A Randomized Open-Label Phase 3 Study of XL092 + Nivolumab vs Sunitinib in Subjects with Advanced or Metastatic Non-Clear Cell Renal Cell Carcinoma
- Conditions
- Advanced or Metastatic Non-Clear Cell Renal Cell CarcinomaMedDRA version: 21.1Level: LLTClassification code: 10038407Term: Renal cell cancer Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2022-501703-27-00
- Lead Sponsor
- Exelixis Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 363
Histologically confirmed nccRCC that is unresectable, advanced or metastatic. Histologic subtypes including papillary, unclassified, and translocation-associated are allowed. Among the eligible histologic subtypes, sarcomatoid features are allowed., Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45 years-of-age in the absence of other biological or physiological causes. In addition, females < 55 years-of-age must have a serum follicle stimulating hormone (FSH) level > 40 mIU/mL to confirm menopause). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff., Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1; Eisenhauer et al 2009) as determined by the Investigator. Measurable disease must be outside the radiation field if radiation therapy was previously administered., Available archival tumor biopsy material. If archival tissue is unavailable, must provide fresh tumor tissue biopsy prior to randomization., Recovery to baseline or = Grade 1 per CTCAE v5 from AE(s) related to any prior treatments unless AE(s) are deemed clinically nonsignificant by the Investigator and/or stable on supportive therapy., Age 18 years or older on the day of consent., Karnofsky Performance Status (KPS) = 70%., Adequate organ and marrow function, based upon all of the following laboratory assessments within 14 days prior to randomization: a.Absolute neutrophil count (ANC) = 1500/µL (= 1.5 GI/L) without granulocyte colony stimulating factor (G-CSF) support within 2 weeks before screening laboratory sample collection. b.Platelets = 100,000/µL (= 100 GI/L) without transfusion within 2 weeks before screening laboratory sample collection. c.Hemoglobin = 9 g/dL (= 90 g/L) without transfusion within 1 week before screening laboratory sample collection and no clinical evidence of bleeding. d.International Normalized Ratio (INR) = 1.5 and activated partial thromboplastin time (aPTT) = 1.2 × upper limit of normal (ULN). e.Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) = 3 × ULN. f.f. Total bilirubin = 1.5 × ULN (with the exception that total bilirubin for subjects with Gilbert’s disease = 3 × ULN). g.g. Calculated creatinine clearance = 40 mL/min (= 0.67 mL/sec) using the Cockcroft-Gault equation. h.h. Urine protein-to-creatinine ratio (UPCR) = 1 mg/mg (= 113.2 mg/mmol), or 24-h urine protein = 1 g. i.i. Negative hepatitis B surface antigen (HBsAg) test. j.j. Negative hepatitis C virus (HCV) antibody test, or positive HCV antibody test followed by a negative HCV RNA test and no ongoing anti-HCV therapy. Note: The HCV RNA test will be performed only for subjects who have a positive HCV antibody test., Capable of understanding and complying with the protocol requirements and must have signed the informed consent document., Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception during the course of the study and for the following durations after the last dose of study treatment (whichever is later): •through 186 day
Chromophobe, renal medullary carcinoma, and pure collecting duct histologic subtypes of nccRCC., History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent., Pregnant or lactating females., Inability or unwillingness to swallow tablets or receive IV administration, or presence of GI condition that might affect the absorption of study drug (eg, PEG tube)., Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies., Any other active malignancy within 2 years prior to randomization, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy. Incidentally diagnosed prostate cancer is allowed if assessed as stage = T2N0M0 and Gleason score = 6., Administration of a live, attenuated vaccine within 30 days before randomization. Note: If feasible, approved non-live vaccines for SARS-CoV-2 should be administered at least 2 weeks before randomization., Prior systemic anticancer therapy for unresectable locally advanced or metastatic nccRCC including investigational agents. Note: One prior systemic adjuvant therapy, including ICI therapy and excluding sunitinib, is allowed for completely resected RCC and if recurrence occurred at least 6 months after the last dose of adjuvant therapy., Radiation therapy for bone metastases within 2 weeks, any other radiation therapy within 4 weeks prior to randomization. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible., Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy (including radiosurgery) or surgically removed and stable for at least 4 weeks before randomization. Note: Subjects with an incidental finding of an isolated brain lesion < 1 cm in diameter may be eligible after Sponsor approval if the lesion is radiographically stable for 4 weeks before randomization and does not require treatment per Investigator judgement. Note: Eligible subjects must be neurologically asymptomatic and either off corticosteroids, or on a stable or decreasing dose of = 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization. Imaging performed within 28 days prior to randomization must document radiographic stability of CNS lesions, and must be performed after completion of any CNS-directed therapy. A stable dose of anticonvulsants is allowed., Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat nccRCC within 2 weeks before randomization., Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) and platelet inhibitors (eg, clopidogrel). Subjects who are receiving oral anticoagulants at the time of screening must be transitioned to LMWH prior to randomization with the last dose of oral anticoagulants at least 3 days or 5 half-lives prior to randomization, whichever is longer. Subjects who require treatment with platelet inhibitors (eg, clopidogrel) are not eligible. Allowed anticoagulants are: - Low-dose aspirin for cardioprotection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH), - Therapeutic doses of LMWH in subjects without known brain metastases., The subject has uncontrolled, significant intercurrent or recent illness including, bu
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the efficacy of XL092 in combination with nivolumab versus sunitinib in subjects with unresectable, locally advanced or metastatic nccRCC;Secondary Objective: Safety: to assess safety and tolerability, To characterize PK, quality of life, biomarkers, and healthcare resource utilization;Primary end point(s): Duration of Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), by Blinded Independent Radiology Committee (BIRC), Objective response rate (ORR) as assessed by BIRC per RECIST 1.1
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Duration of Overall Survival (OS)