Study of XmAb®819 in Subjects With Advanced Clear Cell Renal Cell Carcinoma

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1 Multiple Dose Study to Evaluate the Safety and Tolerability of XmAb819 in Subjects With Relapsed or Refractory Clear Cell Renal Cell Carcinoma

Conditions
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Clear Cell Renal Cell Carcinoma

Intervention / Treatment
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* Biological: XmAb819


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation and Expansion<br>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. | Biological: XmAb819<br>* Monoclonal Bispecific Antibody<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (safety and tolerability of XmAb819) | 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 | 28 days | 
| Incidence of dose limiting toxicities (DLTs) | Safety and tolerability as assessed by incidence of DLTs and all available data which will be used to determine the optimal dose regimen. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of Cmax | Peak plasma concentration (Cmax) | 56 days | 
| Measurement of AUCtau | Area under the plasma concentration versus time curve (AUCtau) | 56 days | 
| Objective Response rate | Objective response rate (RECIST 1.1 assessment of CT/MRI imaging) | 42 days | 
| Progression-free survival | Progression-free survival (RECIST 1.1 assessment of CT/MRI imaging) | 42 days | 
| Duration of response | Duration of response (RECIST 1.1 assessment of CT/MRI imaging) | 42 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ccRCC, RCC, Renal Cell Cancer, Kidney Cancer