MelanomaPhase 1NCT03329950
A Study of CDX-1140 (CD40) as Monotherapy or in Combination in Patients With Advanced Malignancies
A Phase 1 study testing CDX-1140, CDX-301 and pembrolizumab in people with Melanoma and Non-small Cell Lung Cancer, run by Celldex Therapeutics at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Non-small Cell Lung Cancer, Breast Cancer
- What is being tested?
- CDX-1140, CDX-301 and pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 132 participants
- Where
- 11 sitesUnited States
- Study dates
- 1 Dec 2017to 13 Sep 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Additional Inclusion Criteria for Part 1:
- Advanced diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, or indolent B-cell lymphoma are also eligible.
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- Lymphoma patients must have received ≥ 1 prior systemic therapy
- Additional Inclusion Criteria for Part 3:
- 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
- Additional Inclusion Criteria for Part 4:
- 1. Patients must have metastatic pancreatic adenocarcinoma, and have not received previous treatment in a metastatic setting
Who cannot join
- 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.
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- 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.
- Additional Exclusion Criteria for lymphoma patients in Part 1:
- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Northside Hospital, Inc.
Atlanta, Georgia, 30342
Georgia Cancer Center at Augusta University
Augusta, Georgia, 30912
Gabrail Cancer Center Research LLC
Canton, Ohio, 44718
Houston Methodist
Houston, Texas, 77030
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Oncology Hematology West, PC dba Nebraska Cancer Specialists
Omaha, Nebraska, 68130
Abramson Cancer Center at the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Providence Portland Medical Center
Portland, Oregon, 97213
Rhode Island Hospital (RIH) The Miriam Hospital (TMH)
Providence, Rhode Island, 02903
HonorHealth Research Insititute
Scottsdale, Arizona, 85258
About this study
Official title: 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.
Read the 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.
- Conditions
- Melanoma, Non-small Cell Lung Cancer, Breast Cancer, Gastric Cancer, Renal Cell Carcinoma, Ovarian Cancer
- Being tested
- CDX-1140, CDX-301, pembrolizumab, Chemotherapy
- 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
- Medical subject headings
- Melanoma, Carcinoma, Non-Small-Cell Lung, Breast Neoplasms, Stomach Neoplasms, Carcinoma, Renal Cell, Ovarian Neoplasms, Cholangiocarcinoma, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CDX-1140Drug
CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.
CDX-301Drug
CDX-301 will be injected once a day for five days before Cycles 1 and 2.
pembrolizumabDrug
Also called KEYTRUDA®
pembrolizumab will be administered every 3 weeks.
ChemotherapyDrug
Gemcitabine and Nab-paclitaxel will be administered on Day 1, Day 8 and Day 15 of each 4 week Cycle.
| Study group | Role | What they receive |
|---|---|---|
| CDX-1140 | Experimental | Part 1: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, intolerance, or two years of treatment. Receives: Drug: CDX-1140 |
| CDX-1140 and CDX-301 | Experimental | 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. Receives: Drug: CDX-1140; Drug: CDX-301 |
| CDX-1140 and pembrolizumab | Experimental | 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. Receives: Drug: CDX-1140; Drug: pembrolizumab |
| CDX-1140 and chemotherapy | Experimental | 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. Receives: Drug: CDX-1140; Drug: Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From first dose through 30 days after last dose
Secondary outcomes (7)
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).
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Prior to each study treatment, multiple timepoints after each study treatment, and at treatment discontinuation up to approximately 1-3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start1 Dec 2017
- Primary completion13 Sep 2022
- Study completion13 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 132 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celldex Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03329950
- Sponsor's protocol ID
- CDX1140-01
- Other IDs
- KEYNOTE-A23
- Status last verified
- Mar 2024
- First submitted
- 23 Oct 2017
- Last updated
- 28 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of CDX-1140 as Monotherapy or in Combination in Patients With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT03329950
- Acronym / sponsor ID
- CDX1140-01
- Conditions
- Melanoma, Non-small Cell Lung Cancer, Breast Cancer, Gastric Cancer, Renal Cell Carcinoma, Ovarian Cancer
- Keywords
- CDX-1140, Solid Tumors, Liver Cancer, GI Cancer, Kidney Cancer, Celldex, Monoclonal, Antibody
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 132 participants (actual)
- Lead sponsor
- Celldex TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 1 Dec 2017 (actual)
- Primary completion
- 13 Sep 2022 (actual)
- Study completion
- 13 Sep 2022 (actual)
- First posted
- 6 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| CDX-1140 | Experimental | Drug: CDX-1140Part 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 | Experimental | Drug: CDX-1140, Drug: CDX-301Part 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 | Experimental | Drug: CDX-1140, Drug: pembrolizumabPart 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 | Experimental | Drug: CDX-1140, Drug: ChemotherapyPart 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CDX-1140CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3. | Drug | CDX-1140, CDX-1140 and CDX-301, CDX-1140 and chemotherapy, CDX-1140 and pembrolizumab |
| CDX-301CDX-301 will be injected once a day for five days before Cycles 1 and 2. | Drug | CDX-1140 and CDX-301 |
| pembrolizumabAlso: KEYTRUDA®pembrolizumab will be administered every 3 weeks. | Drug | CDX-1140 and pembrolizumab |
| ChemotherapyGemcitabine and Nab-paclitaxel will be administered on Day 1, Day 8 and Day 15 of each 4 week Cycle. | Drug | CDX-1140 and chemotherapy |
Primary outcome
Safety and Tolerability of CDX-1140 as assessed by CTCAE v5.0
Time frame: From first dose through 30 days after last dose
The rates of drug-related adverse events will be summarized and maximum tolerated dose will be determined.
7 secondary outcomes
Objective Response Rate
Time frame: Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years.
Clinical benefit rate
Time frame: Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years
Duration of Response
Time frame: First occurrence of a documented objective response to disease progression or death (up to approximately 1-3 years)
Progression-free survival
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
Time frame: The time from start of study drug to death from any cause (up to approximately 1-3 years)
Immunogenicity evaluation
Time frame: Prior to each dose of study treatment and at treatment discontinuation, up to approximately 1-3 years
Pharmacokinetic evaluation
Time frame: Prior to each study treatment, multiple timepoints after each study treatment, and at treatment discontinuation up to approximately 1-3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CDX-1140, CDX-301 and pembrolizumab in people with Melanoma and Non-small Cell Lung Cancer, run by Celldex Therapeutics at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability of CDX-1140 as assessed by CTCAE v5.0 (time frame: From first dose through 30 days after last dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2024.