Clinical trial NCT05367635: A Study of SKB315 in Patients With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-05-10
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female patients aged 18 to 80 years (inclusive) at the time of signing the informed consent form (ICF);
2. 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;
3. 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;
4. Presence of at least one measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1;
5. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1;
6. Estimated survival ≥ 3 months as judged by the investigator;
7. Adequate organ and bone marrow function (no blood components and cytokines are allowed within 2 weeks prior to the first dose) ;
8. 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;
9. Patients of childbearing potential (male or female) must use effective medical contraception during the study and for 6 months after the end of dosing;
10. 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:

1. 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;
2. Received any previous therapy targeting Claudin18.2;
3. Plan to receive any other anti-tumor therapy during the study;
4. 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;
5. Have other malignancies within 5 years prior to signing of ICF;
6. Pregnant or lactating women;
7. Known history of allergy to any component of SKB315 or other monoclonal antibodies (mAbs);
8. Known history of alcohol abuse (consumption of more than 14 units of alcohol per week or drug abuse);
9. Patients with active hepatitis B or hepatitis C;
10. Human immunodeficiency virus (HIV) positive;
11. Active severe digestive disease;
12. History of major cardiovascular diseases
13. Confirmed serious lung disease or lung disease that may impair the respiratory reserve function of the patient as judged by the investigator;
14. History of serious dementia, altered mental status, or any psychiatric disorder;
15. Concomitant or known metastases to brain or central nervous system;
16. Have clinically significant systemic diseases that may adversely affect the safety of the study;
17. 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.

Primary outcomes:
measure: Phase 1a: Dose Limiting Toxicities (DLT)
timeFrame: From data of initial dose until up to 21/28 days for treatment
measure: Phase 1b: Objective Response Rate (ORR)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to 2 years
measure: Duration of Response (DOR)
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University Cancer Institute and Hospital
name: Yi Ba, Professor
role: PRINCIPAL_INVESTIGATOR
References: