A Study of XmAb®662 as Monotherapy or in Combination With Pembrolizumab in Advanced Solid Tumors

A Phase 1, First-in-Human, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Activity of XmAb®662 in Monotherapy or in Combination With Pembrolizumab in Advanced Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of intravenous administration of XmAb662 monotherapy or in combination with pembrolizumab in subjects with advanced solid tumors and to identify the recommended dose regimen that is safe and biologically effective for XmAb662.

Study Overview

• Status: Terminated
• Conditions: Solid Tumors
• Intervention / Treatment: Biological: XmAb662; Biological: Keytruda® (pembrolizumab)

Detailed Description

This is a first-in-human (FIH), Phase 1, open-label, multicenter dose escalation study with cohort expansion at one or more recommended dose(s) (RDs), designed to evaluate the safety and tolerability of XmAb662 monotherapy or in combination with pembrolizumab in subjects with selected solid tumors that have progressed after standard/approved therapies, or for which there are no effective available therapies. This study will be conducted in 2 parts: dose escalation (Part 1) and dose expansion (Part 2), and subdivided into arms for XmAb662 monotherapy and XmAb662+pembrolizumab combination.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Advanced, recurrent or metastatic solid malignancy that is not amenable to curative-intent treatment and which has progressed after standard therapy appropriate for the following tumor type: Head and neck squamous cell carcinoma, melanoma, non-small cell lung cancer, small cell lung cancer (SCLC), urothelial carcinoma, colorectal cancer, gastric cancer, esophageal cancer, cervical cancer, hepatocellular carcinoma, Merkel cell carcinoma, renal cell carcinoma, endometrial cancer, cutaneous squamous cell carcinoma, breast cancer, ovarian cancer (epithelial), castration-resistant prostate cancer (adenocarcinoma)

Measurable disease by RECIST 1.1; subjects with prostate cancer who have evaluable disease according to PCWG3 criteria may enroll

Life expectancy of at least 3 months

Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

For dose escalation cohorts, subjects must have adequate archival tumor sample or willing to provide a fresh tumor

Adequate organ function

Exclusion Criteria:

Receiving treatment with the following therapies: Interleukin (IL)-12 either alone or as part of a treatment regimen; checkpoint inhibitors given within 4 weeks of study drug; other anticancer therapies, including chemotherapy or radiation therapy, given within 4 weeks of the start of study drug (palliative radiation given within a 1-week washout is allowed)

History of allergic or anaphylactic/hypersensitivity reaction to immunotherapy

History of a life-threatening (Grade 4) immune-related adverse event (irAE) related to prior immunotherapy or any prior irAE, regardless of grade

History or evidence of any clinically unstable/uncontrolled disorder, condition, or disease (including, but not limited to, cardiopulmonary, renal, metabolic, hematologic, or psychiatric) other than their primary malignancy

Known active central nervous system involvement by malignant disease; subjects with previously treated brain metastases may participate provided they are radiologically and clinically stable

For subjects receiving pembrolizumab, prior Grade 3 or Grade 4 infusion-related reactions to pembrolizumab, or known hypersensitivity to pembrolizumab

Other protocol defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation and Expansion XmAb662 administered as monotherapy	Biological: XmAb662; Intravenous (IV) administration
Experimental: Dose Escalation and Expansion XmAb662 administered in combination with pembrolizumab	Biological: XmAb662; Intravenous (IV) administration; Biological: Keytruda® (pembrolizumab); Intravenous (IV) administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 recommend dose(s)	First 3 weeks on treatment for each subject]
Incidence and severity 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 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of pharmacokinetics	Measurement of Cmax	56 Days
Characterization of pharmacokinetics	Measurement of AUC	56 Days
Objective response rate	Objective response rate by RECIST 1.1, as modified by PCWG3 for participants with prostate cancer	Up to 2 years
Progression-free survival	Progression-free survival by RECIST 1.1, as modified by PCWG3 for participants with prostate cancer	Up to 2 years
Duration of response	Duration of response by RECIST 1.1, as modified by PCWG3 for participants with prostate cancer	Up to 2 years

Collaborators and Investigators

• Sponsor: Xencor, Inc.
• Investigators: Study Director: Chet Bohac, MD, Executive Medical Director, Clinical Development

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2023
• Primary Completion (Actual): May 21, 2024
• Study Completion (Actual): May 21, 2024

Study Registration Dates

• First Submitted: June 23, 2023
• First Submitted That Met QC Criteria: August 10, 2023
• First Posted (Actual): August 18, 2023

Study Record Updates

• Last Update Posted (Actual): August 23, 2024
• Last Update Submitted That Met QC Criteria: August 21, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Advanced Solid Tumors; Metastatic Solid Tumors; pembrolizumab; interleukin-12; IL-12,
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: XmAb662-01

Drug and device information, study documents

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