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

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ClinicalTrials.gov Identifier: NCT03329950
Recruitment Status : Recruiting
First Posted : November 6, 2017
Last Update Posted : August 23, 2018
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 Solid Tumor 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 found on certain cells to activate the immune system which may promote anti-tumor effects in patients with cancer.

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 solid tumors.

Eligible patients that enroll to the dose-escalation portion of the study will be assigned to one of several 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 105 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 : 145 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 Solid Tumors
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 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 in 4 week cycles until progression or intolerance. 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.

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 v4.0 [ Time Frame: Within 28 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. Histologically confirmed diagnosis of one of the following cancers: melanoma (including mucosal and/or ocular), bladder/urothelial, non-small cell lung cancer, pancreatic adenocarcinoma, breast, colorectal, gastric, esophageal, renal cell, hepatic, ovarian, head and neck, cholangiocarcinoma, fallopian, or primary peritoneal carcinoma. Patients with other tumor types may be permitted to be enrolled.
  2. Receipt of all standard therapies for the tumor type:

    1. Must have had all standard approved and unapproved therapies as deemed appropriate by the treating physician.
    2. Patients are not required to have all approved therapies in a drug class (e.g., patients with kidney cancer do not need all tyrosine kinase inhibitors, patients with melanoma do not need all approved checkpoint blockade inhibitors)
    3. Patients who refuse standard therapy are excluded from the study
  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 6 months following last treatment.
  6. Willingness to undergo a tumor biopsy prior to treatment.
  7. Willingness to undergo a tumor biopsy while on study treatment.

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

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: Monica Fulk, RN    480-323-1350    Monica.Fulk@honorhealth.com   
Principal Investigator: Michael Gordon, MD         
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Melissa Diamond    212-824-8449    Melissa.diamond@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: August 23, 2018
Last Verified: August 2018

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

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Adenocarcinoma
Stomach Neoplasms
Head and Neck Neoplasms
Carcinoma, Renal Cell
Esophageal Neoplasms
Fallopian Tube Neoplasms
Cholangiocarcinoma
Carcinoma, Transitional Cell
Liver Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases