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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
132
CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.
CDX-301 will be injected once a day for five days before Cycles 1 and 2.
pembrolizumab will be administered every 3 weeks.
Gemcitabine and Nab-paclitaxel will be administered on Day 1, Day 8 and Day 15 of each 4 week Cycle.
HonorHealth Research Insititute
Scottsdale, Arizona, United States
Northside Hospital, Inc.
Atlanta, Georgia, United States
Georgia Cancer Center at Augusta University
Augusta, Georgia, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists
Omaha, Nebraska, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Gabrail Cancer Center Research LLC
Canton, Ohio, United States
Providence Portland Medical Center
Portland, Oregon, United States
Abramson Cancer Center at the University of Pennsylvania
Philadelphia, Pennsylvania, United States
Rhode Island Hospital (RIH) The Miriam Hospital (TMH)
Providence, Rhode Island, United States
...and 1 more locations
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.
Time frame: From first dose through 30 days after last dose
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).
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Prior to each study treatment, multiple timepoints after each study treatment, and at treatment discontinuation up to approximately 1-3 years
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