- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03425461
Anti-SEMA4D Monoclonal Antibody VX15/2503 With Nivolumab or Ipilimumab in Treating Patients With Stage III or IV Melanoma
Phase I Study Combining an Anti-SEMA4D Antibody VX15/2503 With Checkpoint Inhibitors for Patients With Advanced Melanoma Who Have Progressed on Prior Anti-PD1/L1 Based Therapies
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of the combination of anti-SEMA4D monoclonal antibody VX15/2503 (anti-SEMA4D VX15/2503) with nivolumab, or ipilimumab, in melanoma patients who have progressed on anti-PD1/L1 based checkpoint inhibitors.
II. To determine the recommended phase II dose and schedule of the combination of anti-SEMA4D VX15/2503 with nivolumab, or ipilimumab, in melanoma patients who have progressed on anti-PD1/L1 based checkpoint inhibitors.
SECONDARY OBJECTIVES:
I. Define the adverse event profile for the agent combinations and determine attribution (i.e. drug related adverse events [AEs]); II. To evaluate clinical response of patients treated with maximum tolerated dose (MTD) or maximum administered dose (MAD) of the combination of anti-SEMA4D with nivolumab, or ipilimumab.
III. To evaluate whether adding anti-SEMA4D to PD1 or CTLA-4 blockade can increase T-cell infiltration into tumors and whether change in T-cell infiltration is associated with response.
OUTLINE: This is a dose-escalation study of anti-SEMA4D monoclonal antibody VX15/2503. Patients are randomized to 1 of 2 arms.
ARM A: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 intravenously (IV) over 60 minutes and nivolumab IV over 30 minutes every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and ipilimumab IV over 30 minutes every 21 days for courses 1-4, then receive anti-SEMA4D monoclonal antibody VX15/2503 every 28 days for subsequent courses for up to 12 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 12 weeks for 2 years, every 6 months for 3 years, then annually thereafter.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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California
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Los Angeles, California, United States, 90095
- UCLA / Jonsson Comprehensive Cancer Center
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Utah
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Salt Lake City, Utah, United States, 84112
- University of Utah Huntsman Cancer Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients with histologically confirmed unresectable stage III or stage IV metastatic melanoma, who have not been previously treated with a SEMA4D antibody and have had prior anti-PD1/PDL1 inhibitors with documented progression; patient may have or not have prior anti-CTLA4 treatments
- Measurable disease per RECIST v. 1.1 criteria using imaging scans, or peripheral lesions that can be adequately documented with a picture and a ruler even if they do not meet RECIST criteria.
- Patients must have non-target lesion accessible for sequential biopsy (core needle biopsy or excision preferred, fine needle aspiration not eligible)
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Women of child-bearing potential must have a negative serum pregnancy test within 24 hour of initiation of dosing and must agree to use an effective form of contraception during the study from the time of the negative pregnancy test up to 6 months after the last dose of study drug. Effective forms of contraception include abstinence, hormonal contraceptive in conjunction with a barrier method, or a double barrier method. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for >= 1 year. Fertile men must also agree to use an effective method of birth control while on study drug and up to 6 months after the last dose of study drug
- Patients must have fully recovered from the effects of any major surgery or significant traumatic injury within 14 days of course 1 day 1 (C1D1)
- Absolute neutrophil count >= 1 X 10^9/L
- Hemoglobin (Hgb) > 8 g/dL
- Platelet count >= 75 X 10^9/L
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 X upper limit of normal (ULN) or < 5 X ULN in the presence of liver metastases
- Bilirubin =< 3 X ULN or < 5 X ULN in the presence of liver metastases
- Creatinine =< 3 X ULN or calculated creatinine clearance (CrCl) > 30 mL/min using Cockcroft- Gault formula
- Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements
Exclusion Criteria:
- Active secondary malignancy, unless the malignancy is not expected to interfere with the evaluation of safety and is approved by the Medical Monitor.
- Investigational drug use within 28 days of C1D1
- Chemotherapy, targeted therapy, growth factors or radiation therapy within 14 days of C1D1
- Systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to registration
History of any of the following toxicities associated with a prior immunotherapy:
- Grade >= 3 immune mediated adverse event that was considered related to previous immunotherapy and required immune suppressive therapy. It is acceptable to allow patients with Grade 3 ophthalmologic immune-mediated events that improved to Grade 1 within 2 weeks after topical therapy only, and patients with Grade 3 endocrine immune-mediated events that did not experience symptoms lasting > 6 weeks and are not requiring > 7.5mg prednisone or equivalent per day.
- Immune mediated adverse event that was considered related to previous immunotherapy and is still > grade 1 with immune suppressive therapy
- • Any active immune-mediated adverse events requiring ongoing immune suppressive therapy (hormone replacement therapy is permitted).
- Patients with known active central nervous system (CNS) lesions are excluded (i.e., those with radiographically unstable, symptomatic lesions). However, patients treated with stereotactic therapy or surgery are eligible if they remain without evidence of disease progression in the brain for 14 days.
- Major surgery within 14 days of registration
- Has received a live vaccine within 28 days prior to registration
- A known active and clinically significant bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness (human immunodeficiency virus [HIV] testing is not required), including patients who have an active infection requiring systemic therapy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Arm A (anti-SEMA4D VX15/2503, nivolumab)
ARM A: Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and nivolumab IV over 30 minutes every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Given IV
Other Names:
Correlative studies
Given IV
Other Names:
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EXPERIMENTAL: Arm B (anti-SEMA4D VX15/2503, ipilimumab)
Patients receive anti-SEMA4D monoclonal antibody VX15/2503 IV over 60 minutes and ipilimumab IV over 30 minutes every 21 days for courses 1-4, then receive anti-SEMA4D monoclonal antibody VX15/2503 every 28 days for subsequent courses for up to 12 months in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum tolerated dose of anti-SEMA4D monoclonal antibody VX15/2503 determined by dose limiting toxicity assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame: Up to 21 days
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Simple descriptive statistics will be used to summarize toxicities observed at each monitoring visit through the treatment and follow up period such as absolute neutrophil count), severity (by Toxicity Table) and nadir or maximum values for the laboratory measures, time of onset (i.e.
course number), duration, and reversibility or outcome.
Tables will be created to summarize these toxicities and side effects by dose and by course.
Baseline information (e.g. the extent of prior therapy) and demographic information will be presented, as well, to describe the patients treated in this pilot study.
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Up to 21 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Antitumor activity assessed using tumor response
Time Frame: Up to 5 years
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Potential objective responses classifications (complete response [CR], partial response [PR] and stable disease) to this combinatorial immunotherapy will be defined and recorded following Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, immune related response criterion (irRC) and immune related RECIST (irRECIST) criteria.
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Up to 5 years
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Duration of response
Time Frame: From the time measurement criteria is met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented up to 5 years
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From the time measurement criteria is met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented up to 5 years
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Frequency of tumor measurements
Time Frame: Up to 5 years
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Up to 5 years
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Incidence of adverse events based on the Common Toxicity Criteria version 4.0
Time Frame: Up to 2 years
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Adverse events will be tabulated by type, severity, and the frequency and proportion of subjects experiencing the event.
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Up to 2 years
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Response for in-transit metastasis
Time Frame: Up to 5 years
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Response will be assessed, taking the measurement from pictures with a built-in ruler.
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Up to 5 years
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
T cell Infiltration
Time Frame: Baseline and 4 weeks after treatment starts
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Will be analyzed using quantitative digital pathology.
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Baseline and 4 weeks after treatment starts
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T cell receptor (TCR) clonality in tumors
Time Frame: Baseline and 4 weeks after treatment starts
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Will analyze TCR clonality by deep sequencing the TCR Vbeta complementarity-determining region (CDR) region using the ImmunoSeq assay from Adaptive Biotech.
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Baseline and 4 weeks after treatment starts
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Tumor immune microenvironment
Time Frame: Baseline and 4 weeks after treatment starts
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Will be assessed using immunohistochemistry and analyzed using quantitative digital pathology.
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Baseline and 4 weeks after treatment starts
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Collaborators and Investigators
Investigators
- Principal Investigator: Antoni Ribas, MD, PhD, University of California, Los Angeles
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Melanoma
- Skin Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Immunologic Factors
- Immune Checkpoint Inhibitors
- Antibodies
- Nivolumab
- Immunoglobulins
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
- Ipilimumab
Other Study ID Numbers
- 17-001570 (OTHER: UCLA / Jonsson Comprehensive Cancer Center)
- P30CA016042 (U.S. NIH Grant/Contract)
- NCI-2017-02395 (REGISTRY: CTRP (Clinical Trial Reporting Program))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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