Clinical Trials /

A Study of XmAb®20717 in Subjects With Selected Advanced Solid Tumors

NCT03517488

Description:

This is a Phase 1, multiple dose, ascending dose escalation study to define a MTD/RD and regimen of XmAb20717, to describe safety and tolerability, to assess PK and immunogenicity, and to preliminarily assess anti-tumor activity of XmAb20717 in subjects with selected advanced solid tumors.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Adnexal Carcinoma
  • Anal Squamous Cell Carcinoma
  • Basal Cell Carcinoma
  • Breast Carcinoma
  • Cervical Carcinoma
  • Cholangiocarcinoma
  • Colorectal Carcinoma
  • Endometrial Carcinoma
  • Fallopian Tube Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Malignant Solid Tumor
  • Melanoma
  • Mesothelioma
  • Nasopharyngeal Carcinoma
  • Neuroendocrine Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Prostate Adenocarcinoma
  • Renal Cell Carcinoma
  • Salivary Gland Carcinoma
  • Small Cell Lung Carcinoma
  • Squamous Cell Carcinoma of the Penis
  • Thymic Carcinoma
  • Thymoma
  • Urothelial Carcinoma
  • Vulvar Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of XmAb®20717 in Subjects With Selected Advanced Solid Tumors
  • Official Title: A Phase 1 Multiple Dose Study to Evaluate the Safety and Tolerability of XmAb®20717 in Subjects With Selected Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: XmAb20717-01
  • SECONDARY ID: DUET-2
  • NCT ID: NCT03517488

Conditions

  • Melanoma
  • Breast Carcinoma
  • Hepatocellular Carcinoma
  • Urothelial Carcinoma
  • Squamous Cell Carcinoma of the Head and Neck
  • Renal Cell Carcinoma
  • Colorectal Carcinoma
  • Non-small Cell Lung Carcinoma
  • Gastric or Gastroesophageal Junction Adenocarcinoma
  • Endometrial Carcinoma
  • Mesothelioma
  • Neuroendocrine Carcinoma
  • Cervical Cancer
  • Small Cell Lung Carcinoma
  • Squamous Cell Carcinoma of the Anus
  • Castration-Resistant Prostate Carcinoma
  • Nasopharyngeal Carcinoma
  • Cholangiocarcinoma
  • Basal Cell Carcinoma
  • Ovarian Carcinoma
  • Fallopian Tube Carcinoma
  • Thymoma
  • Thymic Carcinoma
  • Squamous Cell Carcinoma of the Penis
  • Vulvar Carcinoma
  • Solid Tumors With Published Evidence of Anti-tumor Activity With Anti-PD1/PDL1 and/or Anti-CTLA4-directed Therapy
  • Malignant Adnexal Neoplasms
  • Non-squamous Cell Salivary Gland Carcinoma

Interventions

DrugSynonymsArms
XmAb20717XmAb20717

Purpose

This is a Phase 1, multiple dose, ascending dose escalation study to define a MTD/RD and regimen of XmAb20717, to describe safety and tolerability, to assess PK and immunogenicity, and to preliminarily assess anti-tumor activity of XmAb20717 in subjects with selected advanced solid tumors.

Trial Arms

NameTypeDescriptionInterventions
XmAb20717ExperimentalXmAb20717 administered by intravenous dosing on Days 1 and 15 of each 28-day cycle for a total of two cycles
  • XmAb20717

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed diagnosis of one of the following advanced
             solid tumors:

        PART A (Dose Escalation Cohorts)

          1. Melanoma;

          2. Breast carcinoma that is estrogen receptor, progesterone receptor, and Her2 negative
             (triple-negative breast cancer; TNBC);

          3. Hepatocellular carcinoma;

          4. Urothelial carcinoma;

          5. Squamous cell carcinoma of the head and neck;

          6. Renal cell carcinoma (clear cell predominant type);

          7. Microsatellite instability-high or mismatch repair deficient colorectal carcinoma or
             endometrial carcinoma;

          8. Non-small cell lung carcinoma;

          9. Gastric or gastroesophageal junction adenocarcinoma

         10. Mesothelioma;

         11. High-grade neuroendocrine carcinoma, including small cell carcinoma of the lung

         12. Cervical cancer;

         13. Squamous cell carcinoma of the anus

        PART B (Dose Expansion Cohorts):

          1. Melanoma

          2. Renal cell carcinoma (clear cell predominant type)

          3. Non-small cell lung carcinoma

          4. Castrate-resistant adenocarcinoma of the prostate, defined as progressive disease
             after surgical castration, or progression in the setting of medical androgen ablation
             with a castrate level of testosterone (< 50 ng/dL)

          5. Nasopharyngeal carcinoma

          6. Cholangiocarcinoma

          7. Basal cell carcinoma

          8. Squamous cell carcinoma of the anus

          9. Mesothelioma

         10. Ovarian or fallopian tube carcinoma

         11. Malignant adnexal neoplasms (including, but not limited to, sebaceous carcinoma,
             trichilemmal carcinoma, pilomatrix carcinoma, eccrine carcinoma, hidradenocarcinoma,
             adnexal carcinoma with divergent differentiation, papillary digital eccrine
             adenocarcinoma, microcystic adnexal carcinoma, and clear cell eccrine carcinoma)

         12. Thymoma

         13. Thymic carcinoma

         14. Squamous cell carcinoma of the penis

         15. Neuroendocrine carcinoma

         16. Vulvar cancer

         17. Non-squamous cell salivary gland carcinoma (except adenoid cystic carcinoma)

         18. Subjects with other solid tumors for which there is published evidence of anti-tumor
             activity with anti-PD1/PDL1 and/or anti-CTLA4-directed therapy but for which there is
             no FDA-approved anti-PD1/PDL1 or CTLA4-directed checkpoint inhibitor treatment may be
             eligible for Part B after approval by the Medical Monitor.

               -  All subjects' cancer must have progressed after treatment with all standard
                  therapies or have no appropriate available therapies.

               -  Subjects, except those with adenocarcinoma of the prostate, must have measurable
                  disease by RECIST 1.1.

               -  Have available adequate archival formalin-fixed paraffin-embedded block(s)/slides
                  containing tumor or adequate pre-dose fresh tumor biopsy tissue

               -  ECOG performance status of 0 - 1

               -  Subjects with adenocarcinoma of the prostate must have evaluable disease
                  (measurable or nonmeasurable lesions) by PCWG3.

        Exclusion Criteria:

          -  Subjects currently receiving other anticancer therapies, with the exception of
             subjects with adenocarcinoma of the prostate, who may continue luteinizing
             hormone-releasing hormone (LHRH) analogue therapy.

          -  Treatment with any CTLA4 antibody within 6 weeks of the start of study drug.

          -  Treatment with nivolumab or any PDL1 or PDL2-directed antibody within 4 weeks of the
             start of study drug.

          -  Treatment with pembrolizumab within 4 - 12 weeks of the start of study drug (cohort
             dependent).

          -  Treatment with any other anticancer therapy within 2 weeks of the start of study drug
             (i.e., other immunotherapy, chemotherapy, radiation therapy, etc.). Subjects with
             prostate cancer may continue LHRH analogue therapy.

          -  A life-threatening (Grade 4) immune-mediated AE related to prior immunotherapy.

          -  Failure to recover from any immune-related toxicity from prior cancer therapy to ≤
             Grade 1, except if previous immune-related endocrinopathy is medically managed with
             hormone replacement therapy only.

          -  Failure to recover from any other toxicity (other than immune-related toxicity)
             related to previous anticancer treatment to ≤ Grade 2.

          -  Have known active CNS metastases and/or carcinomatous meningitis. Participants 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, are clinically stable, and without requirement of steroid treatment for at
             least 14 days prior to first dose of study treatment.

          -  Active known or suspected autoimmune disease (except that subjects are permitted to
             enroll if they have vitiligo; type 1 diabetes mellitus or 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).

          -  Has any condition requiring systemic treatment with corticosteroids, prednisone
             equivalents, or other immunosuppressive medications within 14 days prior to first dose
             of study drug (except that inhaled or topical corticosteroids or brief courses of
             corticosteroids given for prophylaxis of contrast dye allergic response are
             permitted).

          -  Receipt of an organ allograft.

          -  Prior treatment with any checkpoint inhibitor therapy regimen that targets both PD1/L1
             and CTLA-4.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine the safety and tolerability profile of XmAb20717
Time Frame:56 Days
Safety Issue:
Description:Treatment-related adverse events as assessed by CTCAE v4.03

Details

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

Trial Keywords

  • DUET-2
  • Melanoma
  • Triple Negative Breast Cancer
  • Hepatocellular Cancer
  • Urothelial Cancer
  • Renal Cell Cancer
  • Head and Neck Cancer
  • MSI-high Colorectal Cancer
  • MSI-high Endometrial Cancer
  • Non-small Cell Lung Cancer
  • Gastric Cancer
  • Gastroesophageal Junction Cancer
  • Mesothelioma
  • High-grade Neuroendocrine Cancer
  • Cervical Cancer
  • Small Cell Lung Cancer
  • Anal Cancer
  • Prostate Cancer
  • Nasopharyngeal Cancer
  • Bile Duct Cancer
  • Basal Cell Skin Cancer
  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Malignant Adnexal Tumor
  • Thymus Cancer
  • Penile Cancer
  • Vulvar Cancer
  • Salivary Gland Cancer

Last Updated

May 12, 2020