Clinical trial NCT03752398: A Study of XmAb®23104 in Subjects With Selected Advanced Solid Tumors (DUET-3)
Official title: A Phase 1 Multiple-Dose Study to Evaluate the Safety and Tolerability of XmAb®23104 in Subjects With Selected Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma (Excluding Uveal Melanoma)
Cervical Carcinoma
Pancreatic Carcinoma
Breast Carcinoma That is Estrogen Receptor, Progesterone Receptor, and Her2 Negative
Hepatocellular Carcinoma
Urothelial Carcinoma
Squamous Cell Carcinoma of the Head and Neck
Nasopharyngeal Carcinoma
Renal Cell Carcinoma
Colorectal Carcinoma
Endometrial Carcinoma
Non-small Cell Lung Carcinoma
Small Cell Lung Cancer
Gastric or Gastroesophageal Junction Adenocarcinoma
Advanced Solid Tumors
Undifferentiated Pleomorphic Sarcoma
Keywords: DUET-3
Advanced solid tumors
Melanoma
Cervical Cancer
Pancreatic Cancer
Triple Negative Breast Cancer
Hepatocellular/Liver Cancer
Urothelial Cancer
Bladder Cancer
Renal Cell Cancer
Head and Neck Cancer
Colorectal Cancer
Endometrial Cancer
Non-small Cell Lung Cancer
Small Cell Lung Cancer
Gastric Cancer
Gastroesophageal Junction Cancer
Sarcoma
Lead sponsor: Xencor, Inc.
Sponsor class: INDUSTRY
Collaborators: name: ICON plc
First posted: 2018-11-26
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, multiple dose, ascending dose escalation study to define a MTD/RD and regimen of XmAb23104, to describe safety and tolerability, to assess PK and immunogenicity, and to preliminarily assess anti-tumor activity of XmAb23104 monotherapy and combination therapy with ipilimumab in subjects with selected advanced solid tumors.


Eligibility criteria: Inclusion Criteria:

1. Subjects in Part A (dose escalation) must have a diagnosis of any of the following:

   Histologically or cytologically confirmed advanced solid tumors, including the following:
   1. Melanoma (excluding uveal melanoma)
   2. Cervical carcinoma
   3. Pancreatic carcinoma
   4. Breast carcinoma that is estrogen receptor, progesterone receptor, and Her2 negative
   5. Hepatocellular carcinoma
   6. Urothelial carcinoma
   7. Squamous cell carcinoma of the head and neck
   8. Nasopharyngeal carcinoma
   9. Renal cell carcinoma
   10. Colorectal carcinoma
   11. Endometrial carcinoma
   12. NSCLC
   13. Small cell lung cancer
   14. Gastric or gastroesophageal junction adenocarcinoma
   15. Sarcoma
2. Subjects in Part B (expansion) must have a diagnosis of any of the following:

   Histologically or cytologically confirmed advanced solid tumors of the following types:
   1. Non-squamous NSCLC
   2. Melanoma
   3. HNSCC, including NPC
   4. CRC
   5. UPS, including other select high grade STS, such as MFS
   6. ccRCC

   Prior to enrolling into Part B (expansion), subjects should have received disease-specific standard therapy as indicated for:
   1. Non-squamous NSCLC
   2. Melanoma
   3. HNSCC, including NPC
   4. CRC
   5. UPS, including other select high-grade STS such as MFS
   6. RCC, clear cell histology (ccRCC)
3. Subjects in Part C (expansion)must have a diagnosis of MSS or proficient mismatch repair CRC with the following:

   1. cancer must have progressed after treatment with standard/approved therapies or have no appropriate available therapies
   2. subjects will have life expectancy greater than 3 months
4. All subjects' cancer must have progressed after treatment with standard/approved therapies or have no appropriate available therapies.
5. Subjects must have measurable disease by RECIST 1.1.
6. All subjects must have adequate archival tumor sample (slides or archival FFPE block\[s\] containing tumor.
7. All subjects in Part B (dose expansion) must have a tumor lesion that can be biopsied at acceptable risk (in the judgment of the Investigator) and must agree to both a fresh biopsy during screening and a second biopsy following treatment.
8. Subjects have an ECOG performance status of 0-1.

Exclusion Criteria:

1. Currently receiving other anticancer therapies
2. Prior treatment with an investigational anti-ICOS therapy
3. Treatment with any PDL1 or PDL2-directed therapy within 4 weeks of the start of study drug
4. Treatment with nivolumab within 4 weeks of the start of study drug
5. Treatment with pembrolizumab within 24 weeks of start of study drug for Cohorts 1A - 10A
6. Treatment with any other anticancer therapy within 2 weeks of the start of study drug (ie, other immunotherapy, chemotherapy, radiation therapy, etc.)
7. A life-threatening (Grade 4) irAE related to prior immunotherapy
8. Failure to recover from any irAE from prior cancer therapy to Grade ≤ 1, except for endocrinopathies that are on stable hormone replacement doses
9. Failure to recover from any other toxicity (other than immune-related toxicity) related to previous anticancer treatment to Grade ≤ 2
10. Known active central nervous system involvement by malignant disease. Subjects with previously treated brain metastases may participate provided they are radiologically stable, ie, are without evidence of progression for at least 4 weeks by repeat imaging and are clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
11. Active known or suspected autoimmune disease
12. Receipt of an organ allograft
13. History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease (including, but not limited to, cardiopulmonary, renal, metabolic, hematologic or psychiatric) other than their primary malignancy, that in the opinion of the Investigator would pose a risk to patient safety or interfere with study evaluations, procedures, or completion
14. Treatment with antibiotics within 14 days prior to first dose of study drug
15. Receipt of a live-virus vaccine within 30 days prior to first dose of study drug (seasonal flu vaccines that do not contain live virus are permitted).
16. Treatment with ipilimumab within 4 weeks of the start of study drug

Primary outcomes:
measure: Treatment-related adverse events as assessed by CTCAE v4.03
timeFrame: 56 Days
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion
state: Colorado
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine Siteman Cancer Center
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Abramson Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
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
city: Charlottesville
country: United States
facility: Emily Couric Clinical Cancer Center
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
Study officials:
affiliation: Xencor, Inc.
name: Chet Bohac, MD, MSc
role: STUDY_DIRECTOR
References: