Study of XmAb®819 in Subjects With Advanced Clear Cell Renal Cell Carcinoma
- Conditions
- Clear Cell Renal Cell Carcinoma
- Interventions
- Biological: XmAb819
- Registration Number
- NCT05433142
- Lead Sponsor
- Xencor, Inc.
- Brief Summary
The purpose of this study is to assess the safety and tolerability of XmAb®819 administered intravenous (IV) or subcutaneous (SC) in subjects with relapsed or refractory clear cell renal cell carcinoma and to identify the minimum safe and biologically active dose and the recommended dose (RD).
- Detailed Description
This is a Phase 1, multicenter, open-label, multiple-dose study designed in 2 parts: Part A, dose escalation, and Part B, dose expansion. The study is designed to establish the dosing schedule of XmAb819 administered IV and the dosing schedule of XmAb819 administered SC. The study is designed to evaluate safety and tolerability; to assess PK/PD and immunogenicity; and to preliminarily assess antitumor activity of XmAb819 in subjects with ccRCC. All eligible subjects will have relapsed or refractory disease after standard therapy.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 95
- Subjects must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by the local site investigator. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Subjects who have relapsed and refractory ccRCC with evidence of disease progression on standard-of-care therapies
- ECOG performance status of 0 or 1.
- All subjects must have adequate tumor sample available (slides or archival FFPE blocks)
- Prior treatment with an investigational anti-ENPP3/CD203c therapy
- History of serious allergic or anaphylactic/hypersensitivity reaction to monoclonal antibody therapy
- Systemic antineoplastic therapy within 5 half-lives on the first dose of study treatment.
- Failure to recover from any clinically significant toxicity related to previous anticancer treatment
- Have known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable,
- Active known autoimmune disease (except that subjects are permitted to enroll if they have vitiligo; type 1 diabetes mellitus; residual hypothyroidism due to an autoimmune condition that is treatable with hormone replacement therapy only; psoriasis, atopic dermatitis, or another autoimmune skin condition that is managed without systemic therapy; or arthritis that is managed without systemic therapy beyond oral acetaminophen and nonsteroidal anti-inflammatory drugs)
- Evidence of any serious infection requiring IV anti-infective treatment within 14 days prior to the first dose of study drug
- Have a known additional malignancy that is progressing or has required active treatment within the past 2 years
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation and Expansion XmAb819 Dose Escalation (Part A): Part A will establish the dosing schedule for XmAb819 administered IV and the dosing schedule of XmAb819 administered SC in subjects with ccRCC. The dosing schedule includes the priming dose, step-up priming dose(s), the minimum safe and biologically active dose. Dose Expansion (Part B): Part B-1 may administer XmAb819 IV, and Part B-2 may administer XmAb819 SC.
- Primary Outcome Measures
Name Time Method Incidence of dose limiting toxicities (DLTs) 28 days Safety and tolerability as assessed by incidence of DLTs and all available data which will be used to determine the optimal dose regimen.
Incidence of treatment-emergent adverse events (safety and tolerability of XmAb819) 28 days Safety and tolerability as assessed by incidence of TEAEs; incidence of clinically significant changes in safety laboratory tests, PE findings, vital signs, and ECGs; incidence and severity of CRS
- Secondary Outcome Measures
Name Time Method Measurement of AUCtau 56 days Area under the plasma concentration versus time curve (AUCtau)
Objective Response rate 42 days Objective response rate (RECIST 1.1 assessment of CT/MRI imaging)
Progression-free survival 42 days Progression-free survival (RECIST 1.1 assessment of CT/MRI imaging)
Measurement of Cmax 56 days Peak plasma concentration (Cmax)
Duration of response 42 days Duration of response (RECIST 1.1 assessment of CT/MRI imaging)
Trial Locations
- Locations (8)
Memorial Sloan Kettering
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Department of Medical Oncology and Therapeutics Research, City of Hope
🇺🇸Duarte, California, United States
Sarah Cannon Research Institute, LLC
🇺🇸Nashville, Tennessee, United States
Duke University
🇺🇸Durham, North Carolina, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States