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

Status: Active

Description

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.

Eligibility Criteria

Inclusion Criteria

  • 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 (excluding uveal 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
  • Microsatellite instability-high or mismatch repair deficient tumors
  • 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.

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, and 4P; and within 3 weeks for Cohorts 6M, 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.

Locations & Contacts

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: Approved
Contact: Louis Slonlker
Phone: 310-794-8582
Email: LSloniker@mednet.ucla.edu

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: Active
Name Not Available

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: Active
Name Not Available

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Name Not Available

New York

New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Name Not Available

Texas

Houston
M D Anderson Cancer Center
Status: Active
Contact: Shubham Pant
Phone: 713-745-6601
Email: spant@mdanderson.org

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Name Not Available

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Xencor, Inc.

Trial IDs

Primary ID XmAb22841-01
Secondary IDs NCI-2019-02498, DUET-4
Clinicaltrials.gov ID NCT03849469