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
2 other identifiers
interventional
132
1 country
11
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Dec 2017
Longer than P75 for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 23, 2017
CompletedFirst Posted
Study publicly available on registry
November 6, 2017
CompletedStudy Start
First participant enrolled
December 1, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 13, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
September 13, 2022
CompletedMarch 28, 2024
March 1, 2024
4.8 years
October 23, 2017
March 27, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (7)
Objective Response Rate
Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years.
Clinical benefit rate
Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years
Duration of Response
First occurrence of a documented objective response to disease progression or death (up to approximately 1-3 years)
Progression-free survival
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 from any cause (up to approximately 1-3 years)
- +2 more secondary outcomes
Study Arms (4)
CDX-1140
EXPERIMENTALPart 1: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, intolerance, or two years of treatment.
CDX-1140 and CDX-301
EXPERIMENTALPart 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.
CDX-1140 and pembrolizumab
EXPERIMENTALPart 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.
CDX-1140 and chemotherapy
EXPERIMENTALPart 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.
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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.
- 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
- 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
- \. Patients must have metastatic pancreatic adenocarcinoma, and have not received previous treatment in a metastatic setting
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Celldex Therapeuticslead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (11)
HonorHealth Research Insititute
Scottsdale, Arizona, 85258, United States
Northside Hospital, Inc.
Atlanta, Georgia, 30342, United States
Georgia Cancer Center at Augusta University
Augusta, Georgia, 30912, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists
Omaha, Nebraska, 68130, United States
Icahn School of Medicine at Mount Sinai
New York, New York, 10029, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Gabrail Cancer Center Research LLC
Canton, Ohio, 44718, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Abramson Cancer Center at the University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Rhode Island Hospital (RIH) The Miriam Hospital (TMH)
Providence, Rhode Island, 02903, United States
Houston Methodist
Houston, Texas, 77030, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 23, 2017
First Posted
November 6, 2017
Study Start
December 1, 2017
Primary Completion
September 13, 2022
Study Completion
September 13, 2022
Last Updated
March 28, 2024
Record last verified: 2024-03