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A Study of XmAb®22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors (DUET-4)

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ClinicalTrials.gov Identifier: NCT03849469
Recruitment Status : Recruiting
First Posted : February 21, 2019
Last Update Posted : August 18, 2021
Sponsor:
Collaborator:
ICON Clinical Research
Information provided by (Responsible Party):
Xencor, Inc.

Brief Summary:
This is a Phase 1, multiple dose, ascending-dose escalation study and expansion study designed to define a maximum tolerated dose and/or recommended dose of XmAb22841 monotherapy and in combination with pembrolizumab; to assess safety, tolerability, pharmacokinetics, immunogenicity, and anti-tumor activity of XmAb22841 monotherapy and in combination with pembrolizumab in subjects with select advanced solid tumors.

Condition or disease Intervention/treatment Phase
Melanoma Cervical Carcinoma Pancreatic Carcinoma Triple Negative Breast Cancer Hepatocellular Carcinoma Urothelial Carcinoma Squamous Cell Carcinoma of the Head and Neck Nasopharyngeal Carcinoma Renal Cell Carcinoma Non-small Cell Lung Carcinoma Small Cell Lung Carcinoma Gastric or Gastroesophageal Junction Adenocarcinoma Advanced or Metastatic Solid Tumors Prostate Carcinoma Epithelial Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Carcinoma Intrahepatic Cholangiocarcinoma Squamous Cell Anal Cancer Squamous Cell Penile Carcinoma Squamous Cell Vulvar Carcinoma Colorectal Carcinoma Endometrial Carcinoma Biological: XmAb®22841 Biological: Pembrolizumab (Keytruda®) Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 242 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Multiple-Dose Study to Evaluate the Safety and Tolerability of XmAb®22841 Monotherapy and in Combination With Pembrolizumab in Subjects With Selected Advanced Solid Tumors (DUET-4)
Actual Study Start Date : May 29, 2019
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : November 2025


Arm Intervention/treatment
Experimental: Arm 1
Arm 1: XmAb®22841 Monotherapy
Biological: XmAb®22841
Monoclonal bispecific antibody

Experimental: Arm 2
Arm 2: Combination of XmAb®22841 and Pembrolizumab (Keytruda®)
Biological: XmAb®22841
Monoclonal bispecific antibody

Biological: Pembrolizumab (Keytruda®)
FDA-approved humanized monoclonal antibody




Primary Outcome Measures :
  1. Safety and tolerability profile of XmAb22841 assessed by rates of treatment-related adverse events (AEs), graded by CTCAE v4.03. [ Time Frame: 56 Days ]
    Rates of treatment-related adverse events (AEs), graded by CTCAE v4.03, and additionally categorized as either immune-related or non-immune AEs.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

PART A (Dose Escalation Cohorts)

  1. All subjects' cancer must have progressed after treatment with all available therapies that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment.
  2. All subjects must have adequate archival tumor, or give consent to a fresh tumor biopsy.
  3. Subjects have an ECOG performance status of 0-1.
  4. Subjects in monotherapy and combination therapy cohorts must have histologically or cytologically confirmed advanced or metastatic solid tumors, including the following:

    1. Melanoma
    2. Cervical carcinoma
    3. Pancreatic carcinoma
    4. Breast carcinoma that is estrogen receptor, progesterone receptor, and Her2 negative (TNBC)
    5. Hepatocellular carcinoma
    6. Urothelial carcinoma
    7. Squamous cell carcinoma of the head and neck (HNSCC)
    8. Nasopharyngeal carcinoma (NPC)
    9. Renal cell carcinoma
    10. Colorectal carcinoma or endometrial carcinoma
    11. Small cell lung carcinoma or NSCLC
    12. Gastric or gastroesophageal junction adenocarcinoma
    13. Prostate adenocarcinoma
    14. Epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
    15. Intrahepatic cholangiocarcinoma
  5. Subjects in the combination cohorts in Part A with XmAb22841 and pembrolizumab may have an advanced solid tumor that either:

    • has progressed after treatment with all available therapies that are known to confer clinical benefit, or is intolerant or has refused standard treatment (as for the XmAb22841 monotherapy cohorts), or
    • is of a tumor type for which pembrolizumab is an approved indication and has not previously been treated with an agent targeting PD1 or PDL1.

PART B (Dose Expansion Cohorts)

XmAb22841 Single Agent Cohort

1. Must have histologically or cytologically confirmed advanced or metastatic solid tumor that has progressed after treatment with all available therapies that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment. Eligible tumor types include the following:

  1. Anti-PD1 refractory melanoma (or any uveal melanoma)
  2. Anti-PD1 refractory NSCLC
  3. Anti-PD1 refractory renal cell carcinoma (with clear cell component)
  4. Anti-PD1 refractory urothelial carcinoma
  5. Head and neck squamous cell carcinoma
  6. Hepatocellular carcinoma
  7. Gastric adenocarcinoma
  8. Cervical carcinoma
  9. Breast carcinoma that is estrogen receptor, progesterone receptor, and HER2 negative (TNBC)
  10. Epithelial ovarian cancer
  11. Nasopharyngeal carcinoma
  12. Squamous cell anal carcinoma
  13. Squamous cell penile carcinoma
  14. Squamous cell vulvar carcinoma

XmAb22841 + Pembrolizumab Cohorts

  1. Anti-PD-1 refractory melanoma (excluding uveal melanoma)
  2. Anti-PD-1 naïve melanoma (excluding uveal melanoma)
  3. Anti-PD-1 refractory NSCLC
  4. Anti-PD1 naïve NSCLC

    a. Must be PD-L1 high (TPS ≥ 50%), with no EGFR or ALK aberrations

  5. Anti-PD1 naïve urothelial carcinoma

    1. Must be PDL1 positive (CPS of ≥ 10), or ineligible for any platinum-containing chemotherapy regardless of PDL1 status; or
    2. Had disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy

Exclusion Criteria:

  1. Prior treatment with an investigational anti-LAG3 therapy.
  2. Treatment with any CTLA4 antibody within 16 weeks of the start of study drug for Cohorts 1M, 2M, 3M, 1P, and 2P; within 8 weeks for Cohorts 4M, 5M, 3P, 4P and 4Pi; and within 3 weeks for Cohorts 6M, 7Mi, 7M, 5P, and 6P.
  3. Systemic antineoplastic therapy, unconjugated antibody therapy within 4 weeks of the first dose of study treatment; or radiotherapy within 2 weeks of the first dose of study treatment; or small molecule kinase inhibitors within 6 elimination half-lives of the first dose of study treatment.
  4. Have received prior therapy with an anti-PD1, anti-PDL1, or anti PDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA4, OX 40, CD137) AND were permanently discontinued from that treatment due to an irAE.
  5. Failure to recover from any irAE from prior cancer therapy to Grade ≤ 1.
  6. Failure to recover from any other toxicity (other than immune-related toxicity) related to previous anticancer treatment to Grade ≤ 2.
  7. Active known or suspected autoimmune disease (except that subjects are permitted to enroll if they have vitiligo; type 1 diabetes mellitus; 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).
  8. Receipt of an organ allograft.
  9. Treatment with antibiotics within 14 days prior to first dose of study drug.
  10. Participants with known HIV.
  11. Participants with known chronic hepatitis B virus (HBV) infection treated for less than 3 months prior to study enrollment and/or with a detectable HBV viral load; or hepatitis C virus (HCV) infection that has been treated for less than 4 weeks prior to study enrollment and/or with a detectable HCV viral load; or active HBV/HCV coinfection.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03849469


Contacts
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Contact: Benjamin Thompson, MD, PhD 619-517-7381 bthompson@xencor.com
Contact: Amber Sarot 858-245-9419 asarot@xencor.com

Locations
Show Show 25 study locations
Sponsors and Collaborators
Xencor, Inc.
ICON Clinical Research
Investigators
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Study Director: Benjamin Thompson, MD, PhD Xencor, Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Xencor, Inc.
ClinicalTrials.gov Identifier: NCT03849469    
Other Study ID Numbers: XmAb22841-01
DUET-4 ( Other Identifier: Xencor, Inc. )
First Posted: February 21, 2019    Key Record Dates
Last Update Posted: August 18, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Xencor, Inc.:
DUET-4
Advanced solid tumors
Metastatic solid tumors
Melanoma
Cervical Cancer
Pancreatic Cancer
Triple Negative Breast Cancer
Hepatocellular/Liver Cancer
Urothelial Cancer
Renal Cell Cancer
Squamous Cell Carcinoma of the Head and Neck
Non-small Cell Lung Cancer
Small Cell Lung Cancer
Gastric Cancer
Gastroesophageal Junction Cancer
Lymphocyte-activation gene 3 (LAG3)
Cytotoxic T-lymphocyte-associated protein 4 (CTLA4)
Prostate Cancer
Nasopharyngeal carcinoma
Epithelial ovarian cancer
Fallopian tube cancer
Primary peritoneal carcinoma
Intrahepatic cholangiocarcinoma
Squamous Cell Anal Carcinoma
Squamous Cell Penile Carcinoma
Squamous Cell Vulvar Carcinoma
Colorectal Carcinoma
Endometrial Carcinoma
Additional relevant MeSH terms:
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Carcinoma
Melanoma
Carcinoma, Squamous Cell
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Triple Negative Breast Neoplasms
Fallopian Tube Neoplasms
Nasopharyngeal Carcinoma
Cholangiocarcinoma
Lung Neoplasms
Squamous Cell Carcinoma of Head and Neck
Colorectal Neoplasms
Endometrial Neoplasms
Carcinoma, Non-Small-Cell Lung
Anus Neoplasms
Pancreatic Neoplasms
Small Cell Lung Carcinoma
Vulvar Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas