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

Study Description

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 Design

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Arms and Interventions

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Outcome Measures

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Eligibility Criteria

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Contacts and Locations

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

More Information

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Celldex Therapeutics
ClinicalTrials.gov Identifier:	NCT03329950 History of Changes
Other Study ID Numbers:	CDX1140-01
First Posted:	November 6, 2017
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