CancerPhase 1NCT04059588
A Study Investigating the Safety and Tolerability of an Immune Treatment in Cancer Patients With Lesions to the Skin
A Phase 1 study testing 2141 V-11 in people with Cancer and Solid Tumor, run by Rockefeller University at 1 site in United States.
Trial summary
The purpose of this study is to test the safety and tolerability of 2141-V11 in people who have cancer that does not respond to standard treatment and who have skin lesions (skin tumors) associated with their cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Solid Tumor, Cancer of Skin
- What is being tested?
- 2141 V-11
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jan 2020to 13 Mar 2023
- 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
- Age > 18 years old
- Must have measurable or evaluable metastatic disease (at least more than 1 lesion) as evidenced by physical exam or imaging
- Must have an identifiable metastatic lesion of the skin, subcutaneous tissue, or lymph node amenable to intratumoral injection. This includes all solid tumors as well as metastatic melanoma and/or melanoma with in-transit metastases.
- ECOG performance status < 1
- Histologically confirmed diagnosis of refractory or relapsed metastatic disease
- Required values for screening laboratory tests:
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- Absolute neutrophil count (ANC) > 1000/mm3 independent of growth factor support
- Platelets > 75,000/mm3
- Hemoglobin > 8 g/dl
- Creatinine clearance > 40 ml/min for the dose-escalation phase, >25 ml/min in dose expansion phase (if safety data from dose escalation indicate this is possible)
- AST/ALT < 3 x ULN
- Bilirubin < 1.5 x ULN (except for participants with Gilbert's Syndrome or of non-hepatic origin)
- Patients must have refractory or relapsed disease and have must have exhausted all standard-of-care therapy for their disease
- Must be at least 4 weeks since treatment with checkpoint inhibitors or other antibody-based therapy or investigational agents
- Must be at least 2 weeks since chemotherapy, targeted small molecule therapy, cytokine therapy, or radiation therapy, and be recovered from any clinically significant toxicity experienced during treatment.
- If sexually active male or female, and participating in sexual activity that could lead to pregnancy, agrees to use two effective methods of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom). For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug. Men must agree not to donate sperm during and after the study.
- Female study participants of reproductive potential are defined as pre-menopausal women who have not had a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy). Women are considered menopausal if they have not had a menses for at least 12 months and have a FSH of greater than 40 IU/L or if FSH testing is not available, they have had amenorrhea for 24 consecutive months.
- Women of childbearing potential must have a negative (beta-human chorionic gonadotropin [b-hCG] pregnancy test at screening, as well as a negative pregnancy test prior to each treatment
- Life expectancy greater than 16 weeks (should be evaluated by a prognostic score, e.g., Royal Marsden score).
- Able to comply with the treatment schedule as determined by the participant and the LIP
Who cannot join
- Concurrent anticancer therapy including investigational agents. This includes topical therapeutic agents.
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), risk of pulmonary toxicity, or evidence of active pneumonitis on screening chest CT scan.
- History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen (HBsAg) test at screening.
- Patients with past/resolved hepatitis B virus (HBV) infection (defined as having a negative HBsAg and a positive antibody to hepatitis B core antigen antibody test) are eligible only if polymerase chain reaction is negative for HBV RNA. HBV DNA must be obtained in these patients prior to Cycle 1, Day 1.
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
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- Has spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to screening.
- Vaccinated with live, attenuated viral vaccines within 4 weeks of enrollment.
- Known history of human immunodeficiency virus (HIV) or any uncontrolled active systemic infection.
- Major surgery or a wound that has not fully healed within 4 weeks of enrollment.
- Treatment with an immunosuppressive regimen of corticosteroids or other immunosuppressive medication (e.g., methotrexate, rapamycin) within 30 days of study treatment. Note: patients with adrenal insufficiency may take up to 5 mg of prednisone or equivalent daily. Topical and inhaled corticosteroids in standard doses are allowed.
- Severe infections within 4 weeks prior to Cycle 1, Day 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
- Signs and symptoms of infection within 2 weeks prior to Cycle 1, Day 1.
- Any investigational therapy within 28 days prior to initiation of study treatment. This includes topical or injected agents.
- Significant cardiovascular disease (i.e., NYHA class 3 congestive heart failure; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias.
- Autoimmune disease including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, history of uveitis or other autoimmune disease if clinically significant.
- Patients with clinically active brain metastases are excluded. Patients with stable brain metastasis (with or without intervention) are eligible. Patients with previously irradiated lesions are eligible provided patient is >4 weeks beyond completion of cranial irradiation and >3 weeks of corticosteroid therapy.
- Known history of leptomenigeal disease, patients with metastases to the brain stem, midbrain, pons, or medulla, and patients with metastases with 10 mm of the optic apparatus (optic nerve and chiasm) will be excluded from the study.
- Requires anticoagulation with warfarin or equivalent vitamin K antagonists.
- Has had a pulmonary embolism or any other thromboembolic event within 6 months prior to study entry.
- Prior toxicities from previous cancer therapy, including checkpoint inhibition, that have not regressed to Grade < 1 severity (NCI CTCAE v4.03, or later versions) within 28 days before Cycle 1, Day 1, with the exception of alopecia.
- Active hepatitis C are excluded. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- Any surgical procedure within less than 14 days of the first receipt of study drug. Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of the need for a major surgical procedure during the study other than for diagnosis.
- Pregnant or breast feeding
- Active infection or with a fever >38.5o C within 3 days prior to the first scheduled treatment.
- Any medical history, including laboratory results, deemed by the investigator to be likely to interfere with their participation in the study, or to interfere with the interpretation of the results, or any social condition that, in the opinion of the Investigator, might pose additional risk to the participant or confound the results of the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Dose-escalation Study Investigating the Safety and Tolerability of Intratumoral Injection of an Fc-engineered Anti-CD40 Monoclonal Antibody (2141-V11) in Patients With Cancer
The purpose of this study is to test the safety and tolerability of 2141-V11 in people who have cancer that does not respond to standard treatment and who have skin lesions (skin tumors) associated with their cancer. The study will also test how the body processes and responds to 2141-V11, and if the study drug has cancer fighting activity in people. The study drug activates a naturally occurring protein called CD40. By activating CD40, cells of the immune system are better able to identify and kill cancer cells.
We are testing if injection of 2141-V11 into metastasis to the skin will be safe and well tolerated, and may result in immune activation in patients with solid tumors that have metastasis to the skin.
Read the detailed description
This is a Phase 1 open label, dose-escalation study evaluating the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy of the Fc-engineered variant 2141-V11 in patients with previously treated relapsed or refractory solid tumors and locally advanced or metastatic solid tumors to the skin amenable to intratumoral injection.
There are two parts to the study: a dose-finding stage (Part I), and a dose expansion stage (Part II). Both Part I and Part II of the study will include patients with locally advanced or metastatic cancers of the skin which are not amenable to standard treatment.
A traditional 3 + 3 dose escalation design will be used (Part I). Successive cohorts of participants (3 participants/cohort) will be started on a fixed dose intratumoral injection of 2141V11 at the dose assigned to their cohort. The study drug, 2141-V11, will be dosed once every 3 weeks. The study drug is administered in cycles.
The first group of study participants in Part I will receive the lowest dose of study drug. The next group of study participants will receive the next higher dose. This dosing scheme continues until the maximum tolerated dose is determined. The maximum tolerated dose (MTD) will be defined as 1 dose level below the dose in which DLTs are observed in >33% of the participants.
Participants in Part II of the study will receive the MTD determined from Part 1 (dose escalation) of the study. Part II participants in the study will also receive two vaccinations (KLH and tetanus) to allow monitoring of their immune function.
Participants in both Part I and II can continue to receive cycles of study drug at their assigned dose if they do not experience progression of disease, a serious adverse event, and the study is ongoing.
- Conditions
- Cancer, Solid Tumor, Cancer of Skin
- Being tested
- 2141 V-11
- Keywords
- Solid Tumors, Skin lesions, Immunotherapy, CD40 antibody, Cancer, intratumoral, intralesional, metastases, metastasis
- Medical subject headings
- Neoplasms, Skin Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
2141 V-11Drug
intratumoral injection of 2141-V11
| Study group | Role | What they receive |
|---|---|---|
| Injection of 2141-V11 | Experimental | Open label study drug 2141-V11 at escalating doses until MTD is determined, and expansion utilizing the MTD. Receives: Drug: 2141 V-11 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with treatment-emergent adverse events assessed by NCI CTCAE v4.03
Adverse events
Measured: through study completion, an average of 2 years
Incidence and severity of DLTs reported and their relationship to 2141-V11 administration assessed by NCI CTCAE v4.03
Dose limiting toxities
Measured: through study completion, an average of 2 years
Change from baseline laboratory assessments and toxicities over time in abnormal Complete Blood Count labs and Complete Metabolic Panel labs assessed by SI laboratory reference ranges
Change from baseline laboratory assessments and toxisities over time
Measured: through study completion, an average of 2 years
Changes from baseline in anti-drug antibody (ADA) responses to 2141-V11 exposure over time
Anti-Drug antidoby (ADA) response over time
Measured: through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2019
- Study start16 Jan 2020
- Primary completion13 Mar 2023
- Study completion13 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies 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
- Other
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher dose levels of 2141-V 11 using a standard 3+3 dose-escalation design.
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rockefeller University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Juan Osorio, MD, PhD, Principal investigator, Rockefeller University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04059588
- Sponsor's protocol ID
- DKN-0993
- Status last verified
- Apr 2024
- First submitted
- 7 Aug 2019
- Last updated
- 17 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Osorio JC, Knorr DA, Weitzenfeld P, Yao N, Baez M, DiLillo M, Rahman J, Bromberg J, Postow MA, Ariyan C, Robson ME, Ravetch JV. Intratumoral Fc-optimized agonistic CD40 antibody induces tumor rejection and systemic antitumor immunity in patients with metastatic cancer. Res Sq [Preprint]. 2024 Jun 3:rs.3.rs-4244833. doi: 10.21203/rs.3.rs-4244833/v1.
PubMed 38883779
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Dose-escalation Study Investigating the Safety and Tolerability of Intratumoral Injection of an Fc-engineered Anti-CD40 Monoclonal Antibody (2141-V11) in Patients With Cancer
- ClinicalTrials.gov ID
- NCT04059588
- Acronym / sponsor ID
- DKN-0993
- Conditions
- Cancer, Solid Tumor, Cancer of Skin
- Keywords
- Solid Tumors, Skin lesions, Immunotherapy, CD40 antibody, Cancer, intratumoral, intralesional, metastases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Rockefeller UniversityUniversity, hospital or other
- Study start
- 16 Jan 2020 (actual)
- Primary completion
- 13 Mar 2023 (actual)
- Study completion
- 13 Mar 2023 (actual)
- First posted
- 16 Aug 2019 (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.
The purpose of this study is to test the safety and tolerability of 2141-V11 in people who have cancer that does not respond to standard treatment and who have skin lesions (skin tumors) associated with their cancer. The study will also test how the body processes and responds to 2141-V11, and if the study drug has cancer fighting activity in people. The study drug activates a naturally occurring protein called CD40. By activating CD40, cells of the immune system are better able to identify and kill cancer cells.
We are testing if injection of 2141-V11 into metastasis to the skin will be safe and well tolerated, and may result in immune activation in patients with solid tumors that have metastasis to the skin.
Detailed description
This is a Phase 1 open label, dose-escalation study evaluating the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy of the Fc-engineered variant 2141-V11 in patients with previously treated relapsed or refractory solid tumors and locally advanced or metastatic solid tumors to the skin amenable to intratumoral injection.
There are two parts to the study: a dose-finding stage (Part I), and a dose expansion stage (Part II). Both Part I and Part II of the study will include patients with locally advanced or metastatic cancers of the skin which are not amenable to standard treatment.
A traditional 3 + 3 dose escalation design will be used (Part I). Successive cohorts of participants (3 participants/cohort) will be started on a fixed dose intratumoral injection of 2141V11 at the dose assigned to their cohort. The study drug, 2141-V11, will be dosed once every 3 weeks. The study drug is administered in cycles.
The first group of study participants in Part I will receive the lowest dose of study drug. The next group of study participants will receive the next higher dose. This dosing scheme continues until the maximum tolerated dose is determined. The maximum tolerated dose (MTD) will be defined as 1 dose level below the dose in which DLTs are observed in >33% of the participants.
Participants in Part II of the study will receive the MTD determined from Part 1 (dose escalation) of the study. Part II participants in the study will also receive two vaccinations (KLH and tetanus) to allow monitoring of their immune function.
Participants in both Part I and II can continue to receive cycles of study drug at their assigned dose if they do not experience progression of disease, a serious adverse event, and the study is ongoing.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher dose levels of 2141-V 11 using a standard 3+3 dose-escalation design.
| Arm | Type | Receives |
|---|---|---|
| Injection of 2141-V11 | Experimental | Drug: 2141 V-11Open label study drug 2141-V11 at escalating doses until MTD is determined, and expansion utilizing the MTD. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Age > 18 years old
- Must have measurable or evaluable metastatic disease (at least more than 1 lesion) as evidenced by physical exam or imaging
- Must have an identifiable metastatic lesion of the skin, subcutaneous tissue, or lymph node amenable to intratumoral injection. This includes all solid tumors as well as metastatic melanoma and/or melanoma with in-transit metastases.
- ECOG performance status < 1
- Histologically confirmed diagnosis of refractory or relapsed metastatic disease
Key exclusion criteria (26 listed)
- Concurrent anticancer therapy including investigational agents. This includes topical therapeutic agents.
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), risk of pulmonary toxicity, or evidence of active pneumonitis on screening chest CT scan.
- History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen (HBsAg) test at screening.
- Patients with past/resolved hepatitis B virus (HBV) infection (defined as having a negative HBsAg and a positive antibody to hepatitis B core antigen antibody test) are eligible only if polymerase chain reaction is negative for HBV RNA. HBV DNA must be obtained in these patients prior to Cycle 1, Day 1.
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 |
|---|---|---|
| 2141 V-11intratumoral injection of 2141-V11 | Drug | Injection of 2141-V11 |
Primary outcome
Number of patients with treatment-emergent adverse events assessed by NCI CTCAE v4.03
Time frame: through study completion, an average of 2 years
Adverse events
Incidence and severity of DLTs reported and their relationship to 2141-V11 administration assessed by NCI CTCAE v4.03
Time frame: through study completion, an average of 2 years
Dose limiting toxities
Change from baseline laboratory assessments and toxicities over time in abnormal Complete Blood Count labs and Complete Metabolic Panel labs assessed by SI laboratory reference ranges
Time frame: through study completion, an average of 2 years
Change from baseline laboratory assessments and toxisities over time
Changes from baseline in anti-drug antibody (ADA) responses to 2141-V11 exposure over time
Time frame: through study completion, an average of 2 years
Anti-Drug antidoby (ADA) response over time
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 17 Apr 2024.
- Derived from this study: PubMed 38883779Osorio JC, Knorr DA, Weitzenfeld P, Yao N, Baez M, DiLillo M, Rahman J, Bromberg J, Postow MA, Ariyan C, Robson ME, Ravetch JV. Intratumoral Fc-optimized agonistic CD40 antibody induces tumor rejection and systemic antitumor immunity in patients with metastatic cancer. Res Sq [Preprint]. 2024 Jun 3:rs.3.rs-4244833. doi: 10.21203/rs.3.rs-4244833/v1.
- Individual participant dataSharing planned: No
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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.
Juan Osorio, MD, PhD principal investigator
Rockefeller University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 2141 V-11 in people with Cancer and Solid Tumor, run by Rockefeller University at 1 site 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 20 inclusion and 26 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 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Number of patients with treatment-emergent adverse events assessed by NCI CTCAE v4.03 (time frame: through study completion, an average of 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04059588, which also lists 1 linked publication.
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 17 Apr 2024.