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

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)

INTRODUCTION

  • Org Study ID: XmAb22841-01
  • Secondary ID: DUET-4
  • NTC ID: NCT03849469
  • Sponsor: Xencor, Inc.

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.

  • Overall Status
    Recruiting
  • Start Date
    May 29, 2019
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Safety and tolerability profile of XmAb22841 assessed by rates of treatment-related adverse events (AEs), graded by CTCAE v4.03.

Primary Outcome 1 - Timeframe: 56 Days

CONDITION

  • 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

ELIGIBILITY

Inclusion Criteria:
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

- Small cell lung carcinoma or NSCLC

- Gastric or gastroesophageal junction adenocarcinoma

- Prostate adenocarcinoma

- Epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer

- Intrahepatic cholangiocarcinoma
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:
Anti-PD1 refractory melanoma (or any uveal melanoma)

- Anti-PD1 refractory NSCLC

- Anti-PD1 refractory renal cell carcinoma (with clear cell component)

- Anti-PD1 refractory urothelial carcinoma

- Head and neck squamous cell carcinoma

- Hepatocellular carcinoma

- Gastric adenocarcinoma

- Cervical carcinoma

- Breast carcinoma that is estrogen receptor, progesterone receptor, and HER2 negative (TNBC)

- Epithelial ovarian cancer

- Nasopharyngeal carcinoma

- Squamous cell anal carcinoma

- Squamous cell penile carcinoma

- Squamous cell vulvar carcinoma
XmAb22841 + Pembrolizumab Cohorts
Anti-PD-1 refractory melanoma (excluding uveal melanoma)

- Anti-PD-1 naïve melanoma (excluding uveal melanoma)

- Anti-PD-1 refractory NSCLC
Anti-PD1 naïve NSCLC
a. Must be PD-L1 high (TPS ≥ 50%), with no EGFR or ALK aberrations
Anti-PD1 naïve urothelial carcinoma
Must be PDL1 positive (CPS of ≥ 10), or ineligible for any platinum-containing chemotherapy regardless of PDL1 status; or

- Had disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
Exclusion Criteria:
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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Benjamin Thompson, MD, PhD

Role: Study Director

Affiliation: Xencor, Inc.

Overall Contact

Name: Benjamin Thompson, MD, PhD

Phone: 619-517-7381, 858-245-9419

Email: bthompson@xencor.com, asarot@xencor.com

LOCATION

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