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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05585034
• Other study ID #: XmAb808-01
• Status: Recruiting
• Phase: Phase 1
• Start date: December 14, 2022
• Est. completion date: December 2027

Study information

• Verified date: April 2024
• Source: Xencor, Inc.
• Contact: Michael Chiarella
• Phone: (858) 945-2415
• Email: mchiarella[@]xencor.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: December 2027
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Ovarian Epithelial
• Castration-resistant Prostate Cancer
• Colorectal Cancer
• Head and Neck Squamous Cell Carcinoma
• Melanoma
• Ovarian Cancer, Epithelial
• Renal Cell Carcinoma, Clear Cell
• Squamous Cell Carcinoma of Head and Neck
• TNBC - Triple-Negative Breast Cancer
• Triple Negative Breast Neoplasms
• Urothelial Carcinoma

Intervention

Biological:
• XmAb®808
Monoclonal bispecific antibody
• Keytruda® (pembrolizumab)
Monoclonal antibody

Locations

Country	Name	City	State
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	UCLA Hematology/Oncology	Los Angeles	California
United States	Froedtert Hospital & The Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Tennessee Oncology	Nashville	Tennessee
United States	Columbia University Irvine Medical Center	New York	New York
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Huntsman Cancer Institute, University of Utah	Salt Lake City	Utah
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Xencor, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Measurement of Cmax	Peak plasma concentration (Cmax)	Through study completion, Up to 5 years
Secondary	Measurement of AUCtau	Area under the plasma concentration versus time curve (AUCtau)	Through study completion, Up to 5 years
Secondary	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
Secondary	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
Secondary	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