Clinical Trials /

A Study of XmAb®22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors

NCT03849469

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Cervical Carcinoma
  • Colorectal Carcinoma
  • Endometrial Carcinoma
  • Fallopian Tube Carcinoma
  • Gastric Adenocarcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Intrahepatic Cholangiocarcinoma
  • Malignant Solid Tumor
  • Melanoma
  • Nasopharyngeal Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Primary Peritoneal Carcinoma
  • Prostate Adenocarcinoma
  • Renal Cell Carcinoma
  • Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of XmAb®22841 Monotherapy & in Combination w/ Pembrolizumab in Subjects w/ Selected Advanced Solid Tumors
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: XmAb22841-01
  • SECONDARY ID: DUET-4
  • NCT ID: NCT03849469

Conditions

  • 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
  • MSI-H
  • Mismatch Repair Deficiency
  • Epithelial Ovarian Cancer
  • Fallopian Tube Cancer
  • Primary Peritoneal Carcinoma
  • Intrahepatic Cholangiocarcinoma

Interventions

DrugSynonymsArms
XmAb®22841Arm 1
Pembrolizumab (Keytruda®)Arm 2

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm 1ExperimentalArm 1: XmAb®22841 Monotherapy
  • XmAb®22841
Arm 2ExperimentalArm 2: Combination of XmAb®22841 and Pembrolizumab (Keytruda®)
  • XmAb®22841
  • Pembrolizumab (Keytruda®)

Eligibility Criteria

        Inclusion Criteria:

          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 (excluding uveal 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. Microsatellite instability-high or mismatch repair deficient tumors

              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

              16. 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.

        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, and 4P; and
             within 3 weeks for Cohorts 6M, 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Details

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

Trial Keywords

  • 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
  • MSI (microsatellite instability)-high tumors
  • MMR (mismatch repair)-deficient tumors
  • Nasopharyngeal carcinoma
  • Epithelial ovarian cancer
  • Fallopian tube cancer
  • Primary peritoneal carcinoma
  • Intrahepatic cholangiocarcinoma

Last Updated

December 12, 2019