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
  • Gastric Adenocarcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Melanoma
  • Nasopharyngeal Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Carcinoma
  • Renal Cell Carcinoma
  • Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Not yet 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
  • Colorectal Carcinoma
  • Endometrial Carcinoma
  • Non-small Cell Lung Carcinoma
  • Small Cell Lung Carcinoma
  • Gastric or Gastroesophageal Junction Adenocarcinoma
  • Advanced or Metastatic Solid Tumors

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.

          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. Colorectal or endometrial carcinoma

              11. Small cell lung carcinoma or NSCLC

              12. Gastric or gastroesophageal junction adenocarcinoma

              13. Subjects in the combination cohorts in Part A with XmAb22841 and pembrolizumab
                  must have histologically or cytologically confirmed advanced solid tumors for
                  which pembrolizumab is an approved indication and that 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 18 weeks of the start of study drug (7 weeks
             for XmAb22841 cohorts ≥ 4).

          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 discontinued from that treatment due to a Grade 3 or higher 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.
      
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:Not yet 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
  • 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
  • Lymphocyte-activation gene 3 (LAG3)
  • Cytotoxic T-lymphocyte-associated protein 4 (CTLA4)

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