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

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

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ben Thompson, MD PhD; Phone Number: (619) 517-7381; Email: bthompson@xencor.com
• Study Contact Backup: Name: Amber Sarot; Phone Number: (858) 245-9419; Email: asarot@xencor.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA Hematology/Oncology
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Sarah Cannon Research Institute at HealthONE
  • Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Winship Cancer Institute, Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern Memorial Hospital
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irvine Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • University of Cincinnati Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • UPMC Hillman Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • Huntsman Cancer Institute, University of Utah
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert Hospital & the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation and Expansion XmAb®808 administered in combination with pembrolizumab; XmAb®808 in combination with pembrolizumab	Biological: XmAb®808; Monoclonal bispecific antibody; Biological: Keytruda® (pembrolizumab); Monoclonal antibody

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Xencor, Inc.
• Investigators: Study Director: Ben Thompson, MD PhD, Xencor, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: October 11, 2022
• First Submitted That Met QC Criteria: October 13, 2022
• First Posted (Actual): October 18, 2022

Study Record Updates

• Last Update Posted (Estimated): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 9, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Breast Diseases; Head and Neck Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Ovarian Neoplasms; Carcinoma, Squamous Cell; Breast Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Carcinoma; Melanoma; Carcinoma, Ovarian Epithelial; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: XmAb808-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No