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

A Phase 1 Study of CDX-1140 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.

Study Overview

• Status: Completed
• Conditions: Melanoma; Follicular Lymphoma; Renal Cell Carcinoma; Breast Cancer; Head and Neck Cancer; Gastric Cancer; Colorectal Cancer; Esophageal Cancer; Pancreatic Adenocarcinoma; Ovarian Cancer; Fallopian Tube Cancer; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Lymphoplasmacytic Lymphoma; Non-Hodgkin Lymphoma; Cholangiocarcinoma; Non-small Cell Lung Cancer; Primary Peritoneal Cancer; Hepatic Cancer; Diffuse Large B-cell Lymphoma (DLBCL); Bladder Urothelial Carcinoma; Other Solid Tumors; Small Lymphocytic Leukemia; Waldenstrom's Disease; Indolent B-cell Lymphomas; Mucosa Associated Lymphoid Tissue
• Intervention / Treatment: Drug: CDX-1140; Drug: CDX-301; Drug: Chemotherapy; Drug: pembrolizumab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Insititute
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital, Inc.
    • Augusta, Georgia, United States, 30912
      • Georgia Cancer Center at Augusta University
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Oncology Hematology West, PC dba Nebraska Cancer Specialists
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research LLC
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center at the University of Pennsylvania
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital (RIH) The Miriam Hospital (TMH)
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. 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.
2. 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.
3. 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
4. Willingness to undergo a pre-treatment and on-treatment biopsy, if required.

Additional Inclusion Criteria for Part 1:

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

Additional Inclusion Criteria for Part 3:

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

Additional Inclusion Criteria for Part 4:

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

Key Exclusion Criteria:

1. History of severe hypersensitivity reactions to other monoclonal antibodies.
2. Previous treatment with any anti-CD40 antibody or with FLT3L.
3. Inadequate washout period from prior therapy as defined in the Protocol.
4. Major surgery within 4 weeks prior to study treatment.
5. Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to study treatment.
6. 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.
7. Active, untreated central nervous system metastases.
8. Active autoimmune disease or documented history of autoimmune disease.
9. History of (non-infectious) pneumonitis or has current pneumonitis.
10. Active infection requiring systemic therapy, known infection of HIV, Hepatitis B, or Hepatitis C.

Additional Exclusion Criteria for lymphoma patients in Part 1:

1. Prior allogenic stem cell transplantation
2. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CDX-1140; Part 1: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, intolerance, or two years of treatment.	Drug: CDX-1140; CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.
Experimental: CDX-1140 and CDX-301; Part 2: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, intolerance or two years of treatment. A fixed dose of CDX-301 is injected once a day for five days before cycles 1 and 2 of CDX-1140.	Drug: CDX-1140; CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.; Drug: CDX-301; CDX-301 will be injected once a day for five days before Cycles 1 and 2.
Experimental: CDX-1140 and pembrolizumab; Part 3: Eligible patients will receive CDX-1140, based on cohort assigned, in 3 week cycles until progression, or intolerance, or two years of treatment. A fixed dose of pembrolizumab will also be given in 3 week cycles.	Drug: CDX-1140; CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.; Drug: pembrolizumab; pembrolizumab will be administered every 3 weeks.; Other Names: KEYTRUDA®
Experimental: CDX-1140 and chemotherapy; Part 4: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, or intolerance, or two years of treatment. Chemotherapy will also be given according to standard of care.	Drug: CDX-1140; CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.; Drug: Chemotherapy; Gemcitabine and Nab-paclitaxel will be administered on Day 1, Day 8 and Day 15 of each 4 week Cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of CDX-1140 as assessed by CTCAE v5.0	The rates of drug-related adverse events will be summarized and maximum tolerated dose will be determined.	From first dose through 30 days after last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	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).	Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years.
Clinical benefit rate	The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least four months	Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years
Duration of Response	The interval from which measurement criteria are first met for CR or PR until the first date that progressive disease is objectively documented	First occurrence of a documented objective response to disease progression or death (up to approximately 1-3 years)
Progression-free survival	The time from start of study drug to time of progression or death, whichever occurs first	From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 1-3 years)
Overall survival	The time from start of study drug to death	The time from start of study drug to death from any cause (up to approximately 1-3 years)
Immunogenicity evaluation	Serum samples will be obtained for assessment of human anti-CDX-1140 and anti-CDX-301 antibodies	Prior to each dose of study treatment and at treatment discontinuation, up to approximately 1-3 years
Pharmacokinetic evaluation	CDX-1140 and CDX-301 concentrations will be measured	Prior to each study treatment, multiple timepoints after each study treatment, and at treatment discontinuation up to approximately 1-3 years

Collaborators and Investigators

• Sponsor: Celldex Therapeutics
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2017
• Primary Completion (Actual): September 13, 2022
• Study Completion (Actual): September 13, 2022

Study Registration Dates

• First Submitted: October 23, 2017
• First Submitted That Met QC Criteria: October 31, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Gemcitabine; Lung Cancer; Follicular Lymphoma; Antibody; Chemotherapy; Keytruda; TNBC; Solid Tumors; Non-Hodgkin Lymphoma; Oral cancer; Oropharyngeal cancer; Liver Cancer; pembrolizumab; Kidney Cancer; GI Cancer; Pancreas cancer; Nab-paclitaxel; Celldex; CD40L; CD40; RCC; Laryngeal cancer; Metastatic lung cancer; Bile duct cancer; Monoclonal; CDX-1140; Dendritic cell; CD-40; Flt3l; CDX-301; Keynote A-23; CD40 Ligand; Metastatic pancreas cancer; Unresectable pancreas cancer; Stage IV pancreas cancer; Squamous cell cancer lung; Non-squamous cell cancer lung; Stage IV lung cancer; Squamous cell cancer of head and neck; Stage IV cancer of head and neck; Throat cancer; FLT3 Ligand; fms-like tyrosine kinase 3 ligand; KEYTRUDA®
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lung Diseases; Urogenital Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Adnexal Diseases; Hematologic Diseases; Digestive System Neoplasms; Liver Diseases; Hemorrhagic Disorders; Respiratory Tract Neoplasms; Thoracic Neoplasms; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Fallopian Tube Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lung Neoplasms; Carcinoma; Lymphoma, Non-Hodgkin; Fallopian Tube Neoplasms; Lymphoma, Mantle-Cell; Waldenstrom Macroglobulinemia; Cholangiocarcinoma; Liver Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: CDX1140-01; KEYNOTE-A23 (Other Identifier: Merck)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No