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

NCT03425461 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: 17-001570NCI-2017-02395P30CA016042
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (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

  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.

  Up to 21 days

Secondary Outcomes (5)

• Antitumor activity assessed using tumor response

  Up to 5 years

• Duration of response

  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

• Frequency of tumor measurements

  Up to 5 years

• Incidence of adverse events based on the Common Toxicity Criteria version 4.0

  Up to 2 years

• Response for in-transit metastasis

  Up to 5 years

Other Outcomes (3)

• T cell Infiltration

  Baseline and 4 weeks after treatment starts

• T cell receptor (TCR) clonality in tumors

  Baseline and 4 weeks after treatment starts

• Tumor immune microenvironment

  Baseline and 4 weeks after treatment starts

Study Arms (2)

Arm A (anti-SEMA4D VX15/2503, nivolumab)

EXPERIMENTAL

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; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Other: Pharmacological Study

Arm B (anti-SEMA4D VX15/2503, ipilimumab)

EXPERIMENTAL

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; Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Anti-SEMA4D Monoclonal Antibody VX15/2503 BIOLOGICAL

Given IV

Also known as: moAb VX15/2503, VX15/2503

Arm A (anti-SEMA4D VX15/2503, nivolumab); Arm B (anti-SEMA4D VX15/2503, ipilimumab)

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Arm B (anti-SEMA4D VX15/2503, ipilimumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (anti-SEMA4D VX15/2503, nivolumab); Arm B (anti-SEMA4D VX15/2503, ipilimumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Arm A (anti-SEMA4D VX15/2503, nivolumab)

Pharmacological Study OTHER

Correlative studies

Arm A (anti-SEMA4D VX15/2503, nivolumab); Arm B (anti-SEMA4D VX15/2503, ipilimumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Bristol-Myers Squibb: collaborator
• Vaccinex Inc.: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Study Officials

• Antoni Ribas, MD, PhD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2018
• First Posted: February 7, 2018
• Study Start: June 14, 2018
• Primary Completion: March 4, 2021
• Study Completion: March 4, 2021
• Last Updated: April 2, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)