Clinical Trials /

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

NCT03752398

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Cervical Carcinoma
  • Colorectal Carcinoma
  • Endometrial Carcinoma
  • Gastric Adenocarcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Melanoma
  • Myxofibrosarcoma
  • Nasopharyngeal Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Carcinoma
  • Renal Cell Carcinoma
  • Sarcoma
  • Small Cell Lung Carcinoma
  • Soft Tissue Sarcoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: XmAb23104-01
  • SECONDARY ID: DUET-3
  • NCT ID: NCT03752398

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

Interventions

DrugSynonymsArms
XmAb®23104XmAb®23104 Combination Therapy with Ipilimumab
Yervoy® (ipilimumab)XmAb®23104 Combination Therapy with Ipilimumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
XmAb®23104 MonotherapyExperimentalXmAb®23104 administered by IV dosing on Days 1 and 15 of each 28-day cycle x 2 cycles
  • XmAb®23104
XmAb®23104 Combination Therapy with IpilimumabExperimentalXmAb®23104 administered by IV on Days 1 and 15 of each 28-day cycle x 2 cycles + Yervoy® (ipilimumab)
  • XmAb®23104
  • Yervoy® (ipilimumab)

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

             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

          3. All subjects' cancer must have progressed after treatment with standard/approved
             therapies or have no appropriate available therapies.

          4. Subjects must have measurable disease by RECIST 1.1.

          5. All subjects must have adequate archival tumor sample (slides or archival FFPE
             block[s] containing tumor.

          6. 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.

          7. 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Treatment-related adverse events as assessed by CTCAE v4.03
Time Frame:56 Days
Safety Issue:
Description:Safety and tolerability

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Xencor, Inc.

Trial 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

Last Updated

December 22, 2020