A Study of CDX-1140, a CD40 Agonist, in Combination With Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects With Biliary Tract Carcinoma (BTC)
A Phase I/II Study of CDX-1140, a CD40 Agonist, in Combination With Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects With Biliary Tract Carcinoma (BTC)
2 other identifiers
interventional
60
1 country
1
Brief Summary
Background: Biliary tract carcinoma (BTC) is cancer of the slender tubes that carry fluids in the liver. People with advanced BTC have few treatment options, and their survival rates are very low. Objective: To test a study drug (CDX-1140) combined 3 other drugs (capecitabine, oxaliplatin, Keytruda) in people with BTC. Eligibility: Adults aged 18 years or older with BTC that progressed after treatment and is not eligible for surgery or liver transplant. Design: Participants will be screened. They will have a physical exam. They will have blood tests and tests of their heart function. They will have imaging scans. They may need to have a biopsy: A small sample of tissue will be taken from their tumor using a small needle. Three of the drugs are given through a tube attached to a needle inserted into a vein in the arm (intravenous). The fourth drug is a pill taken by mouth with water. Participants will be treated in 21-day cycles. They will receive intravenous treatments on day 1 and day 8 of the first 6 cycles. After that, they will receive intravenous treatments only on day 1 of each cycle. Participants will take the pill twice a day only for the first 2 weeks of each cycle. They will stop taking this drug after 6 cycles. Imaging scans will be repeated every 9 weeks. Participants may continue receiving the study treatment for up to 2 years. Follow-up visits, including imaging scans, will continue for 3 more years. These images may be taken at other locations and sent to the researchers.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2024
Longer than P75 for phase_1
1 active site
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
May 8, 2023
CompletedFirst Posted
Study publicly available on registry
May 9, 2023
CompletedStudy Start
First participant enrolled
May 8, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2040
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2042
March 24, 2026
January 22, 2026
16.1 years
May 8, 2023
March 21, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Phase I: Safe dose of CDX-1140 in combination with CAPOX and Keytruda(R)
Estimation of safe dose will be determined based on number of dose limiting toxicities (DLTs) experienced.
35 days
Phase II: 6-month progression free survival (PFS) probability
6-month PFS probability will be calculated using the Kaplan-Meier method.
Study start - 6 months after start of study drug
Phase II: Overall response rate (ORR)
The fraction of participants who experience a response (PR + CR) evaluated every 9 (+/- 4) weeks. Results will be reported along with 80% and 95% two-sided confidence intervals.
Study start until disease progression or 5 years after initiation of study therapy, whichever occurs first.
Secondary Outcomes (2)
Safety of CDX-1140, CAPOX and Keytruda(R) in participants with advanced BTC as determined by toxicities experienced
Day 1 of Cycle 1 through 90 days after the study agents were last administered
5-year overall survival
Study start - 5 years
Study Arms (2)
Phase I
EXPERIMENTALKeytruda, oxaliplatin, capecitabine and escalating doses of CDX-1140
Phase II
EXPERIMENTALKeytruda, oxaliplatin, capecitabine and estimated safe dose of CDX-1140
Interventions
Oxaliplatin (130 mg/m2) will be administered IV on Day 1 of each cycle, every 21 days (up to 6 cycles).
Capecitabine (750 mg/m2 every 12 hours) will be administered orally with an intermittent schedule: 2 weeks on, 1 week off, of each cycle, every 21 days (up to 6 cycles).
Pembrolizumab (200 mg) will be given IV on Day 8 of each cycle every 21 days (up to 6 cycles).
CDX-1140 (0.36-1.5 mg/kg; per assigned dose level) will be given IV on Day 8 of each cycle every 21 days (up to 6 cycles).
Eligibility Criteria
You may qualify if:
- Participants must have histopathological confirmation of BTC or histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of BTC.
- The maximum tumor size of any individual tumor or metastasis must be \<= 8 cm.
- Participants should have progressed on standard of care first line systemic treatment or refused standard treatment.
- Participants must have a disease that is not amenable to potentially curative resection or liver transplantation.
- Participants must have evaluable or measurable disease per RECIST 1.1
- ECOG performance status of 0 to 1
- Participants must have adequate organ and marrow function as defined below:
- Absolute neutrophil count
- (ANC) \>= 1,000/mcL
- Platelets \>= 100,000/mcL
- Total bilirubin \<= 2.5 x ULN
- ALT and AST \<= 5 x ULN.
- Creatinine OR Measured or calculated creatinine clearance (CrCl) (estimated glomerular filtration rate (eGFR) may also be used in place of CrCl)
- \<1.5x institution upper limit of normal OR
- \>= 45 mL/min/1.73 m2 for participant with creatinine levels
- +7 more criteria
You may not qualify if:
- Participants who have had standard-of-care anti-cancer therapy or therapy with investigational agents (e.g., chemotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, or other investigation agents) or large field radiotherapy within 4 weeks prior to treatment initiation.
- Prior therapy with anti- CD40.
- Receiving of live vaccines within 30 days prior to the treatment initiation. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette-Guerin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist(R)) are live attenuated vaccines and are not allowed.
- Major surgery within 4 weeks prior to treatment initiation.
- Active central nervous system metastases and/or carcinomatous meningitis.
- HIV-infected participants.
- History of (non-infectious) pneumonitis or current pneumonitis.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs or other agents used in study, such as nivolumab, dacetuzumab, APX005M, ADC-1013.
- Prior invasive malignancies within the past 3 years prior to treatment initiation (with the exception of non-melanoma skin cancers, non-invasive bladder cancer, or localized prostate cancer for whom systemic therapy is not required).
- Any medical condition that requires chronic systemic steroid therapy, or any other form of immunosuppressive medication (inhaled and topical steroids are permitted).
- Fridericia's corrected QT interval (QTcF) \>= 480 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome.
- Participants who were not able to tolerate prior immune checkpoint inhibitor therapy.
- Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnancy.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Tim F Greten, M.D.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 8, 2023
First Posted
May 9, 2023
Study Start
May 8, 2024
Primary Completion (Estimated)
June 1, 2040
Study Completion (Estimated)
June 1, 2042
Last Updated
March 24, 2026
Record last verified: 2026-01-22
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
- Access Criteria
- Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians.
All IPD recorded in the medical record will be shared with intramural investigators upon request. All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP. All collected IPD will be shared with collaborators under the terms of collaborative agreements.