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

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ClinicalTrials.gov Identifier: NCT03329950
Recruitment Status : Recruiting
First Posted : November 6, 2017
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Celldex Therapeutics

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

Condition or disease Intervention/treatment Phase
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 Drug: CDX-1140 Drug: CDX-301 Phase 1

Detailed Description:

CDX-1140 is a fully human monoclonal antibody that binds to a cell receptor called CD40 expressed on certain cells and which activates the immune system, which then may promote anti-tumor effects in patients with cancer. CD40 is also expressed on some types of cancer cells and CDX-1140 may directly cause those cells to die.

CDX-301 is a growth factor for dendritic cells, a key cell type that regulates immune responses, including anti-tumor immune responses.

This study will determine the MTD of CDX-1140 while also evaluating the safety, tolerability and efficacy of CDX-1140 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, 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.

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of CDX-1140 as Monotherapy or in Combination in Patients With Advanced Malignancies
Actual Study Start Date : December 1, 2017
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: CDX-1140

Part 1: Dose-escalation phase: Eligible patients will receive CDX-1140 treatments, based on cohort assigned, in 4 week cycles until progression or intolerance.

Expansion phase: To further study the safety, tolerability, and efficacy of CDX-1140. Patients enrolled in the expansion phase of the study will receive CDX-1140 at the dose level(s) chosen during the escalation phase.

Drug: CDX-1140
CDX-1140 will be administered every 4 weeks.

Experimental: CDX-1140 and CDX-301

Part 2: Dose-escalation phase: Eligible patients will receive CDX-1140 treatments, based on cohort assigned, in 4 week cycles until progression or intolerance. A fixed dose of CDX-301 is injected once a day for five days before cycles 1 and 2 of CDX-1140.

Expansion Phase: To further study the safety, tolerability, and efficacy of CDX-1140 and CDX-301. Patients enrolled in the expansion phase of Part 2 will receive CDX-1140 at the dose level(s) chosen during the escalation phase and the fixed dose of CDX-301 from the Dose-escalation phase.

Drug: CDX-1140
CDX-1140 will be administered every 4 weeks.

Drug: CDX-301
CDX-301 will be injected once a day for five days before Cycles 1 and 2.




Primary Outcome Measures :
  1. Safety and Tolerability of CDX-1140 as assessed by CTCAE v5.0 [ Time Frame: Within 35 days after first dose ]
    The rates of drug-related adverse events, serious drug-related adverse events, dose-limiting toxicities, laboratory test abnormalities, and maximum tolerated dose will be determined.



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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:

  1. Diagnosed with one of the following:

    • 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.
    • Advanced diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, or indolent B-cell lymphoma
  2. Criteria A and B:

    A. For patients with solid tumors:

    • Must have received all standard of care therapies (approved or unapproved) as deemed appropriate by the treating physician
    • Patients are not required to have all approved therapies in a particular class of drugs (e.g. all approved tyrosine kinase inhibitors for patients with renal cell carcinoma or all approved checkpoint blockade antibodies for patients with melanoma)
    • Patients who refuse standard therapy are excluded from the study

    B. For patients with lymphoma: Must have received ≥ 1 prior systemic therapy

  3. Measurable disease.
  4. Life expectancy ≥ 12 weeks.
  5. 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.
  6. Willingness to undergo a pre-treatment and on-treatment biopsy, if required.

Exclusion Criteria:

  1. History of severe hypersensitivity reactions to other monoclonal antibodies.
  2. Previous treatment with any anti-CD40 antibody or with FLT3L.
  3. Received any antibody targeting T-cell check point or co-stimulation pathways within 4 weeks, received any other monoclonal antibody within 4 weeks, and all other immunotherapy (tumor vaccine, cytokine, or growth factor) within 2 weeks prior to study treatment.
  4. Prior T-cell or other cell-based therapies within 12 weeks (or 2 weeks if patient experienced disease progression on the prior treatment)
  5. For lymphoma patients:

    • Prior allogenic stem cell transplantation
    • Patients who have received autologous stem cell transplant ≤ 12 weeks prior to the first dose of study drug.
  6. Chemotherapy within 21 days (6 weeks for nitrosoureas) or at least 5 half-lives (whichever is longer) prior to study treatment.
  7. Received any kinase inhibitors within 2 weeks prior to study treatment.
  8. Systemic radiation therapy within 4 weeks, prior focal radiotherapy within 2 weeks, or radiopharmaceuticals (strontium, samarium) within 8 weeks prior to study treatment.
  9. Major surgery within 4 weeks prior to study treatment.
  10. Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to study treatment.
  11. 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.
  12. Active, untreated central nervous system metastases.
  13. Active autoimmune disease or documented history of autoimmune disease.
  14. Active infection requiring systemic therapy, known infection of HIV, Hepatitis B, or Hepatitis C.
  15. Significant cardiovascular disease including Congestive Heart Failure or poorly controlled hypertension.

There are additional criteria your study doctor will review with you to confirm your eligibility for the study.


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): NCT03329950


Contacts
Contact: Celldex Therapeutics 844-723-9363 info@celldex.com

Locations
United States, Arizona
HonorHealth Research Insititute Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Michael Gordon, MD    480-323-1350    Michael.Gordon@honorhealth.com   
Contact: Melodi Priddy    480-323-1346    Melodi.priddy@honorhealth.com   
Principal Investigator: Michael Gordon, MD         
United States, Georgia
Northside Hospital, Inc. Recruiting
Atlanta, Georgia, United States, 30342
Contact: Rodolfo Bordoni, MD    404-303-3355    clinicaltrials@northside.com   
Principal Investigator: Rodolfo Bordoni, MD         
United States, Nebraska
Oncology Hematology West, PC dba Nebraska Cancer Specialists Recruiting
Omaha, Nebraska, United States, 68130
Contact: Megan Meays    402-691-6971    mmeays@nebraskacancer.com   
Contact: Gladys Pierce    402-691-6972    gpierce@nebraskacancer.com   
Principal Investigator: Ralph Hauke, MD         
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Tiara Hills    212-824-8449    tiara.hills@mssm.edu   
Principal Investigator: Nina Bhardwaj, MD         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Danny Khalil, MD    646-888-4384    khalild@mskcc.org   
Principal Investigator: Danny Khalil, MD         
United States, Ohio
Gabrail Cancer Center Research LLC Recruiting
Canton, Ohio, United States, 44718
Contact: Carrie Smith    330-492-3345 ext 208    csmith@gabrailcancercenter.com   
Contact: Brittany Dunn    330-492-3345 ext 213    bdunn@gabrailcancercenter.com   
Principal Investigator: Nashat Gabrail, MD         
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Brenda Fisher, RN    503-215-2613    Brenda.Fisher@providence.org   
Contact: Tara Foote, RN    503-215-7192    Tara.Foote@providence.org   
Principal Investigator: Rachel Sanborn, MD         
United States, Pennsylvania
Abramson Cancer Center at the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Sagan Loburak    215-614-7677    Sagan.Loburak@uphs.upenn.edu   
Contact: Jennifer Louie    215-220-9668    Jennifer.Louie2@uphs.upenn.edu   
Principal Investigator: Mark O'Hara, MD         
Sponsors and Collaborators
Celldex Therapeutics

Responsible Party: Celldex Therapeutics
ClinicalTrials.gov Identifier: NCT03329950     History of Changes
Other Study ID Numbers: CDX1140-01
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: February 2019

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Celldex Therapeutics:
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

Additional relevant MeSH terms:
Lymphoma
Carcinoma
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Adenocarcinoma
Lymphoma, Non-Hodgkin
Stomach Neoplasms
Lymphoma, B-Cell
Head and Neck Neoplasms
Lymphoma, Mantle-Cell
Carcinoma, Renal Cell
Esophageal Neoplasms
Lymphoma, Large B-Cell, Diffuse
Fallopian Tube Neoplasms
Cholangiocarcinoma
Carcinoma, Transitional Cell
Liver Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Glandular and Epithelial
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site