Study of XmAb®819 in Subjects With Advanced Clear Cell Renal Cell Carcinoma
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety and tolerability of intravenous (IV) administration of XmAb®819 in subjects with relapsed or refractory clear cell renal cell carcinoma and to identify the minimum safe and active dose.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 including the priming dose(s), the minimum safe and biologically active dose, and the recommended dose (RD); 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose Escalation and Expansion Part A, Dose Escalation: Part A will enroll subjects with ccRCC to establish a priming dose, step-up priming dose(s), a cohort limit dose, and the dosing schedule. Includes weekly intravenous dosing. Part B, Dose Expansion: Part B will enroll in two stages to further evaluate safety and tolerability, as well as provide an initial evaluation of efficacy for the priming dose(s), the recommended dose of the cohort limit dose, and overall schedule established in Part A for subjects with ccRCC. Includes weekly intravenous dosing and multiple dose levels can be tested. |
Biological: XmAb819
Monoclonal Bispecific Antibody
|
Outcome Measures
Primary Outcome Measures
- Safety and Tolerability as assessed by incidence of TEAEs, laboratory tests, clinical findings [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
- Safety and Tolerability as assessed by incidence of 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.
Secondary Outcome Measures
- PK characterization [56 days]
Peak plasma concentration (Cmax)
- PK characterization [56 days]
Area under the plasma concentration versus time curve (AUCtau)
- Antitumor activity of XmAb819 [42 days]
Objective response rate (RECIST 1.1 assessement of CT/MRI imaging)
- Antitumor activity of XmAb819 [42 days]
Progression-free survival (RECIST 1.1 assessement of CT/MRI imaging)
- Antitumor activity of XmAb819 [42 days]
Duration of response (RECIST 1.1 assessement of CT/MRI imaging)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subjects must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by the local site investigator or radiology department
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Subjects who have relapsed and refractory ccRCC and had undergone disease progression on standard-of-care therapies
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ECOG performance status of 0 or 1
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All subjects in Part B, dose expansion, must have a tumor lesion that can be biopsied and must agree to a fresh biopsy during screening and second biopsy to be collected between Days 1 to 8 of Cycle 2
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All subjects in Part A, dose escalation, must have adequate tumor sample (slides or archival FFPE blocks). Expected are subjects who consent to having a fresh tumor biopsy to provide a fresh tumor sample instead of the archival tumor sample
Exclusion Criteria:
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Prior treatment with an investigational anti-ENPP3/CD203c therapy
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History of serious allergic or anaphylactic/hypersensitivity reaction to monoclonal antibody therapy
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Systemic antineoplastic therapy within 5 half-lives on the first dose of study treatment.
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Failure to recover from any clinically significant toxicity related to previous anticancer treatment
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Have known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable,
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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)
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Evidence of any serious infection requiring IV anti-infective treatment within 14 days prior to the first dose of study drug
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Have a known additional malignancy that is progressing or has required active treatment within the past 2 years
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Medical Oncology and Therapeutics Research, City of Hope | Duarte | California | United States | 91010 |
| 2 | Sarah Cannon Research Institute, LLC | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- Xencor, Inc.
Investigators
- Study Director: Zequn (Tony) Tang, MD PhD, Xencor, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- XmAb819-01