A Study of XmAb®23104 in Subjects With Selected Advanced Solid Tumors (DUET-3)

Hepatocellular Carcinoma Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03752398
• Other study ID #: XmAb23104-01
• Secondary ID: DUET-3
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 1, 2019
• Est. completion date: September 2025

Study information

• Verified date: February 2024
• Source: Xencor, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 300
• Est. completion date: September 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Breast Carcinoma That is Estrogen Receptor, Progesterone Receptor, and Her2 Negative
• Breast Neoplasms
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Cervical Carcinoma
• Colorectal Carcinoma
• Colorectal Neoplasms
• Endometrial Carcinoma
• Endometrial Neoplasms
• Gastric or Gastroesophageal Junction Adenocarcinoma
• Hepatocellular Carcinoma
• Histiocytoma, Malignant Fibrous
• Lung Neoplasms
• Melanoma
• Melanoma (Excluding Uveal Melanoma)
• Nasopharyngeal Carcinoma
• Non-small Cell Lung Carcinoma
• Pancreatic Carcinoma
• Pancreatic Neoplasms
• Renal Cell Carcinoma
• Sarcoma
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck
• Undifferentiated Pleomorphic Sarcoma
• Urothelial Carcinoma

Intervention

Biological:
• XmAb®23104
Monoclonal bispecific antibody
• Yervoy® (ipilimumab)
Monoclonal antibody

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	University of Colorado Hospital - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Emily Couric Clinical Cancer Center	Charlottesville	Virginia
United States	Mary Crowley Cancer Research - Medical City	Dallas	Texas
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	Duke Cancer Institute	Durham	North Carolina
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Columbia University Medical Center	New York	New York
United States	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Washington University School of Medicine Siteman Cancer Center	Saint Louis	Missouri
United States	University of Utah, Huntsman Cancer Institute	Salt Lake City	Utah
United States	UC San Diego Moores Cancer Center	San Diego	California
United States	Florida Cancer Specialists	Sarasota	Florida
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Xencor, Inc.	ICON plc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-related adverse events as assessed by CTCAE v4.03	Safety and tolerability	56 Days