A Study of CDX-1140 as Monotherapy or in Combination in Patients With Advanced Malignancies
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| ClinicalTrials.gov Identifier: NCT03329950 |
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Recruitment Status :
Recruiting
First Posted : November 6, 2017
Last Update Posted : August 6, 2019
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| 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 |
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 |
|---|---|
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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. |
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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. |
- 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.
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.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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
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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
- Measurable disease.
- Life expectancy ≥ 12 weeks.
- 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.
- Willingness to undergo a pre-treatment and on-treatment biopsy, if required.
Exclusion Criteria:
- History of severe hypersensitivity reactions to other monoclonal antibodies.
- Previous treatment with any anti-CD40 antibody or with FLT3L.
- 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.
- Prior T-cell or other cell-based therapies within 12 weeks (or 2 weeks if patient experienced disease progression on the prior treatment)
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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.
- Chemotherapy within 21 days (6 weeks for nitrosoureas) or at least 5 half-lives (whichever is longer) prior to study treatment.
- Received any kinase inhibitors within 2 weeks prior to study treatment.
- Systemic radiation therapy within 4 weeks, prior focal radiotherapy within 2 weeks, or radiopharmaceuticals (strontium, samarium) within 8 weeks prior to study treatment.
- Major surgery within 4 weeks prior to study treatment.
- Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to study treatment.
- 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.
- Active, untreated central nervous system metastases.
- Active autoimmune disease or documented history of autoimmune disease.
- Active infection requiring systemic therapy, known infection of HIV, Hepatitis B, or Hepatitis C.
- 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.
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
| Contact: Celldex Therapeutics | 844-723-9363 | info@celldex.com |
| 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: 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 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 | |
| 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 6, 2019 |
| Last Verified: | February 2019 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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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 |
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Lymphoma Carcinoma Lymphoma, Non-Hodgkin Lymphoma, B-Cell Lymphoma, Mantle-Cell Carcinoma, Renal Cell Lymphoma, Large B-Cell, Diffuse Fallopian Tube Neoplasms Cholangiocarcinoma Liver Neoplasms Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders |
Immune System Diseases Neoplasms, Glandular and Epithelial Neoplasms by Site Digestive System Neoplasms Digestive System Diseases Adenocarcinoma Adnexal Diseases Genital Diseases, Female Genital Neoplasms, Female Urogenital Neoplasms Kidney Neoplasms Urologic Neoplasms Kidney Diseases Urologic Diseases Fallopian Tube Diseases |