Study of SKB264 in patients with advanced and hard-to-treat cancers who have not responded well to standard treatments.

Phase 1

Conditions: Metastatic or locally advanced unresectable solid tumors progressing after available standard therapies
MedDRA version: 21.1Level: PTClassification code: 10028997Term: Neoplasm malignant Class: 100000004864
Therapeutic area: Diseases [C] - Neoplasms [C04]

Registration Number: CTIS2023-508700-38-00

Lead Sponsor: Sichuan Kelun-Biotech Biopharmaceutical Co. Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1261

Inclusion Criteria

Patients must be able to provide documented voluntary informed consent., Creatinine clearance = 30 mL/min calculated by Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), or Modification of Diet in Renal Disease (MDRD) formulas. Note that 4-hour urine collection is not required but is allowed., For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception during study treatment., Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia and vitiligo. Note: Subjects with endocrine AE of any grade are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic., Expected survival = 3 months., ECOG Performance Status 0 or 1., Male or female patient aged = 18 years., Histologically or cytologically documented, incurable, locally advanced, recurrent or metastatic cancer., Measurable disease by CT/MRI., Patients should have an unresectable locally advanced or metastatic solid tumor that is refractory to standard therapies., Neutrophil count = 1.5×109/L, platelet count = 100×109/L, and hemoglobin = 9 g/dL (without receiving blood transfusion, erythropoietin, recombinant human thrombopoietin or colony stimulating factor treatment within 2 weeks before screening)., International normalized ratio (INR) and activated partial thromboplastin time (aPTT) = 1.5×ULN., Serum total bilirubin = 1.5 ×ULN (Patients with known Gilbert disease who have serum total bilirubin level = 3 ×ULN may be enrolled), aspartate aminotransferase (AST), alanine aminotransferase (ALT)= 2.5 × upper limit of normal (ULN), with the exception of patients with hepatic metastases (ALT and AST = 5 × ULN).

Exclusion Criteria

Any patient who was treated in the Phase I part of this study., Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure (New York Heart Association) III or IV, unstable angina pectoris that couldn’t be controlled by medication, history of myocardial infarction during the last 6 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia)., Subjects with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, or other active CNS metastases. For further details refer to protocol., Patients with active second primary cancers (except for cured in situ nonmelanoma skin cancer and in situ cervical cancer with no relapse in the last 3 years, or other malignant cancers that have been cured and no evidence of recurrence)., Require supplemental oxygen for daily activities., Documented Grade = 2 peripheral neuropathy., History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, corneal disease that prevents/delays corneal healing, macular degeneration., Patients previously treated with TROP2 targeted therapies at any time for early stage or metastatic disease., Left ventricular ejection fraction < 45% determined by echocardiogram or multiple-gated acquisition scan., Resting QTcF > 480 msec at baseline., Ascites requiring paracentesis >1 per week., Any standard cancer therapy (e.g. chemotherapy, hormonal therapy, immunotherapy, biologic therapy treatment, etc.) within 4 weeks, or any small molecular tyrosine kinase inhibitor (TKI), radiotherapy or therapy with traditional Chinese medicines approved for anti-tumor treatment within 2 weeks before first infusion of study drug., Symptomatic pleural effusion (< 90% oxygen saturation)., History of interstitial lung diseases (ILD) or non-infectious pneumonitis requiring steroid treatments, or current ILD/pneumonitis, or where ILD/pneumonitis cannot be ruled out by imaging at screening; severe pulmonary dysfunction caused by lung diseases., New diagnosed thromboembolic events that requires therapeutic intervention over the last 6 months (patients with stable control of lower limb deep venous thrombosis are allowed)., Known allergic to any components of SKB264, including excipients (including polysorbate-20); or history of severe hypersensitivity to another biologic therapy., The investigator considers other situations that patients are not appropriate to participate in this trial.For participants in the EU, this includes those who, in the opinion of the investigator, could benefit from existing alternative treatment options within the current ESMO ( European Society For Medical Oncology) guidelines for each indication and setting. For further details please refer to protocol., Any major surgical procedure within 4 weeks of first infusion of study drug., Diagnosed disease as below or active infection including: Hepatitis B/C or cirrhosis. With serious infections within 4 weeks prior to the first dose of study intervention (including but not limited to comorbidity, sepsis or severe pneumonia that require hospitalization) or concomitant infections requiring systemic antibiotic treatment within 2 weeks prior to the first dose of study intervention., Have known prior positive test results or medical history for human immunodeficiency virus., Uncontrolled hypertension (systolic blood pressure = 160 mmHg and/or diastolic blood pressure =100

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the objective response rate (ORR) [Complete Response (CR) + Partial Response (PR)] of SKB264 when administered intravenously (IV) as monotherapy at the RDEs to patients with metastatic or locally advanced unresectable tumors.;Secondary Objective: To obtain additional characterization of the safety of SKB264 at the RDEs., To evaluate efficacy in patients treated with SKB264 as monotherapy based on: - DOR - PFS - OS, To assess the immunogenicity of SKB264., To characterize the PK of SKB264- ADC, SKB264-TAB, and free KL610023 payload., To assess levels of TROP2 expression in tumor tissue and correlation of those levels with responses;Primary end point(s): ORR (the percentage of patients who achieve CR/PR) per RECIST 1.1

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Percentage of patients with adverse events, serious adverse events DOR.PFS (time frame: baseline to the end of the study).OS (time frame: baseline to the end of the study).Immunogenicity of SKB264.PK parameters for SKB264-ADC, SKB264-TAB, and free KL610023 payload.Levels of TROP2 expression in tumor tissue and correlation of those levels with responses.