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NCT Number: NCT03329950

A Study of CDX-1140 (CD40) as Monotherapy or in Combination in Patients With Advanced Malignancies

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.

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Key information

Conditions

Melanoma Adenocarcinoma Adnexal Diseases Bile Duct Diseases Bile Duct Neoplasms Biliary Tract Diseases Biliary Tract Neoplasms Bladder Urothelial Carcinoma Blood Protein Disorders Breast Cancer Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Carcinoma, Renal Cell Cholangiocarcinoma Colonic Diseases Colorectal Cancer Colorectal Neoplasms Congenital, Hereditary, and Neonatal Diseases and Abnormalities Diffuse Large B-Cell Lymphoma (DLBCL) Digestive System Diseases Digestive System Neoplasms Dysgammaglobulinemia Endocrine Gland Neoplasms Endocrine System Diseases Esophageal Cancer Esophageal Diseases Esophageal Neoplasms Fallopian Tube Cancer Fallopian Tube Diseases Fallopian Tube Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Follicular Lymphoma Gastric Cancer Gastrointestinal Diseases Gastrointestinal Neoplasms Genetic Diseases, Inborn Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Head and Neck Cancer Head and Neck Neoplasms Hematologic Diseases Hemic and Lymphatic Diseases Hepatic Cancer Hyper-IgM Immunodeficiency Syndrome Immune System Diseases Immunologic Deficiency Syndromes Immunoproliferative Disorders Indolent B-cell Lymphomas Intestinal Diseases Intestinal Neoplasms Kidney Diseases Kidney Neoplasms Laryngeal Diseases Laryngeal Neoplasms Liver Diseases Liver Neoplasms Lung Diseases Lung Neoplasms Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, B-Cell, Marginal Zone Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Lymphoplasmacytic Lymphoma Lymphoproliferative Disorders Male Urogenital Diseases Mantle Cell Lymphoma Marginal Zone Lymphoma Mouth Diseases Mouth Neoplasms Mucosa Associated Lymphoid Tissue Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Non-Hodgkin Lymphoma Non-small Cell Lung Cancer Oropharyngeal Neoplasms Other Solid Tumors Otorhinolaryngologic Diseases Otorhinolaryngologic Neoplasms Ovarian Cancer Ovarian Diseases Ovarian Neoplasms Pancreatic Adenocarcinoma Pancreatic Diseases Pancreatic Neoplasms Pharyngeal Diseases Pharyngeal Neoplasms Primary Immunodeficiency Diseases Primary Peritoneal Cancer Rectal Diseases Renal Cell Carcinoma Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Small Lymphocytic Leukemia Stomach Diseases Stomach Neoplasms Stomatognathic Diseases Thoracic Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Waldenstrom's Disease

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

HonorHealth Research Insititute, Scottsdale, Arizona, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • 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.
  • 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.
  • 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.

Additional Inclusion Criteria for Part 1:

  • Advanced diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, or indolent B-cell lymphoma are also eligible.
  • Lymphoma patients must have received ≥ 1 prior systemic therapy

Additional Inclusion Criteria for Part 3:

  • Patients must have documented progression while receiving anti-PD-1 or anti-PD-L1 based regimens for FDA approved indications
  • Patients cannot have received more than one anti-PD-1 or anti-PD-L1 based regimen

Additional Inclusion Criteria for Part 4:

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

Key Exclusion Criteria:

  • History of severe hypersensitivity reactions to other monoclonal antibodies.
  • Previous treatment with any anti-CD40 antibody or with FLT3L.
  • Inadequate washout period from prior therapy as defined in the Protocol.
  • 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.
  • History of (non-infectious) pneumonitis or has current pneumonitis.
  • Active infection requiring systemic therapy, known infection of HIV, Hepatitis B, or Hepatitis C.

Additional Exclusion Criteria for lymphoma patients in Part 1:

  • Prior allogenic stem cell transplantation
  • 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.

Treatment and study plan

CDX-1140

Drug

CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.

CDX-301

Drug

CDX-301 will be injected once a day for five days before Cycles 1 and 2.

Pembrolizumab

Drug

pembrolizumab will be administered every 3 weeks.

Other names: KEYTRUDA®

Chemotherapy

Drug

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

Primary outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

Celldex Therapeutics

Industry

Collaborators

  • Merck Sharp & Dohme LLC

Registry information

Official study title

A Phase 1 Study of CDX-1140 as Monotherapy or in Combination in Patients With Advanced Malignancies

Important dates

Study start
2017
Primary completion
2022
Study completion
2022
First posted
Nov 6, 2017
Registry last updated
Mar 28, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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