Clinical Trials /

A Study of CDX-1140 as Monotherapy or in Combination in Patients With Advanced Malignancies

NCT03329950

Description:

This is a study to determine the maximum tolerated dose (MTD) for CDX-1140, either alone or in combination with CDX-301 or pembrolizumab, and to further evaluate its tolerability and efficacy in expansion cohorts once the MTD is determined.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Cholangiocarcinoma
  • Colorectal Carcinoma
  • Diffuse Large B-Cell Lymphoma
  • Esophagogastric Carcinoma
  • Fallopian Tube Carcinoma
  • Head and Neck Carcinoma
  • Indolent Non-Hodgkin Lymphoma
  • Liver and Intrahepatic Bile Duct Carcinoma
  • Malignant Solid Tumor
  • Mantle Cell Lymphoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Adenocarcinoma
  • Primary Peritoneal Carcinoma
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of CDX-1140 as Monotherapy or in Combination in Patients With Advanced Malignancies
  • Official Title: A Phase 1 Study of CDX-1140 as Monotherapy or in Combination in Patients With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: CDX1140-01
  • SECONDARY ID: Keynote-A23
  • NCT ID: NCT03329950

Conditions

  • Melanoma
  • Non-small Cell Lung Cancer
  • Breast Cancer
  • Gastric Cancer
  • Renal Cell Carcinoma
  • Ovarian Cancer
  • Cholangiocarcinoma
  • Bladder Urothelial Carcinoma
  • Pancreatic Adenocarcinoma
  • Colorectal Cancer
  • Esophageal Cancer
  • Hepatic Cancer
  • Head and Neck Cancer
  • Primary Peritoneal Cancer
  • Fallopian Tube Cancer
  • Other Solid Tumors
  • Diffuse Large B-cell Lymphoma (DLBCL)
  • Mantle Cell Lymphoma
  • Indolent B-cell Lymphomas
  • Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
CDX-1140CDX-1140
CDX-301CDX-1140 and CDX-301
PembrolizumabCDX-1140 and pembrolizumab

Purpose

This is a study to determine the maximum tolerated dose (MTD) for CDX-1140, either alone or in combination with CDX-301 or pembrolizumab, and to further evaluate its tolerability and efficacy in expansion cohorts once the MTD is determined.

Detailed Description

      This study will determine the MTD of CDX-1140 while also evaluating the safety, tolerability
      and efficacy of CDX-1140 alone (Part 1) or in combination with CDX-301 (Part 2) or
      pembrolizumab (Part 3) in patients with cancer.

      Eligible patients that enroll to the dose-escalation portion of the study will be assigned to
      one of several dose levels of CDX-1140. The dose-escalation part of the study will test the
      safety profile of CDX-1140, alone or in combination with CDX-301 or pembrolizumab, and
      determine which dose(s) of CDX-1140 will be studied in the expansion portions of the study.

      Up to 140 patients will be enrolled for CDX-1140 monotherapy, up to 40 patients will be
      enrolled for CDX-1140 in combination with CDX-301, and up to 40 patients will be enrolled for
      CDX-1140 in combination with pembrolizumab.

      All patients enrolled in the study will be closely monitored to determine if there is a
      response to the treatment as well as for any side effects that may occur.
    

Trial Arms

NameTypeDescriptionInterventions
CDX-1140ExperimentalPart 1: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, intolerance, or two years of treatment.
  • CDX-1140
CDX-1140 and CDX-301ExperimentalPart 2: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, intolerance or two years of treatment. A fixed dose of CDX-301 is injected once a day for five days before cycles 1 and 2 of CDX-1140.
  • CDX-1140
  • CDX-301
CDX-1140 and pembrolizumabExperimentalPart 3: Eligible patients will receive CDX-1140, based on cohort assigned, in 3 week cycles until progression, or intolerance, or two years of treatment. A fixed dose of pembrolizumab will also be given in 3 week cycles.
  • CDX-1140
  • Pembrolizumab

Eligibility Criteria

        Key Inclusion Criteria:

          1. Recurrent, locally advanced or metastatic melanoma (including mucosal and/or ocular),
             bladder/urothelial, non-small cell lung cancer, pancreatic adenocarcinoma, breast,
             colorectal, gastric, esophageal, renal cell, hepatic, ovarian fallopian or primary
             peritoneal carcinoma, head and neck, and cholangiocarcinoma. Additional tumor types
             (except primary CNS tumors) may be enrolled after discussion with, and approval from,
             the medical monitor.

          2. Must have received all standard of care therapies (approved or unapproved) as deemed
             appropriate by the treating physician. Patients who refuse standard therapy are
             excluded from the study.

          3. If of childbearing potential (male or female), agrees to practice an effective form of
             contraception during study treatment and for at least 3 months following last
             treatment

          4. Willingness to undergo a pre-treatment and on-treatment biopsy, if required.

        Additional Inclusion Criteria for Part 1:

          1. Advanced diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, or indolent
             B-cell lymphoma are also eligible.

          2. Lymphoma patients must have received ≥ 1 prior systemic therapy

        Additional Inclusion Criteria for Part 3:

          1. Patients must have documented progression while receiving anti-PD-1 or anti-PD-L1
             based regimens for FDA approved indications

          2. Patients cannot have received more than one anti-PD-1 or anti-PD-L1 based regimen

        Key Exclusion Criteria:

          1. History of severe hypersensitivity reactions to other monoclonal antibodies.

          2. Previous treatment with any anti-CD40 antibody or with FLT3L.

          3. Inadequate washout period from prior therapy as defined in the Protocol.

          4. Major surgery within 4 weeks prior to study treatment.

          5. Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within
             2 weeks prior to study treatment.

          6. Other prior malignancy, except for adequately treated basal or squamous cell skin
             cancer or in situ cancers. For all other cancers, the patient must be disease-free for
             at least 3 years to be allowed to enroll.

          7. Active, untreated central nervous system metastases.

          8. Active autoimmune disease or documented history of autoimmune disease.

          9. History of (non-infectious) pneumonitis or has current pneumonitis.

         10. Active infection requiring systemic therapy, known infection of HIV, Hepatitis B, or
             Hepatitis C.

        Additional Exclusion Criteria for lymphoma patients in Part 1:

          1. Prior allogenic stem cell transplantation

          2. Patients who have received autologous stem cell transplant ≤ 12 weeks prior to the
             first dose of study drug.

        There are additional criteria your study doctor will review with you to confirm your
        eligibility for the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and Tolerability of CDX-1140 as assessed by CTCAE v5.0
Time Frame:From first dose through 30 days after last dose
Safety Issue:
Description:The rates of drug-related adverse events will be summarized and maximum tolerated dose will be determined.

Secondary Outcome Measures

Measure:Objective Response Rate
Time Frame:Every 9-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years.
Safety Issue:
Description:The percentage of patients who achieved a confirmed complete response or partial response by evaluation criteria in solid tumors for immune-based therapeutics (iRECIST; for solid tumor patients) and the lymphoma response to immunomodulatory therapy criteria (LYRIC; for lymphoma patients).
Measure:Clinical benefit rate
Time Frame:Every 9-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years
Safety Issue:
Description:The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least four months
Measure:Duration of Response
Time Frame:First occurrence of a documented objective response to disease progression or death (up to approximately 1-3 years)
Safety Issue:
Description:The interval from which measurement criteria are first met for CR or PR until the first date that progressive disease is objectively documented
Measure:Progression-free survival
Time Frame:From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 1-3 years)
Safety Issue:
Description:The time from start of study drug to time of progression or death, whichever occurs first
Measure:Overall survival
Time Frame:The time from start of study drug to death from any cause (up to approximately 1-3 years)
Safety Issue:
Description:The time from start of study drug to death
Measure:Immunogenicity evaluation
Time Frame:Prior to each dose of study treatment and at treatment discontinuation, up to approximately 1-3 years
Safety Issue:
Description:Serum samples will be obtained for assessment of human anti-CDX-1140 and anti-CDX-301 antibodies
Measure:Pharmacokinetics
Time Frame:Pre-dose, 45 minutes and 90 minutes, and then at 1, 2, 4, 6 and 24 hours following the first two doses, prior to each additional dose of study treatment and at treatment discontinuation, up to approximately 1-3 years
Safety Issue:
Description:CDX-1140 and CDX-301 concentrations will be measured

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Celldex Therapeutics

Trial Keywords

  • CDX-1140
  • Solid Tumors
  • Liver Cancer
  • GI Cancer
  • Kidney Cancer
  • Celldex
  • Monoclonal
  • Antibody
  • CD40
  • CD-40
  • Flt3l
  • CDX-301
  • Lung Cancer
  • Bile duct cancer
  • TNBC
  • RCC
  • Non-Hodgkin Lymphoma
  • Follicular Lymphoma
  • Dendritic cell
  • Keynote A-23
  • pembrolizumab
  • Keytruda

Last Updated

April 10, 2020