Phase 1, First-in-human, Dose-finding and Expansion Study to Evaluate XmAb®808 in Combination With Pembrolizumab in Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of intravenous (IV) administration of XmAb808 in combination with pembrolizumab in subjects with selected advanced solid tumors and to identify the minimum safe and biologically effective/recommended dose (RD) and schedule for XmAb808.

Detailed Description
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This is a Phase 1, open-label, first-in-human (FIH), multiple-dose, dose escalation study with cohort expansion at the RD, designed to evaluate the safety and tolerability of XmAb808 in combination with pembrolizumab. This study will be conducted in 2 parts: Part A (dose escalation) and Part B (cohort expansion).

Official Title
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A Phase 1, First-in-Human, Dose-Finding and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Activity of XmAb®808 in Combination With Pembrolizumab in Selected Advanced Solid Tumors

Conditions
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Head and Neck Squamous Cell Carcinoma, Melanoma Excluding Uveal Melanoma, Non-small Cell Lung Cancer, Squamous or Non-squamous, Urothelial Carcinoma, Renal Cell Carcinoma, Clear Cell, Castration-resistant Prostate Cancer, Ovarian Cancer, Epithelial, TNBC - Triple-Negative Breast Cancer, Colorectal Cancer

Intervention / Treatment
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* Biological: XmAb®808
* Biological: Keytruda® (pembrolizumab)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Part A: Histologically confirmed advanced/metastatic castration-resistant prostate adenocarcinoma, epithelial ovarian cancer, head and neck squamous cell carcinoma, non-small cell lung cancer, urothelial carcinoma, melanoma, renal cell carcinoma, triple-negative breast cancer, or colorectal cancer that has progressed on standard therapies Part B: Histologically confirmed advanced/metastatic castration-resistant prostate cancer that is PD1-naïve; head and neck squamous cell carcinoma that is PD1-naïve or has progressed on prior PD1 therapy; or melanoma that is PD1-naïve or has progressed on prior PD1 therapy Measurable disease by RECIST 1.1; subjects with prostate cancer who have evaluable disease according to PCWG3 criteria may enroll Life expectancy > 3 months Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Key Exclusion Criteria: Subjects currently receiving other anticancer therapies Any prior treatment with an investigational agent targeting CD28 History of a life-threatening adverse event related to prior immunotherapy Known active central nervous system involvement by malignant disease. Subjects with previously treated brain metastases may participate provided they are radiologically and clinically stable

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 XmAb®808 administered in combination with pembrolizumab<br>XmAb®808 in combination with pembrolizumab | Biological: XmAb®808<br>* Monoclonal bispecific antibody<br>Biological: Keytruda® (pembrolizumab)<br>* Monoclonal 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 (TEAEs) | Safety and tolerability as assessed by incidence of TEAEs, including clinically significant changes in safety laboratory tests and clinical findings | Up to 5 years | 
| 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 | 49 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of Cmax | Peak plasma concentration (Cmax) | Through study completion, Up to 5 years | 
| Measurement of AUCtau | Area under the plasma concentration versus time curve (AUCtau) | Through study completion, Up to 5 years | 
| Objective Response Rate | Objective response rate by RECIST 1.1 assessment of CT/MRI imaging, as modified by PCWG3 for participants with prostate cancer | Through study completion, Up to 5 years | 
| Progression-free Survival | Progression-free survival by RECIST 1.1 assessment of CT/MRI imaging, as modified by PCWG3 for participants with prostate cancer | Through study completion, Up to 5 years | 
| Duration of Response | Duration of Response by RECIST 1.1 assessment of CT/MRI imaging, as modified by PCWG3 for participants with prostate cancer | Through study completion, Up to 5 years |