Clinical trial NCT03329950: A Study of CDX-1140 (CD40) as Monotherapy or in Combination in Patients With Advanced Malignancies
Official title: A Phase 1 Study of CDX-1140 as Monotherapy or in Combination in Patients With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Follicular Lymphoma
Lymphoplasmacytic Lymphoma
Waldenstrom's Disease
Marginal Zone Lymphoma
Mucosa Associated Lymphoid Tissue
Small Lymphocytic Leukemia
Keywords: 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
Keynote A-23
pembrolizumab
Keytruda
Chemotherapy
Gemcitabine
Nab-paclitaxel
CD40L
CD40 Ligand
Pancreas cancer
Metastatic pancreas cancer
Unresectable pancreas cancer
Stage IV pancreas cancer
Squamous cell cancer lung
Non-squamous cell cancer lung
Metastatic lung cancer
Stage IV lung cancer
Squamous cell cancer of head and neck
Stage IV cancer of head and neck
Throat cancer
Oropharyngeal cancer
Laryngeal cancer
Oral cancer
FLT3 Ligand
fms-like tyrosine kinase 3 ligand
KEYTRUDA®
Lead sponsor: Celldex Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-11-06
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and Tolerability of CDX-1140 as assessed by CTCAE v5.0
timeFrame: From first dose through 30 days after last dose
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years.
measure: Clinical benefit rate
timeFrame: Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years
measure: Duration of Response
timeFrame: First occurrence of a documented objective response to disease progression or death (up to approximately 1-3 years)
measure: Progression-free survival
timeFrame: From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 1-3 years)
measure: Overall survival
timeFrame: The time from start of study drug to death from any cause (up to approximately 1-3 years)
measure: Immunogenicity evaluation
timeFrame: Prior to each dose of study treatment and at treatment discontinuation, up to approximately 1-3 years
measure: Pharmacokinetic evaluation
timeFrame: Prior to each study treatment, multiple timepoints after each study treatment, and at treatment discontinuation up to approximately 1-3 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Insititute
state: Arizona
city: Atlanta
country: United States
facility: Northside Hospital, Inc.
state: Georgia
city: Augusta
country: United States
facility: Georgia Cancer Center at Augusta University
state: Georgia
city: Omaha
country: United States
facility: Oncology Hematology West, PC dba Nebraska Cancer Specialists
state: Nebraska
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Canton
country: United States
facility: Gabrail Cancer Center Research LLC
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: Abramson Cancer Center at the University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital (RIH) The Miriam Hospital (TMH)
state: Rhode Island
city: Houston
country: United States
facility: Houston Methodist
state: Texas
Study officials:
References: