 1a monotherapy dose escalation study. | Drug: SKB315 for injection<br>* SKB315 for injection is an Antibody Drug Conjugates (ADC) drug targeting Claudin18.2. The strength of SKB315 is 200 mg/vial.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1a: Dose Limiting Toxicities (DLT) | Incidence of Dose Limiting Toxicities | From data of initial dose until up to 21/28 days for treatment | 
| Phase 1b: Objective Response Rate (ORR) | The sum of the number of cases with Complete Response (CR) and Partial Response (PR) in all treated tumor patients (CR + PR) divided by the total number of cases. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS: Time from start of treatment to progression of disease (PD) or death, whichever occurs first, in patients with tumors. | Up to 2 years | 
| Duration of Response (DOR) | DOR: Time from the start of the first assessment of CR or PR in tumor patients to PD or death due to any reason. | Up to 2 years | 
| Overall Survival (OS) | OS: Time from start of treatment to death due to any reason. | Up to 2 years |