Clinical trial NCT03849469: A Study of XmAb®22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Xencor, Inc.
Sponsor class: INDUSTRY
Collaborators: name: ICON Clinical Research
First posted: 2019-02-21
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Safety and tolerability profile of XmAb22841 assessed by rates of treatment-related adverse events (AEs), graded by CTCAE v4.03.
timeFrame: 56 Days
Secondary outcomes:
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: UCSD Medical Center - Encinitas
state: California
city: La Jolla
country: United States
facility: Koman Family Outpatient Pavilion
state: California
city: La Jolla
country: United States
facility: UC San Diego Medical Center - La Jolla (Jacobs Medical Center / Thornton Pavilion)
state: California
city: La Jolla
country: United States
facility: UCSD Altman Clinical and Translational Research Institute Building (ACTRI)
state: California
city: La Jolla
country: United States
facility: UCSD Perlman Medical Offices
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology & Oncology Clinic
state: California
city: San Diego
country: United States
facility: UC San Diego Medical Center - Hillcrest
state: California
city: San Diego
country: United States
facility: UCSD Rancho Bernardo Medical Office
state: California
city: Vista
country: United States
facility: UCSD Medical Center - Vista
state: California
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Chestnut Hill
country: United States
facility: Brigham and Women's Health Care Center, Chestnut Hill
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical School
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Farmington Hills
country: United States
facility: Karmanos Cancer Institute Weisberg Cancer Treatment Center
state: Michigan
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center (Tisch Hospital)
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania - Perelman Center for Advanced Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Shadyside Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: Mary Crowley Cancer Research - Medical City
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah, Huntsman Cancer Institute
state: Utah
Study officials:
affiliation: Xencor, Inc.
name: Benjamin Thompson, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.