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Trial record 9 of 25 for:    vx15

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

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ClinicalTrials.gov Identifier: NCT03769155
Recruitment Status : Recruiting
First Posted : December 7, 2018
Last Update Posted : December 17, 2018
Sponsor:
Collaborators:
Bristol-Myers Squibb
Vaccinex Inc.
Information provided by (Responsible Party):
Michael Lowe, Emory University

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.

Condition or disease Intervention/treatment Phase
Pathologic Stage IIIB Cutaneous Melanoma AJCC v8 Pathologic Stage IIIC Cutaneous Melanoma AJCC v8 Pathologic Stage IIID Cutaneous Melanoma AJCC v8 Biological: Ipilimumab Biological: Nivolumab Biological: VX15/2503 Procedure: Surgery Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

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 receive VX15/2503 IV over 60 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Integrated Biomarker Study of VX15/2503 in Combination With Ipilimumab or Nivolumab in Patients With Resectable Metastatic Melanoma
Actual Study Start Date : December 13, 2018
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2031


Arm Intervention/treatment
Experimental: A (VX15/2503, nivolumab, surgery)
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.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Biological: VX15/2503
Given IV
Other Names:
  • moAb VX15/2503
  • Pepinemab

Procedure: Surgery
Undergo therapeutic conventional surgery

Experimental: B (VX15/2503, ipilimumab, surgery)
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.
Biological: Ipilimumab
Given IV
Other Names:
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Biological: VX15/2503
Given IV
Other Names:
  • moAb VX15/2503
  • Pepinemab

Procedure: Surgery
Undergo therapeutic conventional surgery

Experimental: C (VX15/2503, nivolumab, ipilimumab, surgery)
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.
Biological: Ipilimumab
Given IV
Other Names:
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy

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

Biological: VX15/2503
Given IV
Other Names:
  • moAb VX15/2503
  • Pepinemab

Procedure: Surgery
Undergo therapeutic conventional surgery

Experimental: D (VX15/2503, surgery)
Participants receive VX15/2503 (pepinemab) IV over 60 minutes on days 1 and 21 and undergo between days 35-49.
Biological: VX15/2503
Given IV
Other Names:
  • moAb VX15/2503
  • Pepinemab

Procedure: Surgery
Undergo therapeutic conventional surgery

Active Comparator: E (surgery)
Participants undergo surgery.
Procedure: Surgery
Undergo therapeutic conventional surgery




Primary Outcome Measures :
  1. Biomarker parameter analysis: extent of cluster of differentiation 8 (CD8)+ T cell infiltration between experimental groups following treatment [ Time Frame: Up to 10 years after study start ]
    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 :
  1. Incidence of adverse events assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 8 weeks after surgery ]
    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.

  2. Response rate [ Time Frame: Up to 10 years after study start ]
    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).

  3. Overall survival (OS) [ Time Frame: Assessed up to 10 years after study start ]
    For overall survival, death from any cause will be defined as the event.

  4. Progression-free survival (PFS) [ Time Frame: Assessed up to 10 years after study start ]
    Progression or death from any cause will be defined as the event.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (e.g., hormonal or barrier method of birth control; abstinence) for the duration of study treatment and 5 months after last dose of study treatment.
  • Male subjects must agree to use adequate contraception (e.g., condoms; abstinence) 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.

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): NCT03769155


Contacts
Contact: Michael Lowe, MD, MA 404-778-3612 mlowe3@emory.edu

Locations
United States, Georgia
Emory University Hospital/Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Monica Goings    404-778-5141    monica.s.goings@emory.edu   
Contact: Allyson Schmidt    404-727-7099    allyson.schmidt@emory.edu   
Sponsors and Collaborators
Emory University
Bristol-Myers Squibb
Vaccinex Inc.
Investigators
Principal Investigator: Michael Lowe, MD, MA Emory University

Responsible Party: Michael Lowe, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT03769155     History of Changes
Other Study ID Numbers: IRB00104273
NCI-2018-01229 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Winship4400-18 ( Other Identifier: Emory University Hospital/Winship Cancer Institute )
First Posted: December 7, 2018    Key Record Dates
Last Update Posted: December 17, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs