Clinical Trials /

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

NCT03425461

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 17-001570
  • SECONDARY ID: NCI-2017-02395
  • SECONDARY ID: 17-001570
  • SECONDARY ID: P30CA016042
  • NCT ID: NCT03425461

Conditions

  • 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

Interventions

DrugSynonymsArms
Anti-SEMA4D Monoclonal Antibody VX15/2503moAb VX15/2503, VX15/2503Arm A (anti-SEMA4D VX15/2503, nivolumab)
IpilimumabAnti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, YervoyArm B (anti-SEMA4D VX15/2503, ipilimumab)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoArm A (anti-SEMA4D VX15/2503, nivolumab)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (anti-SEMA4D VX15/2503, nivolumab)ExperimentalARM 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.
  • Anti-SEMA4D Monoclonal Antibody VX15/2503
  • Nivolumab
Arm B (anti-SEMA4D VX15/2503, ipilimumab)ExperimentalPatients 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.
  • Anti-SEMA4D Monoclonal Antibody VX15/2503
  • Ipilimumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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

Measure:Antitumor activity assessed using tumor response
Time Frame:Up to 5 years
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description:
Measure:Frequency of tumor measurements
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Incidence of adverse events based on the Common Toxicity Criteria version 4.0
Time Frame:Up to 2 years
Safety Issue:
Description:Adverse events will be tabulated by type, severity, and the frequency and proportion of subjects experiencing the event.
Measure:Response for in-transit metastasis
Time Frame:Up to 5 years
Safety Issue:
Description:Response will be assessed, taking the measurement from pictures with a built-in ruler.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Jonsson Comprehensive Cancer Center

Last Updated