A Study of XmAb®22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors

NCT03849469 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: XmAb22841-01DUET-4
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 28

Brief Summary

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.

Conditions

Melanoma; Cervical Carcinoma; Pancreatic Carcinoma; Triple Negative Breast Cancer; Hepatocellular Carcinoma; Urothelial Carcinoma; Squamous Cell Carcinoma of the Head and Neck; Nasopharyngeal Carcinoma; Renal Cell Carcinoma; Non-small Cell Lung Carcinoma; Small Cell Lung Carcinoma; Gastric or Gastroesophageal Junction Adenocarcinoma; Advanced or Metastatic Solid Tumors; Prostate Carcinoma; Epithelial Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma; Intrahepatic Cholangiocarcinoma; Squamous Cell Anal Cancer; Squamous Cell Penile Carcinoma; Squamous Cell Vulvar Carcinoma; Colorectal Carcinoma; Endometrial Carcinoma

Keywords

DUET-4; Advanced solid tumors; Metastatic solid tumors; Melanoma; Cervical Cancer; Pancreatic Cancer; Triple Negative Breast Cancer; Hepatocellular/Liver Cancer; Urothelial Cancer; Renal Cell Cancer; Squamous Cell Carcinoma of the Head and Neck; Non-small Cell Lung Cancer; Small Cell Lung Cancer; Gastric Cancer; Gastroesophageal Junction Cancer; Lymphocyte-activation gene 3 (LAG3); Cytotoxic T-lymphocyte-associated protein 4 (CTLA4); Prostate Cancer; Nasopharyngeal carcinoma; Epithelial ovarian cancer; Fallopian tube cancer; Primary peritoneal carcinoma; Intrahepatic cholangiocarcinoma; Squamous Cell Anal Carcinoma; Squamous Cell Penile Carcinoma; Squamous Cell Vulvar Carcinoma; Colorectal Carcinoma; Endometrial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability profile of XmAb22841 assessed by rates of treatment-related adverse events (AEs), graded by CTCAE v4.03.

  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

Study Arms (2)

Arm 1

EXPERIMENTAL

Arm 1: XmAb®22841 Monotherapy

Biological: XmAb®22841

Arm 2

EXPERIMENTAL

Arm 2: Combination of XmAb®22841 and Pembrolizumab (Keytruda®)

Biological: XmAb®22841; Biological: Pembrolizumab (Keytruda®)

Interventions

XmAb®22841 BIOLOGICAL

Monoclonal bispecific antibody

Arm 1; Arm 2

Pembrolizumab (Keytruda®) BIOLOGICAL

FDA-approved humanized monoclonal antibody

Arm 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PART A (Dose Escalation Cohorts)
• 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.
• All subjects must have adequate archival tumor, or give consent to a fresh tumor biopsy.
• Subjects have an ECOG performance status of 0-1.
• Subjects in monotherapy and combination therapy cohorts must have histologically or cytologically confirmed advanced or metastatic solid tumors, including the following:
• Melanoma
• Cervical carcinoma
• Pancreatic carcinoma
• Breast carcinoma that is estrogen receptor, progesterone receptor, and Her2 negative (TNBC)
• Hepatocellular carcinoma
• Urothelial carcinoma
• Squamous cell carcinoma of the head and neck (HNSCC)
• Nasopharyngeal carcinoma (NPC)
• Renal cell carcinoma
• Colorectal carcinoma or endometrial carcinoma

You may not qualify if:

• Prior treatment with an investigational anti-LAG3 therapy.
• 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.
• 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.
• 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.
• Failure to recover from any irAE from prior cancer therapy to Grade ≤ 1.
• Failure to recover from any other toxicity (other than immune-related toxicity) related to previous anticancer treatment to Grade ≤ 2.
• 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).
• Receipt of an organ allograft.
• Treatment with antibiotics within 14 days prior to first dose of study drug.
• Participants with known HIV.
• 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.

Sponsors & Collaborators

• Xencor, Inc.: lead
• ICON Clinical Research: collaborator

Study Sites (28)

UCSD Medical Center - Encinitas

Encinitas, California, 92024, United States

Location

Koman Family Outpatient Pavilion

La Jolla, California, 92037, United States

Location

UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion)

La Jolla, California, 92037, United States

Location

UCSD Altman Clinical and Translational Research Institute Building (ACTRI)

La Jolla, California, 92037, United States

Location

UCSD Perlman Medical Offices

La Jolla, California, 92037, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

UCLA Hematology & Oncology Clinic

Los Angeles, California, 90095, United States

Location

UC San Diego Medical Center - Hillcrest

San Diego, California, 92103, United States

Location

UCSD Rancho Bernardo Medical Office

San Diego, California, 92127, United States

Location

UCSD Medical Center - Vista

Vista, California, 92081, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

University of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Brigham and Women's Health Care Center, Chestnut Hill

Chestnut Hill, Massachusetts, 02467, United States

Location

University of Michigan Medical School

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Karmanos Cancer Institute Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334, United States

Location

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

Location

NYU Langone Medical Center (Tisch Hospital)

New York, New York, 10016, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Hospital of the University of Pennsylvania - Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

UPMC Shadyside Hospital

Pittsburgh, Pennsylvania, 15232, United States

Location

Mary Crowley Cancer Research - Medical City

Dallas, Texas, 75230, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Wong RL, Yu EY. Refining Immuno-Oncology Approaches in Metastatic Prostate Cancer: Transcending Current Limitations. Curr Treat Options Oncol. 2021 Jan 12;22(2):13. doi: 10.1007/s11864-020-00808-x.

  PMID: 33433743 DERIVED

MeSH Terms

Conditions

Melanoma; Uterine Cervical Neoplasms; Pancreatic Neoplasms; Triple Negative Breast Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Transitional Cell; Squamous Cell Carcinoma of Head and Neck; Nasopharyngeal Carcinoma; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Prostatic Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Cholangiocarcinoma; Anus Neoplasms; Colorectal Neoplasms; Endometrial Neoplasms; Liver Neoplasms; Stomach Neoplasms; Diabetes Mellitus, Insulin-Dependent, 12

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Breast Neoplasms; Breast Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Liver Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Ovarian Neoplasms; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Fallopian Tube Diseases; Rectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases; Colonic Diseases; Stomach Diseases

Study Officials

• Benjamin Thompson, MD, PhD

  Xencor, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2019
• First Posted: February 21, 2019
• Study Start: May 29, 2019
• Primary Completion: February 16, 2023
• Study Completion: February 16, 2023
• Last Updated: March 30, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (28)