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
Conditions
Brief summary
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
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).
Interventions
BIOLOGICALXmAb®808
Monoclonal bispecific antibody
BIOLOGICALKeytruda® (pembrolizumab)
Monoclonal antibody
Sponsors
Xencor, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events (TEAEs) | Up to 5 years | Safety and tolerability as assessed by incidence of TEAEs, including clinically significant changes in safety laboratory tests and clinical findings |
| Incidence of dose-limiting toxicities (DLTs) | 49 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
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Through study completion, Up to 5 years | Objective response rate by RECIST 1.1 assessment of CT/MRI imaging, as modified by PCWG3 for participants with prostate cancer |
| Measurement of Cmax | Through study completion, Up to 5 years | Peak plasma concentration (Cmax) |
| Duration of Response | Through study completion, Up to 5 years | Duration of Response by RECIST 1.1 assessment of CT/MRI imaging, as modified by PCWG3 for participants with prostate cancer |
| Progression-free Survival | Through study completion, Up to 5 years | Progression-free survival by RECIST 1.1 assessment of CT/MRI imaging, as modified by PCWG3 for participants with prostate cancer |
| Measurement of AUCtau | Through study completion, Up to 5 years | Area under the plasma concentration versus time curve (AUCtau) |
Countries
United States
Outcome results
None listed