A Study of XmAb®22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors (DUET-4)

March 29, 2023 updated by: Xencor, Inc.

A Phase 1 Multiple-Dose Study to Evaluate the Safety and Tolerability of XmAb®22841 Monotherapy and in Combination With Pembrolizumab in Subjects With Selected Advanced Solid Tumors (DUET-4)

This is a Phase 1, multiple dose, ascending-dose escalation study and expansion study designed to define a maximum tolerated dose and/or recommended dose of XmAb22841 monotherapy and in combination with pembrolizumab; to assess safety, tolerability, pharmacokinetics, immunogenicity, and anti-tumor activity of XmAb22841 monotherapy and in combination with pembrolizumab in subjects with select advanced solid tumors.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

78

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Encinitas, California, United States, 92024
        • UCSD Medical Center - Encinitas
      • La Jolla, California, United States, 92093
        • UC San Diego Moores Cancer Center
      • La Jolla, California, United States, 92037
        • Koman Family Outpatient Pavilion
      • La Jolla, California, United States, 92037
        • UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion)
      • La Jolla, California, United States, 92037
        • UCSD Altman Clinical and Translational Research Institute Building (ACTRI)
      • La Jolla, California, United States, 92037
        • UCSD Perlman Medical Offices
      • Los Angeles, California, United States, 90095
        • UCLA Hematology & Oncology Clinic
      • San Diego, California, United States, 92103
        • UC San Diego Medical Center - Hillcrest
      • San Diego, California, United States, 92127
        • UCSD Rancho Bernardo Medical Office
      • Vista, California, United States, 92081
        • UCSD Medical Center - Vista
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute, Emory University
      • Atlanta, Georgia, United States, 30308
        • Emory University Hospital Midtown
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospital and Clinics
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Chestnut Hill, Massachusetts, United States, 02467
        • Brigham and Women's Health Care Center, Chestnut Hill
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Medical School
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
      • Farmington Hills, Michigan, United States, 48334
        • Karmanos Cancer Institute Weisberg Cancer Treatment Center
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10016
        • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
      • New York, New York, United States, 10016
        • NYU Langone Medical Center (Tisch Hospital)
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania - Perelman Center for Advanced Medicine
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Hillman Cancer Center
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Shadyside Hospital
    • Texas
      • Dallas, Texas, United States, 75230
        • Mary Crowley Cancer Research - Medical City
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • University of Utah, Huntsman Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

PART A (Dose Escalation Cohorts)

  1. All subjects' cancer must have progressed after treatment with all available therapies that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment.
  2. All subjects must have adequate archival tumor, or give consent to a fresh tumor biopsy.
  3. Subjects have an ECOG performance status of 0-1.

  4. Subjects in monotherapy and combination therapy cohorts must have histologically or cytologically confirmed advanced or metastatic solid tumors, including the following:

    1. Melanoma
    2. Cervical carcinoma
    3. Pancreatic carcinoma
    4. Breast carcinoma that is estrogen receptor, progesterone receptor, and Her2 negative (TNBC)
    5. Hepatocellular carcinoma
    6. Urothelial carcinoma
    7. Squamous cell carcinoma of the head and neck (HNSCC)
    8. Nasopharyngeal carcinoma (NPC)
    9. Renal cell carcinoma
    10. Colorectal carcinoma or endometrial carcinoma
    11. Small cell lung carcinoma or NSCLC
    12. Gastric or gastroesophageal junction adenocarcinoma
    13. Prostate adenocarcinoma
    14. Epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
    15. Intrahepatic cholangiocarcinoma

  5. Subjects in the combination cohorts in Part A with XmAb22841 and pembrolizumab may have an advanced solid tumor that either:

    • has progressed after treatment with all available therapies that are known to confer clinical benefit, or is intolerant or has refused standard treatment (as for the XmAb22841 monotherapy cohorts), or
    • is of a tumor type for which pembrolizumab is an approved indication and has not previously been treated with an agent targeting PD1 or PDL1.

PART B (Dose Expansion Cohorts)

XmAb22841 Single Agent Cohort

1. Must have histologically or cytologically confirmed advanced or metastatic solid tumor that has progressed after treatment with all available therapies that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment. Eligible tumor types include the following:

  1. Anti-PD1 refractory melanoma (or any uveal melanoma)
  2. Anti-PD1 refractory NSCLC
  3. Anti-PD1 refractory renal cell carcinoma (with clear cell component)
  4. Anti-PD1 refractory urothelial carcinoma
  5. Head and neck squamous cell carcinoma
  6. Hepatocellular carcinoma
  7. Gastric adenocarcinoma
  8. Cervical carcinoma
  9. Breast carcinoma that is estrogen receptor, progesterone receptor, and HER2 negative (TNBC)
  10. Epithelial ovarian cancer
  11. Nasopharyngeal carcinoma
  12. Squamous cell anal carcinoma
  13. Squamous cell penile carcinoma
  14. Squamous cell vulvar carcinoma

XmAb22841 + Pembrolizumab Cohorts

  1. Anti-PD-1 refractory melanoma (excluding uveal melanoma)
  2. Anti-PD-1 naïve melanoma (excluding uveal melanoma)
  3. Anti-PD-1 refractory NSCLC

  4. Anti-PD1 naïve NSCLC

    a. Must be PD-L1 high (TPS ≥ 50%), with no EGFR or ALK aberrations

  5. Anti-PD1 naïve urothelial carcinoma

    1. Must be PDL1 positive (CPS of ≥ 10), or ineligible for any platinum-containing chemotherapy regardless of PDL1 status; or
    2. Had disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy

Exclusion Criteria:

  1. Prior treatment with an investigational anti-LAG3 therapy.
  2. Treatment with any CTLA4 antibody within 16 weeks of the start of study drug for Cohorts 1M, 2M, 3M, 1P, and 2P; within 8 weeks for Cohorts 4M, 5M, 3P, 4P and 4Pi; and within 3 weeks for Cohorts 6M, 7Mi, 7M, 5P, and 6P.
  3. Systemic antineoplastic therapy, unconjugated antibody therapy within 4 weeks of the first dose of study treatment; or radiotherapy within 2 weeks of the first dose of study treatment; or small molecule kinase inhibitors within 6 elimination half-lives of the first dose of study treatment.
  4. Have received prior therapy with an anti-PD1, anti-PDL1, or anti PDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA4, OX 40, CD137) AND were permanently discontinued from that treatment due to an irAE.
  5. Failure to recover from any irAE from prior cancer therapy to Grade ≤ 1.
  6. Failure to recover from any other toxicity (other than immune-related toxicity) related to previous anticancer treatment to Grade ≤ 2.
  7. Active known or suspected autoimmune disease (except that subjects are permitted to enroll if they have vitiligo; type 1 diabetes mellitus; residual hypothyroidism due to an autoimmune condition that is treatable with hormone replacement therapy only; psoriasis, atopic dermatitis, or another autoimmune skin condition that is managed without systemic therapy; or arthritis that is managed without systemic therapy beyond oral acetaminophen and non-steroidal anti-inflammatory drugs).
  8. Receipt of an organ allograft.
  9. Treatment with antibiotics within 14 days prior to first dose of study drug.
  10. Participants with known HIV.
  11. Participants with known chronic hepatitis B virus (HBV) infection treated for less than 3 months prior to study enrollment and/or with a detectable HBV viral load; or hepatitis C virus (HCV) infection that has been treated for less than 4 weeks prior to study enrollment and/or with a detectable HCV viral load; or active HBV/HCV coinfection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1
Arm 1: XmAb®22841 Monotherapy
Biological: XmAb®22841
Monoclonal bispecific antibody
Experimental: Arm 2
Arm 2: Combination of XmAb®22841 and Pembrolizumab (Keytruda®)
Biological: XmAb®22841
Monoclonal bispecific antibody
Biological: Pembrolizumab (Keytruda®)
FDA-approved humanized monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability profile of XmAb22841 assessed by rates of treatment-related adverse events (AEs), graded by CTCAE v4.03.
Time Frame: 56 Days
Rates of treatment-related adverse events (AEs), graded by CTCAE v4.03, and additionally categorized as either immune-related or non-immune AEs.
56 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xencor, Inc.

Collaborators

ICON Clinical Research

Investigators

  • Study Director: Benjamin Thompson, MD, PhD, Xencor, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 29, 2019

Primary Completion (Actual)

February 16, 2023

Study Completion (Actual)

February 16, 2023

Study Registration Dates

First Submitted

February 19, 2019

First Submitted That Met QC Criteria

February 19, 2019

First Posted (Actual)

February 21, 2019

Study Record Updates

Last Update Posted (Actual)

March 30, 2023

Last Update Submitted That Met QC Criteria

March 29, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XmAb22841-01
  • DUET-4 (Other Identifier: Xencor, Inc.)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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