Clinical trial NCT06428331: A Study of SKB518 in Patients With Advanced Solid Tumors
Official title: A Phase 1, Multicenter, Open-label First-In-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of SKB518 in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-05-24
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a first-in-human (FIH), phase 1, multicenter, open-label, dose-escalation study of SKB518 to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity in adult subjects with advanced or metastatic solid tumor relapsed/refractory to standard therapies or for which no effective standard therapy is available.

Detailed description: This is a first-in-human (FIH), phase 1, multicenter, open-label, dose-escalation study of SKB518 to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity in adult subjects with advanced or metastatic solid tumor relapsed/refractory to standard therapies or for which no effective standard therapy is available. Dose escalation and de-escalation decisions are based on the mTPI-2 design and depend on the number of subjects enrolled and the number of DLTs observed at the current dose level.

Eligibility criteria: Inclusion Criteria:

1. Subject must be at least 18 years of age at the time of signing the informed consent;
2. Histological or cytological diagnosis of solid tumor that is advanced/metastatic solid tumor by pathology report and have progressed on, have been intolerant to, or have been ineligible for standard of care treatments.
3. Subjects able to provide tumor blocks or 8\~10 slides \[fresh paraffin-embedded tumor tissue or archived paraffin-embedded tumor tissue (maximum time limit is not more than 2 years)\] before the first dose of study intervention for biomarkers testing.
4. At least one measurable lesion can be accurately measured per RECIST v1.1 as determined by the local site investigator/radiology assessment. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
5. Subjects with Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
6. Life expectancy of at least 3 months as assessed by the investigators.
7. Subjects with adequate organ and bone marrow function confirmed by laboratory results within 7 days prior to the first dose.
8. Has recovered from all toxicities from previous therapy with the exception of stable, chronic (\>3 months) toxicities not considered a safety risk (e.g. alopecia, vitiligo), after consultation with the Sponsor.
9. Subjects of childbearing potential (male or female) must use effective medical contraception during the study until 6 months after the last dose.
10. Subjects must be able to provide documented voluntary informed consent.

Exclusion Criteria:

1. Has known active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis are not eligible.
2. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years.
3. Has a history of major cardiovascular, cerebrovascular or thromboembolic diseases.
4. Has serious and/or uncontrolled concomitant diseases.
5. Has known active tuberculosis.
6. Has known human immunodeficiency virus (HIV) infection that is not well controlled.
7. Has any active viral hepatitis, hepatitis B or hepatitis C.
8. Has had major surgery within 28 days prior to the first dose.
9. Has known allergy or hypersensitivity to SKB518, or the excipients of SKB518.
10. Has a history of interstitial lung disease (ILD) or a history of non-infectious pneumonitis that required steroids.
11. Clinically serious lung injuries caused by lung diseases.
12. History of documented severe dry eye syndrome.
13. Has a history of allogeneic tissue/solid organ transplant.
14. Has known uncontrollable effusion.
15. Subjects who are vaccinated with live vaccine within 30 days before the first dose, or plan to be vaccinated with live vaccine during the study period.
16. Has received strong cytochrome P450 (CYP3A4) inhibitors or inducers, or has received BCRP inhibitors within 2 weeks prior to the first dose.
17. Subjects who received any chemotherapy, radiotherapy, immunotherapy, or biologic therapy treatment within 4 weeks; or who received any small molecular tyrosine kinase inhibitor, antitumor hormonal therapy, system immune-stimulator, or therapy with traditional Chinese medicines approved for antitumor treatment, etc. within 2 weeks before the first dose.
18. Has an active infection requiring systemic therapy.
19. Subjects with the disease that requires systemic corticosteroid therapy (prednisolone or equivalent dose of similar drugs at a dose of \>10 mg/d) or other immunosuppressive therapy within 14 days before the first dose.
20. Is currently participating and receiving study therapy in a study of an investigational agent or has participated and received study therapy in a study of an investigational agent or has used an investigational device within 28 days of fist dose.
21. Before the first dose, the subject's condition deteriorates rapidly.
22. Has a known psychiatric or substance abuse disorders.
23. The Investigator considers other situations that will interfere with the evaluation of the study intervention or the safety of the subjects or the interpretation of the results of the study.

Primary outcomes:
measure: Number of subjects achieving Dose-limiting toxicity (DLT)
timeFrame: From data of initial dose until up to 21 days for treatment
measure: Maximum Tolerated Dose (MTD)
timeFrame: From data of initial dose until up to 21 days for treatment
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 24 months
measure: Progression Free Survival (PFS)
timeFrame: Up to 24 months
measure: Duration of Response (DOR)
timeFrame: Up to 24 months
measure: Overall Survival (OS)
timeFrame: Up to 24 months
Other outcomes:
Locations:
Study officials:
affiliation: Fudan University
name: Jian Zhang
role: STUDY_CHAIR
affiliation: Fudan University
name: Xiaohua Wu
role: STUDY_CHAIR
References: