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

Phase 1

Active, not recruiting

• Conditions: Melanoma Excluding Uveal Melanoma; Ovarian Cancer, Epithelial; Head and Neck Squamous Cell Carcinoma; Non-small Cell Lung Cancer, Squamous or Non-squamous; Renal Cell Carcinoma, Clear Cell; TNBC - Triple-Negative Breast Cancer; Colorectal Cancer; Castration-resistant Prostate Cancer; Urothelial Carcinoma
• Interventions: Biological: XmAb®808; Biological: Keytruda® (pembrolizumab)

• Registration Number: NCT05585034
• Lead Sponsor: Xencor, Inc.

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).

Study Timeline

• Study First Submitted: 2022-10-11
• Study First Submitted QC: 2022-10-13
• Study First Posted: 2022-10-18
• Study Start: 2022-12-14
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-24
• Last Update Posted: 2025-03-28
• Primary Completion: 2025-06
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Escalation and Expansion XmAb®808 administered in combination with pembrolizumab	XmAb®808	XmAb®808 in combination with pembrolizumab
Dose Escalation and Expansion XmAb®808 administered in combination with pembrolizumab	Keytruda® (pembrolizumab)	XmAb®808 in combination with pembrolizumab

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Measurement of Cmax	Through study completion, Up to 5 years	Peak plasma concentration (Cmax)
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
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
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
Measurement of AUCtau	Through study completion, Up to 5 years	Area under the plasma concentration versus time curve (AUCtau)

Trial Locations

Locations (12)

UCLA Hematology/Oncology; 🇺🇸 Los Angeles, California, United States

Sarah Cannon Research Institute at HealthONE; 🇺🇸 Denver, Colorado, United States

Florida Cancer Specialists; 🇺🇸 Sarasota, Florida, United States

Winship Cancer Institute, Emory University; 🇺🇸 Atlanta, Georgia, United States

Northwestern Memorial Hospital; 🇺🇸 Chicago, Illinois, United States

Columbia University Irvine Medical Center; 🇺🇸 New York, New York, United States

University of Cincinnati Medical Center; 🇺🇸 Cincinnati, Ohio, United States

UPMC Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Huntsman Cancer Institute, University of Utah; 🇺🇸 Salt Lake City, Utah, United States

Froedtert Hospital & The Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States