search
Back to results

VX15/2503 With or Without Ipilimumab and/or Nivolumab in Patients With Resectable Stage IIIB-D Melanoma

Primary Purpose

Pathologic Stage IIIB Cutaneous Melanoma AJCC v8, Pathologic Stage IIIC Cutaneous Melanoma AJCC v8, Pathologic Stage IIID Cutaneous Melanoma AJCC v8

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ipilimumab
Nivolumab
VX15/2503
Surgery
Sponsored by
Emory University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pathologic Stage IIIB Cutaneous Melanoma AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Stage IIIB, IIIC, IIID histologically-proven melanoma.

    • Cancer confirmed to be surgically resectable, with surgery evaluation with planned prior to resection.
    • No prior immunotherapy with cytotoxic T-lymphocyte associated protein-4 (CTLA-4), anti programmed cell death-1 (PD-1) or VX15/2503. Prior interferon (at least 1 year prior to consent) will be allowed.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • Absolute neutrophil count ≥ 1,500 cells/µL.
  • Platelets ≥ 100,000/µL.
  • Hemoglobin ≥ 9.0g/dL (may receive packed red blood cells [PRBC] transfusion).
  • Total bilirubin ≤ 1.5 x the upper limit of normal (ULN).
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN.
  • Albumin ≥ 3.0 g/dL.
  • Serum creatinine ≤ 1.5 x ULN OR calculated creatinine clearance of ≥ 50 mL/min using Cockcroft-Gault formula.
  • International normalized ration (INR) ≤ 1.5. Anticoagulation is allowed only with low molecular weight heparin (LMWH). Patient receiving LMW heparin on stable therapeutic dose for more than 2 weeks or with factor Xa level < 1.1 U/mL are allowed on the trial.
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
  • Ability to understand and willingness to sign a written informed consent document.
  • Female subjects of childbearing potential must agree to use adequate contraception (at least one highly effective method and one additional method of birth control at the same time or complete abstinence) prior to study entry, for the duration of study treatment and 5 months after last dose of study treatment.
  • Male subjects must agree to use adequate contraception (at least one highly effective method and one additional method of birth control at the same time or complete abstinence) prior to study entry, for the duration of study treatment and 7 months after last dose of study treatment.
  • Female subjects of childbearing age must have a negative serum pregnancy test at study entry.

Exclusion Criteria:

  • Determined not to be a surgical candidate due to medical co-morbidities.
  • Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation).
  • Prior organ allograft or allogeneic bone marrow transplantation.
  • Subjects with active or history of immune mediated pneumonitis, colitis, hepatitis, endocrinopathy, nephritis, or skin reactions as these patients may be at increased risk for developing immune therapy-induced exacerbation or recurrence of their immune mediated disease, potentially delaying surgery.
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Women who are pregnant or lactating.
  • Uncontrolled intercurrent illness including, but not limited to, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure (NYHA class III or IV), unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
  • Clinical evidence of bleeding diathesis or coagulopathy.
  • Patients with prior malignancies, including pelvic cancer, are eligible if they have been disease free for > 5 years. Patients with prior non-melanoma skin cancers and in situ carcinomas are eligible provided there was complete removal.
  • Active bacterial or fungal infections requiring systemic treatment within 7 days of treatment.
  • Use of other investigational drugs (drugs not marked for any indication) within 28 days or at least 5 half-lives (whichever is longer) before study drug administration.
  • History of severe hypersensitivity reactions to other monoclonal antibodies.
  • Non-oncology vaccines within 28 days prior to or after any dose of ipilimumab.
  • Prisoners and subjects who are compulsory detained.
  • Patients with rapidly progressive disease.

Sites / Locations

  • Emory University Hospital/Winship Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Active Comparator

Arm Label

A (VX15/2503, nivolumab, surgery)

B (VX15/2503, ipilimumab, surgery)

C (VX15/2503, nivolumab, ipilimumab, surgery)

D (nivolumab, surgery)

E (surgery)

Arm Description

Participants receive VX15/2503 (pepinemab) IV over 60 minutes and nivolumab IV over 30 minutes on days 1 and 21 and undergo surgery between days 35-49.

Participants receive VX15/2503 (pepinemab) IV over 60 minutes and ipilimumab IV over 30 minutes on days 1 and 21 and undergo surgery between days 35-49.

Participants receive VX15/2503 (pepinemab) IV over 60 minutes, nivolumab IV over 30 minutes, and ipilimumab IV over 30 minutes on days 1 and 21 and undergo between days 35-49.

Participants receive nivolumab IV over 30 minutes on days 1 and 21 and undergo between days 35-49.

Participants undergo surgery.

Outcomes

Primary Outcome Measures

Biomarker parameter analysis: extent of cluster of differentiation 8 (CD8)+ T cell infiltration between experimental groups following treatment
The two-sample t-test will be used to compare the change in CD8+ T cell infiltration after treatment between each experimental group (Cohort A, B, C, and D) and the control group (cohort E), respectively.

Secondary Outcome Measures

Incidence of adverse events assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Descriptive statistics for worst grade of each laboratory parameter by the NCI CTCAE scale version 4.0 at baseline and follow-up will be presented.
Response rate
For participants to be considered evaluable for efficacy, they must have completed the treatment and have a baseline tumor assessment. Response rate will be calculated as proportion (responders/total participants).
Overall survival (OS)
For overall survival, death from any cause will be defined as the event.
Progression-free survival (PFS)
Progression or death from any cause will be defined as the event.

Full Information

First Posted
December 6, 2018
Last Updated
May 2, 2023
Sponsor
Emory University
Collaborators
Bristol-Myers Squibb, Vaccinex Inc., National Institutes of Health (NIH), National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT03769155
Brief Title
VX15/2503 With or Without Ipilimumab and/or Nivolumab in Patients With Resectable Stage IIIB-D Melanoma
Official Title
Pilot Integrated Biomarker Study of VX15/2503 in Combination With Ipilimumab or Nivolumab in Patients With Resectable Metastatic Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 13, 2018 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2031 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
Collaborators
Bristol-Myers Squibb, Vaccinex Inc., National Institutes of Health (NIH), National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This pilot phase I trial studies how well VX15/2503 (pepinemab) with or without ipilimumab and/or nivolumab work in treating participants with stage IIIB-D melanoma that can be removed by surgery. Monoclonal antibodies, such as VX15/2503, ipilimumab, and nivolumab may interfere with the ability of tumor cells to grow and spread.
Detailed Description
PRIMARY OBJECTIVE: I. Evaluate the effect of VX15/2503 (pepinemab) in combination with immune checkpoint inhibitors on T cell infiltrate into the tumor microenvironment in involved and uninvolved lymph nodes and peripheral blood. SECONDARY OBJECTIVES: I. Evaluate the effect of VX15/2503 in combination with immune checkpoint inhibitors on the immune profile of involved and uninvolved lymph nodes and peripheral blood. II. Assess safety and tolerability of profile and tolerability of single agent VX15/2503 to the combination of VX15/2503 and immune checkpoint inhibitors in patients with resectable metastatic melanoma. III. Document pathologic response rates of single agent VX15/2503 and combination VX15/2503 and immune checkpoint inhibitors in patients with resectable melanoma. IV. Compare pathologic response to radiographic response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria in patients receiving single agent VX15/2503 and combination VX15/2503 and immune checkpoint inhibitors in patients with resectable melanoma. OUTLINE: Participants are assigned to 1 of 5 arms. ARM I: Participants receive VX15/2503 intravenously (IV) over 60 minutes and nivolumab IV over 30 minutes on days 1 and 21 and undergo surgery between days 35-49. ARM II: Participants receive VX15/2503 IV over 60 minutes and ipilimumab IV over 30 minutes on days 1 and 21 and undergo surgery between days 35-49. ARM III: Participants receive VX15/2503 IV over 60 minutes, nivolumab IV over 30 minutes, and ipilimumab IV over 30 minutes on days 1 and 21 and undergo between days 35-49. ARM IV: Participants nivolumab IV over 30 minutes on days 1 and 21 and undergo between days 35-49. ARM V: Participants undergo surgery. After completion of study treatment, participants are followed up at 90 days, every 12 weeks for 2 years, every 6 months for 3 years, then annually up to 10 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pathologic Stage IIIB Cutaneous Melanoma AJCC v8, Pathologic Stage IIIC Cutaneous Melanoma AJCC v8, Pathologic Stage IIID Cutaneous Melanoma AJCC v8

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A (VX15/2503, nivolumab, surgery)
Arm Type
Experimental
Arm Description
Participants receive VX15/2503 (pepinemab) IV over 60 minutes and nivolumab IV over 30 minutes on days 1 and 21 and undergo surgery between days 35-49.
Arm Title
B (VX15/2503, ipilimumab, surgery)
Arm Type
Experimental
Arm Description
Participants receive VX15/2503 (pepinemab) IV over 60 minutes and ipilimumab IV over 30 minutes on days 1 and 21 and undergo surgery between days 35-49.
Arm Title
C (VX15/2503, nivolumab, ipilimumab, surgery)
Arm Type
Experimental
Arm Description
Participants receive VX15/2503 (pepinemab) IV over 60 minutes, nivolumab IV over 30 minutes, and ipilimumab IV over 30 minutes on days 1 and 21 and undergo between days 35-49.
Arm Title
D (nivolumab, surgery)
Arm Type
Experimental
Arm Description
Participants receive nivolumab IV over 30 minutes on days 1 and 21 and undergo between days 35-49.
Arm Title
E (surgery)
Arm Type
Active Comparator
Arm Description
Participants undergo surgery.
Intervention Type
Biological
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
BMS-734016, MDX-010, MDX-CTLA4, Yervoy
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
VX15/2503
Other Intervention Name(s)
moAb VX15/2503, Pepinemab
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Surgery
Intervention Description
Undergo therapeutic conventional surgery
Primary Outcome Measure Information:
Title
Biomarker parameter analysis: extent of cluster of differentiation 8 (CD8)+ T cell infiltration between experimental groups following treatment
Description
The two-sample t-test will be used to compare the change in CD8+ T cell infiltration after treatment between each experimental group (Cohort A, B, C, and D) and the control group (cohort E), respectively.
Time Frame
Up to 10 years after study start
Secondary Outcome Measure Information:
Title
Incidence of adverse events assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Description
Descriptive statistics for worst grade of each laboratory parameter by the NCI CTCAE scale version 4.0 at baseline and follow-up will be presented.
Time Frame
Up to 8 weeks after surgery
Title
Response rate
Description
For participants to be considered evaluable for efficacy, they must have completed the treatment and have a baseline tumor assessment. Response rate will be calculated as proportion (responders/total participants).
Time Frame
Up to 10 years after study start
Title
Overall survival (OS)
Description
For overall survival, death from any cause will be defined as the event.
Time Frame
Assessed up to 10 years after study start
Title
Progression-free survival (PFS)
Description
Progression or death from any cause will be defined as the event.
Time Frame
Assessed up to 10 years after study start

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Stage IIIB, IIIC, IIID histologically-proven melanoma. Cancer confirmed to be surgically resectable, with surgery evaluation with planned prior to resection. No prior immunotherapy with cytotoxic T-lymphocyte associated protein-4 (CTLA-4), anti programmed cell death-1 (PD-1) or VX15/2503. Prior interferon (at least 1 year prior to consent) will be allowed. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Absolute neutrophil count ≥ 1,500 cells/µL. Platelets ≥ 100,000/µL. Hemoglobin ≥ 9.0g/dL (may receive packed red blood cells [PRBC] transfusion). Total bilirubin ≤ 1.5 x the upper limit of normal (ULN). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN. Albumin ≥ 3.0 g/dL. Serum creatinine ≤ 1.5 x ULN OR calculated creatinine clearance of ≥ 50 mL/min using Cockcroft-Gault formula. International normalized ration (INR) ≤ 1.5. Anticoagulation is allowed only with low molecular weight heparin (LMWH). Patient receiving LMW heparin on stable therapeutic dose for more than 2 weeks or with factor Xa level < 1.1 U/mL are allowed on the trial. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Ability to understand and willingness to sign a written informed consent document. Female subjects of childbearing potential must agree to use adequate contraception (at least one highly effective method and one additional method of birth control at the same time or complete abstinence) prior to study entry, for the duration of study treatment and 5 months after last dose of study treatment. Male subjects must agree to use adequate contraception (at least one highly effective method and one additional method of birth control at the same time or complete abstinence) prior to study entry, for the duration of study treatment and 7 months after last dose of study treatment. Female subjects of childbearing age must have a negative serum pregnancy test at study entry. Exclusion Criteria: Determined not to be a surgical candidate due to medical co-morbidities. Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation). Prior organ allograft or allogeneic bone marrow transplantation. Subjects with active or history of immune mediated pneumonitis, colitis, hepatitis, endocrinopathy, nephritis, or skin reactions as these patients may be at increased risk for developing immune therapy-induced exacerbation or recurrence of their immune mediated disease, potentially delaying surgery. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Women who are pregnant or lactating. Uncontrolled intercurrent illness including, but not limited to, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure (NYHA class III or IV), unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study. Clinical evidence of bleeding diathesis or coagulopathy. Patients with prior malignancies, including pelvic cancer, are eligible if they have been disease free for > 5 years. Patients with prior non-melanoma skin cancers and in situ carcinomas are eligible provided there was complete removal. Active bacterial or fungal infections requiring systemic treatment within 7 days of treatment. Use of other investigational drugs (drugs not marked for any indication) within 28 days or at least 5 half-lives (whichever is longer) before study drug administration. History of severe hypersensitivity reactions to other monoclonal antibodies. Non-oncology vaccines within 28 days prior to or after any dose of ipilimumab. Prisoners and subjects who are compulsory detained. Patients with rapidly progressive disease.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Lowe, MD, MA
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory University Hospital/Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States

12. IPD Sharing Statement

Learn more about this trial

VX15/2503 With or Without Ipilimumab and/or Nivolumab in Patients With Resectable Stage IIIB-D Melanoma

We'll reach out to this number within 24 hrs