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

Status: Active

Description

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.

Eligibility Criteria

Inclusion Criteria

  • 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
  • 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)
  • 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.

Locations & Contacts

New York

New York
Icahn School of Medicine at Mount Sinai
Status: Active
Contact: Melissa Diamond
Phone: 212-824-8449
Email: melissa.diamond@mssm.edu
Memorial Sloan Kettering Cancer Center
Status: Active
Name Not Available

Ohio

Columbus
Ohio State University Comprehensive Cancer Center
Status: In review
Name Not Available

Pennsylvania

Philadelphia
University of Pennsylvania / Abramson Cancer Center
Status: Active
Name Not Available

Trial Objectives and Outline

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.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Celldex Therapeutics Inc

Trial IDs

Primary ID CDX1140-01
Secondary IDs NCI-2018-00959
Clinicaltrials.gov ID NCT03329950