ClinicalTrials.gov
ClinicalTrials.gov Menu

Anti-SEMA4D Monoclonal Antibody VX15/2503 With Nivolumab or Ipilimumab in Treating Patients With Stage III or IV Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03425461
Recruitment Status : Recruiting
First Posted : February 7, 2018
Last Update Posted : June 19, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center

Brief Summary:
This randomized pilot phase I trial studies the side effects and best dose of anti-SEMA4D monoclonal antibody VX15/2503 when given together with nivolumab or ipilimumab in treating patients with stage III or IV melanoma. Monoclonal antibodies, such as anti-SEMA4D monoclonal antibody VX15/2503, nivolumab, and ipilimumab, may interfere with the ability of tumor cells to grow and spread.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Stage III Cutaneous Melanoma AJCC v7 Stage IIIA Cutaneous Melanoma AJCC v7 Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7 Biological: Anti-SEMA4D Monoclonal Antibody VX15/2503 Biological: Ipilimumab Other: Laboratory Biomarker Analysis Biological: Nivolumab Other: Pharmacological Study Phase 1

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 14, 2018
Estimated Primary Completion Date : December 1, 2020
Estimated Study Completion Date : December 1, 2021


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.
Biological: Anti-SEMA4D Monoclonal Antibody VX15/2503
Given IV
Other Names:
  • moAb VX15/2503
  • VX15/2503

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Other: Pharmacological Study
Correlative studies

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.
Biological: Anti-SEMA4D Monoclonal Antibody VX15/2503
Given IV
Other Names:
  • moAb VX15/2503
  • VX15/2503

Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies




Primary Outcome Measures :
  1. 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 ]
    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.


Secondary Outcome Measures :
  1. Antitumor activity assessed using tumor response [ Time Frame: Up to 5 years ]
    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.

  2. 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 ]
  3. Frequency of tumor measurements [ Time Frame: Up to 5 years ]
  4. Incidence of adverse events based on the Common Toxicity Criteria version 4.0 [ Time Frame: Up to 2 years ]
    Adverse events will be tabulated by type, severity, and the frequency and proportion of subjects experiencing the event.

  5. Response for in-transit metastasis [ Time Frame: Up to 5 years ]
    Response will be assessed, taking the measurement from pictures with a built-in ruler.


Other Outcome Measures:
  1. T cell Infiltration [ Time Frame: Baseline and 4 weeks after treatment starts ]
    Will be analyzed using quantitative digital pathology.

  2. T cell receptor (TCR) clonality in tumors [ Time Frame: Baseline and 4 weeks after treatment starts ]
    Will analyze TCR clonality by deep sequencing the TCR Vbeta complementarity-determining region (CDR) region using the ImmunoSeq assay from Adaptive Biotech.

  3. Tumor immune microenvironment [ Time Frame: Baseline and 4 weeks after treatment starts ]
    Will be assessed using immunohistochemistry and analyzed using quantitative digital pathology.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 Response Evaluation Criteria in Solid Tumors (RECIST) version (v.) 1.1 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; examples include basal or squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, and isolated elevation of prostate-specific antigen; patients with a completely treated prior malignancy with no evidence of disease for >= 2 years are eligible
  • 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 14 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
    • Immune mediated adverse event that was considered related to previous immunotherapy and is still > grade 1 with immune suppressive therapy
  • Patients with 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 >= 3 weeks
  • Major surgery within 28 days of registration
  • Has received a live vaccine within 28 days prior to registration
  • 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
  • Any of the following within the 12 months prior to registration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack
  • Uncontrolled intercurrent illness
  • History of active ethanol abuse
  • Patients who are imprisoned or under legal guardianship
  • The presence of a medical or psychiatric condition that, in the opinion of the principal investigator, makes the patient inappropriate for inclusion in this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03425461


Locations
United States, California
UCLA / Jonsson Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90095
Contact: Siwen Hu-Lieskovan    310-794-4955    shu-lieskovan@mednet.ucla.edu   
Principal Investigator: Siwen Hu-Lieskovan         
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Siwen Hu-Lieskovan UCLA / Jonsson Comprehensive Cancer Center

Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT03425461     History of Changes
Other Study ID Numbers: 17-001570
NCI-2017-02395 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
17-001570 ( Other Identifier: UCLA / Jonsson Comprehensive Cancer Center )
P30CA016042 ( U.S. NIH Grant/Contract )
First Posted: February 7, 2018    Key Record Dates
Last Update Posted: June 19, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Nivolumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents