An Open-label, Randomized Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of the Combination Therapy of SLC-3010 and Axitinib Compared to Axitinib Monotherapy as a Second-line Treatment for Locally Advanced or Metastatic Clear Cell Renal Cell Carcinoma
This study is a phase 2, randomized study to evaluate the efficacy and safety of SLC-3010 in combination with axitinib versus axitinib monotherapy as second-line treatment in patients with locally advanced or metastatic clear cell renal cell carcinoma (ccRCC). This study includes a screening period, a treatment period, and a follow-up period. All patients will complete a screening period of up to 28 days. During the treatment period, patients will receive either SLC-3010 in combination with axitinib or axitinib monotherapy. Treatment may continue until the occurrence of unacceptable toxicity related to the study intervention, patient refusal for further participation, or disease progression. The patients will be followed up for disease progression and survival for up to 2 years after discontinuation of the study intervention, or until death, consent withdrawal, or the end of this clinical trial, whichever occurs first. For patients who withdraw consent, survival will be followed up via telephone or site visits every 2 months up to death or 12 months after the first administration of the last patient, whichever occurs first, depending on their consent for follow-up. This study consists of two parts: Part 1 is the safety run-in phase for SLC-3010 in combination with axitinib, and Part 2 is a randomized phase 2 trial to compare SLC-3010 in combination with axitinib and axitinib monotherapy.
• Histologically or cytologically confirmed diagnosis of locally advanced or metastatic ccRCC.
∙ Part 1 (Safety Run-in): At least one first-line treatment of standard of care in the recurrent/metastatic setting.
‣ Part 2 (Phase 2): Anti-PD-1 (Programmed Cell Death Protein 1) or anti-PD-L1 (Programmed Cell Death-Ligand 1) monotherapy or combination therapy as first-line treatment in the recurrent/metastatic setting.
• At least one measurable lesion as defined by RECIST (Response Evaluation Criteria in Solid Tumors) v1.1.
• Male or female patients aged ≥ 19 years at the date on which the informed consent is signed.
• Ability and willingness to provide written informed consent and to comply with all study procedures.
• Estimated life expectancy of ≥ 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Adequate organ functions as defined below. System organ class Laboratory test results
• \- Hematology
• : Absolute neutrophil count (ANC) ≥ 1500 cells/μL without the support of granulocyte colony-stimulating factor (G-CSF) within 2 weeks prior to the first dose of the study intervention.
• Platelet count ≥ 100,000/μL without the support of transfusion within 2 weeks prior to screening laboratory sample collection.
• Hemoglobin ≥ 9 g/dL without the support of transfusion within 2 weeks prior to screening laboratory sample collection.
⁃ Coagulation
‣ :International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × the upper limit of normal (ULN). If the patient is receiving anticoagulant therapy, PT shall be within the therapeutic range for the intended use of anticoagulants.
⁃ Kidney
‣ :Estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. ≥ 40 mL/min/1.73 m2
⁃ Liver :Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for patients with Gilbert's syndrome), or if total bilirubin is \> 1.5 × ULN, direct bilirubin ≤ ULN.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN for patients with documented liver metastases).
• Albumin ≥ 2.8 g/dL
• If there were any clinically significant toxicities from prior therapies, they shall have resolved to Grade 0 or Grade 1 according to the NCI CTCAE v5.0 (Alopecia and ≤ Grade 2 endocrine-related adverse events related to prior immunotherapy (e.g., immune checkpoint inhibitors) that require medical treatment or hormone replacement therapy are considered acceptable for study participation.).
• Male and female patients of childbearing potential shall agree to use existing, highly effective contraception methods with the failure rate of \<1% (Appendix 1) during the treatment period and for 3 months after the last administration of the study intervention. Acceptable methods shall include barrier methods such as spermicide condoms or diaphragms. Women of childbearing potential (WOCBP) are defined as females who have experienced menarche and are not postmenopausal (including amenorrhea for at least 2 years without hormone therapy or surgical sterilization).
⁃ WOCBP shall have a documented negative serum or urine pregnancy test at screening, performed within 3 days prior to the first administration of the study intervention. For non-childbearing females, one of the following shall be documented:
• Postmenopausal status, defined as the absence of regular menstruation for at least 12 consecutive months with a documented serum follicle-stimulating hormone (FSH) level within the laboratory reference range for postmenopausal women, or
∙ Documented history of hysterectomy or bilateral oophorectomy, or
∙ Medically confirmed ovarian failure.