Safety and Efficacy of XmAb18087 ± Pembrolizumab in Advanced Merkel Cell Carcinoma or Extensive-stage Small Cell Lung Cancer

A Phase 1b/2 Multiple-Dose Study to Evaluate the Safety and Efficacy of XmAb18087 ± Pembrolizumab in Subjects With Advanced Merkel Cell Carcinoma or Extensive-stage Small Cell Lung Cancer (DUET-1-02) Protocol

This is a Phase 1b/2, multiple-dose study designed to describe safety and efficacy, and to assess PK and immunogenicity of XmAb18087 monotherapy and in combination with pembrolizumab in participants with metastatic Merkel cell (MCC) or locoregional MCC that has recurred after locoregional therapy with surgery and/or radiation therapy, and mAb18087 monotherapy in participants with extensive-stage small cell lung cancer (SCLC) that has progressed after standard therapies.

This study was terminated by the sponsor. No participants enrolled in Part B.

Study Overview

• Status: Terminated
• Conditions: Small Cell Lung Cancer; Merkel Cell Carcinoma
• Intervention / Treatment: Biological: XmAb18087; Drug: XmAb18087 ± Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • OU Health, Stephenson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington
    • Seattle, Washington, United States, 98109
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Able to provide written informed consent
• Adult participants ≥ 18 years
• Disease measurable by RECIST 1.1 criteria using either computed tomography (CT) or magnetic resonance imaging (MRI) scan
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• All participants must have adequate archival tumor sample (slides or archival formalin-fixed paraffin-embedded [FFPE] block[s] containing tumor that has not been previously irradiated
• Female participants of childbearing potential must agree to use a highly effective method of birth control during and for 4 weeks after completion of study. success), or sexual abstinence
• Fertile male participants must be willing to practice a highly effective method of birth control for the duration of the study and continuing for 4 weeks after the last dose of XmAb18087 or pembrolizumab (when applicable
• Able and willing to complete the entire study according to the study schedule

Additional Inclusion Criteria for Part A and Part B Cohorts:

• Histologically or cytologically confirmed metastatic MCC or locoregional MCC that has recurred following standard locoregional therapy with surgery and/or radiation therapy.

Additional Inclusion Criteria for Part A Cohorts:

• Participants must have progressed on or been ineligible for treatment with anti-PD1 or anti-PDL1 therapy.

Additional Inclusion Criteria for Part B Cohorts:

• Participants must be eligible to receive pembrolizumab as standard of care.

Additional Inclusion Criteria for Part C Cohorts:

• Histologically or cytologically confirmed extensive-stage SCLC that has progressed following standard therapies

Exclusion Criteria:

Additional Exclusion Criteria for Part B Cohorts: XmAb18087 in Combination with Pembrolizumab

• Prior treatment with therapeutics directed at anti-programmed cell death 1 (anti-PD1) or anti-programmed cell death ligand 1 (anti-PDL1)
• Have severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: XmAb18087 Monotherapy; Part A, will enroll participants with previously treated advanced MCC, consists of safety-run in cohorts followed by an expansion cohort.	Biological: XmAb18087; Monoclonal bispecific antibody
Experimental: Part B: XmAb18087 + pembrolizumab; Part B, will enroll participants with advanced MCC not previously treated with anti-programmed cell death 1 (PD1) or anti-programmed cell death ligand 1 (PDL1) agents, consists of safety run-in cohorts followed by an expansion cohort.	Drug: XmAb18087 ± Pembrolizumab; XmAb18087 ± Pembrolizumab
Experimental: Part C: XmAb18087 monotherapy; Part C will enroll participants with previously treated extensive-stage SCLC and consists of safety-run in cohorts followed by an expansion cohort.	Biological: XmAb18087; Monoclonal bispecific antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events	A treatment-emergent adverse event (TEAE) was any untoward medical occurrence in a participant treated with study drug. The TEAE does not necessarily have a causal relationship with this treatment. A TEAE can therefore be any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. TEAEs may include the onset of new illness and the exacerbation of preexisting conditions. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section."	Day 1 (after dosing) up to end of study (up to 163 days)
Overall Response Rate as Assessed by RECIST 1.1 Criteria		Up to end of study (up to 163 days)
Complete and Partial Response Rate as Assessed by RECIST 1.1 Criteria		Up to end of study (up to 163 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of Response	Up to end of study (up to 163 days)
Progression-free Survival as Assessed by Per RECIST 1.1 Criteria	Up to end of study (up to 163 days)
Overall Survival as Assessed by Per RECIST 1.1 Criteria	Up to end of study (up to 163 days)
Pharmacokinetics: Maximum Observed Serum Concentration	Predose up to end of study (up to 163 days)
Immunogenicity: Number of Participants With Anti-XmAb18087 Antibodies	Up to end of study (up to 163 days)

Collaborators and Investigators

• Sponsor: Xencor, Inc.
• Collaborators: ICON plc
• Investigators: Study Director: Benjamin Thompson, MD, PhD, Medical Director, Clinical Development, Xencor

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2021
• Primary Completion (Actual): March 24, 2022
• Study Completion (Actual): March 24, 2022

Study Registration Dates

• First Submitted: October 5, 2020
• First Submitted That Met QC Criteria: October 15, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): April 20, 2023
• Last Update Submitted That Met QC Criteria: March 30, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: SCLC; MCC
• Additional Relevant MeSH Terms: Virus Diseases; Infections; Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; DNA Virus Infections; Tumor Virus Infections; Neuroendocrine Tumors; Polyomavirus Infections; Carcinoma, Neuroendocrine; Lung Neoplasms; Carcinoma; Small Cell Lung Carcinoma; Carcinoma, Merkel Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab
• Other Study ID Numbers: XmAb18087-02; DUET 1-02 (Other Identifier: Xencor)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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