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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03329950
Recruitment Status : Recruiting
First Posted : November 6, 2017
Last Update Posted : August 27, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Celldex Therapeutics

Study Description
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Brief Summary:
This is a study to determine the maximum tolerated dose (MTD) for CDX-1140 (CD40 antibody), either alone or in combination with CDX-301 (FLT3L), pembrolizumab, or chemotherapy 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 Follicular Lymphoma Lymphoplasmacytic Lymphoma Waldenstrom's Disease Marginal Zone Lymphoma Mucosa Associated Lymphoid Tissue Small Lymphocytic Leukemia Drug: CDX-1140 Drug: CDX-301 Drug: Pembrolizumab Drug: Chemotherapy Phase 1

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), pembrolizumab (Part 3), or chemotherapy (Part 4) 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, pembrolizumab or chemotherapy and determine which dose(s) of CDX-1140 will be studied in the expansion portions of the study.

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 260 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 : August 2021
Estimated Study Completion Date : November 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: CDX-1140
Part 1: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, intolerance, or two years of treatment.
 Drug: CDX-1140
CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.
Experimental: CDX-1140 and CDX-301
Part 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.
 Drug: CDX-1140
CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.

Drug: CDX-301
CDX-301 will be injected once a day for five days before Cycles 1 and 2.
Experimental: CDX-1140 and pembrolizumab
Part 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.
 Drug: CDX-1140
CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.

Drug: Pembrolizumab
Pembrolizumab will be administered every 3 weeks.
Experimental: CDX-1140 and chemotherapy
Part 4: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, or intolerance, or two years of treatment. Chemotherapy will also be given according to standard of care.
 Drug: CDX-1140
CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.

Drug: Chemotherapy
Gemcitabine and Nab-paclitaxel will be administered on Day 1, Day 8 and Day 15 of each 4 week Cycle.


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


Secondary Outcome Measures :
  1. Objective Response Rate [ Time Frame: Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years. ]
    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).

  2. Clinical benefit rate [ Time Frame: Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years ]
    The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least four months

  3. Duration of Response [ Time Frame: First occurrence of a documented objective response to disease progression or death (up to approximately 1-3 years) ]
    The interval from which measurement criteria are first met for CR or PR until the first date that progressive disease is objectively documented

  4. 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) ]
    The time from start of study drug to time of progression or death, whichever occurs first

  5. Overall survival [ Time Frame: The time from start of study drug to death from any cause (up to approximately 1-3 years) ]
    The time from start of study drug to death

  6. Immunogenicity evaluation [ Time Frame: Prior to each dose of study treatment and at treatment discontinuation, up to approximately 1-3 years ]
    Serum samples will be obtained for assessment of human anti-CDX-1140 and anti-CDX-301 antibodies

  7. Pharmacokinetic evaluation [ Time Frame: Prior to each study treatment, multiple timepoints after each study treatment, and at treatment discontinuation up to approximately 1-3 years ]
    CDX-1140 and CDX-301 concentrations will be measured


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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

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

Additional Inclusion Criteria for Part 4:

1. Patients must have metastatic pancreatic adenocarcinoma, and have not received previous treatment in a metastatic setting

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.

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

Locations
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United States, Arizona
HonorHealth Research Insititute Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Michael Gordon, MD    480-323-1350    Michael.Gordon@honorhealth.com   
Contact: Dan Mocan    480-323-3661    dmocan@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         
Georgia Cancer Center at Augusta University Recruiting
Augusta, Georgia, United States, 30912
Contact: Kelly Jenkins    706-721-1206    kjenkins@augusta.edu   
Contact: Patricia Loveday    706-721-5095    ploveday@augusta.edu   
Principal Investigator: Vamsi Kota, 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: Daniela Delbeau, MSN, AGCNS-BC, RN    212-824-7811    Daniela.Delbeau@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 Dessecker    330-492-3345 ext 213    bdessecker@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         
United States, Rhode Island
Rhode Island Hospital (RIH) The Miriam Hospital (TMH) Recruiting
Providence, Rhode Island, United States, 02903
Contact: Rachel Kuhlman, MBA, BS, BA    401-444-5014    RKuhlman@lifespan.org   
Principal Investigator: Adam Olszewski, MD         
United States, Texas
Houston Methodist Recruiting
Houston, Texas, United States, 77030
Contact: Michael Shephard, MD       mailto:mshephard@houstonmethodist.org   
Principal Investigator: Maen Abdelrahim, MD         
Sponsors and Collaborators
Celldex Therapeutics
Merck Sharp & Dohme Corp.
More Information
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Responsible Party: Celldex Therapeutics
ClinicalTrials.gov Identifier: NCT03329950    
Other Study ID Numbers: CDX1140-01
Keynote-A23 ( Other Identifier: Merck )
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: August 27, 2020
Last Verified: August 2020

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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 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
Keynote A-23
pembrolizumab
Keytruda
Chemotherapy
Gemcitabine
Nab-paclitaxel
CD40L
CD40 Ligand
Pancreas cancer
Metastatic pancreas cancer
Unresectable pancreas cancer
Additional relevant MeSH terms:
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Lymphoma
Carcinoma
Lung Neoplasms
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Fallopian Tube Neoplasms
Cholangiocarcinoma
Waldenstrom Macroglobulinemia
Liver Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
 Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Glandular and Epithelial
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Digestive System Neoplasms
Digestive System Diseases
Adenocarcinoma
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms