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

Phase 1

Completed

• Conditions: Hepatocellular Carcinoma; Urothelial Carcinoma; Colorectal Carcinoma; Pancreatic Carcinoma; Breast Carcinoma That is Estrogen Receptor, Progesterone Receptor, and Her2 Negative; Melanoma (Excluding Uveal Melanoma); Cervical Carcinoma; Nasopharyngeal Carcinoma; Renal Cell Carcinoma; Non-small Cell Lung Carcinoma
• Interventions: Biological: XmAb®23104; Biological: Yervoy® (ipilimumab)

• Registration Number: NCT03752398
• Lead Sponsor: Xencor, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-11-20
• Study First Submitted QC: 2018-11-23
• Study First Posted: 2018-11-26
• Study Start: 2019-05-01
• Primary Completion: 2024-02-15
• Study Completion: 2024-02-15
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-02
• Last Update Posted: 2024-07-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 198

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
XmAb®23104 Combination Therapy with Ipilimumab	XmAb®23104	XmAb®23104 administered by IV on Days 1 and 15 of each 28-day cycle x 2 cycles + Yervoy® (ipilimumab)
XmAb®23104 Monotherapy	XmAb®23104	XmAb®23104 administered by IV dosing on Days 1 and 15 of each 28-day cycle x 2 cycles
XmAb®23104 Combination Therapy with Ipilimumab	Yervoy® (ipilimumab)	XmAb®23104 administered by IV on Days 1 and 15 of each 28-day cycle x 2 cycles + Yervoy® (ipilimumab)

Primary Outcome Measures

Name	Time	Method
Treatment-related adverse events as assessed by CTCAE v4.03	56 Days	Safety and tolerability

Trial Locations

Locations (18)

Florida Cancer Specialists; 🇺🇸 Sarasota, Florida, United States

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, 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

Emory University; 🇺🇸 Atlanta, Georgia, United States

UPMC Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Washington University School of Medicine Siteman Cancer Center; 🇺🇸 Saint Louis, Missouri, United States

Mary Crowley Cancer Research - Medical City; 🇺🇸 Dallas, Texas, United States

Emily Couric Clinical Cancer Center; 🇺🇸 Charlottesville, Virginia, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Duke Cancer Institute; 🇺🇸 Durham, North Carolina, United States

University of Utah, Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States

Sarah Cannon Research Institute at HealthONE; 🇺🇸 Denver, Colorado, United States

Providence Portland Medical Center; 🇺🇸 Portland, Oregon, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

University of Colorado Hospital - Anschutz Cancer Pavilion; 🇺🇸 Aurora, Colorado, United States

University of Pennsylvania Abramson Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

UC San Diego Moores Cancer Center; 🇺🇸 San Diego, California, United States