Glembatumumab Vedotin, Nivolumab, and Ipilimumab in Treating Patients With Advanced Metastatic Solid Tumors That Cannot Be Removed by Surgery

NCT03326258 | Withdrawn Phase 1 FDA Drug

• 3 other identifiers: NCI-2017-0197910157UM1CA186704
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase Ib/II trial studies the best dose of glembatumumab vedotin when giving together with nivolumab and ipilimumab in treating patients with solid tumor that has spread to other places in the body and cannot be removed by surgery. Monoclonal antibodies, such as glembatumumab vedotin, nivolumab, and ipilimumab, may interfere with the ability of tumor cells to grow and spread.

Conditions

Advanced Malignant Solid Neoplasm; Estrogen Receptor Negative; GPNMB Positive; HER2/Neu Negative; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Progesterone Receptor Negative; Stage III Breast Cancer AJCC v7; Stage III Cutaneous Melanoma AJCC v7; Stage III Uveal Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Uveal Melanoma AJCC v7; Triple-Negative Breast Carcinoma; Unresectable Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• Recommended phase 2 dose for the combination of glembatumumab vedotin and nivolumab (Phase Ib)

  All adverse events and toxicities will be tabulated and reported by type and grade for all dose levels of all treatment combinations and the proportions will be reported with exact 90% binomial confidence intervals.

  Up to 21 days

• Antitumor activity measured by Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST)/Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Phase II)

  Descriptive statistics and graphical analysis will be used to summarize patients' demographic and clinicopathological characteristics, patient safety and efficacy outcomes and correlative markers. Overall response rates will be calculated and 2-sided 90% confidence intervals will also be provided for each cohort.

  Up to 70 days

Secondary Outcomes (7)

• Incidence of adverse events

  Up to 70 days

• Overall response rate

  Up to 70 days

• Clinical benefit rate

  Up to 70 days

• Progression free survival

  Up to 70 days

• Overall survival

  Up to 70 days

Study Arms (1)

Treatment (glembatumumab vedotin, nivolumab, ipilimumab)

EXPERIMENTAL

Patients receive glembatumumab vedotin IV over 90 minutes and nivolumab IV over 60 minutes on day 8 of course 1 and on day 1 of subsequent courses. Patients in melanoma expanded cohort also receive ipilimumab IV over 90 minutes on day 1. Treatment with ipilimumab repeats every 21 days for 4 courses in the absence of disease progression or unaccepted toxicity and courses with glembatumumab vedotin and nivolumab repeat every 21 days in the absence of disease progression or unaccepted toxicity.

Drug: Glembatumumab Vedotin; Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Other: Pharmacological Study

Interventions

Glembatumumab Vedotin DRUG

Given IV

Also known as: Antibody-Drug Conjugate CR011-vcMMAE, CDX-011, CR011-vcMMAE, CR011-vcMMAE Immunotoxin

Treatment (glembatumumab vedotin, nivolumab, ipilimumab)

Ipilimumab BIOLOGICAL

Given IV

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

Treatment (glembatumumab vedotin, nivolumab, ipilimumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (glembatumumab vedotin, nivolumab, ipilimumab)

Nivolumab BIOLOGICAL

Given IV

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

Treatment (glembatumumab vedotin, nivolumab, ipilimumab)

Pharmacological Study OTHER

Correlative studies

Treatment (glembatumumab vedotin, nivolumab, ipilimumab)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective
• For TNBC and solid tumors other than melanoma: GPNMB expression as defined by at least 25% of malignant epithelial cells or tumor stromal cells expression GPNMB at any intensity via central immunohistochemistry on archived or biopsied tumor tissue (as per standard clinical care) from an advanced/metastatic disease site; for melanoma or uveal melanoma cohort: GPNMB testing results will not be required for eligibility assessment
• Patients must have measurable disease, in addition to at least one lesion in a reasonably safe location for study-related biopsies; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) by chest x-ray or as \>= 10 mm (\>= 1 cm) with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Willing to undergo study-related biopsies as noted in study calendar: before treatment, after glembatumumab-only, and after combination therapy
• Prior treatment with immune checkpoint inhibitors or antibody drug conjugates are allowed.
• For cutaneous melanoma cohort, patients should have received PD-1/CTLA-4 targeting therapy in combination and had disease progression
• For all other cohorts including phase Ib dose-finding, patients should have received at least one line of standard non-immunotherapy treatment
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 80%)
• Life expectancy of greater than 12 weeks
• Leukocytes \>= 2,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 75,000/mcL
• Hemoglobin \>= 9.0 g/dL
• Total bilirubin =\< 1.5 x institutional upper limit of normal (except patients with Gilbert syndrome, who can have total bilirubin \< 3.0 mg/dL)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional upper limit of normal (or =\< 5.0 x institutional upper limit of normal in presence of metastatic liver disease)

You may not qualify if:

• Patients who have had systemic therapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy within 2 weeks prior to entering the study
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \>= grade 2 other than alopecia)
• Patients who are receiving any other concurrent investigational agents; those with history of receiving investigational cancer treatment are allowed as long as washout period is fulfilled
• Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression; patients with treated and stable brain metastases will be allowed; controlled brain metastases are defined as no radiographic progression for at least 4 weeks following radiation and/or surgical treatment (or 4 weeks of observation if no intervention is clinically indicated), and off of steroids for at least 2 weeks, and no new or progressive neurological signs and symptoms
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab, glembatumumab vedotin, or other agents used in study; this includes sensitivity to the drugs dolastatin or auristatin
• History of severe hypersensitivity reaction to any monoclonal antibody
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Participants must not have a history of life-threatening toxicity related to prior IO treatment (eg, anti-CTLA-4 or anti-PD-1/PD-L1 treatment or any other antibody or treatment specifically targeting T-cell co-stimulation or immune checkpoint pathways); i) participants with toxicities that are unlikely to recur with standard countermeasures (eg, hormone replacement treatment after adrenal crisis) are eligible
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with nivolumab and glembatumumab vedotin
• Human immunodeficiency virus (HIV) patients should be allowed if otherwise eligible, with the following caveats:
• Undetectable HIV viral load by standard clinical assay
• Willing to remain adherent with antiretroviral therapy that has minimal overlapping toxicity or pharmacokinetic interactions with protocol therapy
• CD4+ T cell counts of 200/mm\^3 or greater
• No acquired immunodeficiency syndrome (AIDS)-defining events other within the past 12 months
• Near normal life expectancy if not for presence of the cancer

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Conditions

Neoplasm Metastasis; Melanoma; Breast Neoplasms; Uveal Melanoma; Triple Negative Breast Neoplasms

Interventions

glembatumumab vedotin; CR011-vcMMAE; Ipilimumab; CTLA-4 Antigen; Nivolumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Breast Diseases; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal 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

• Haeseong Park

  Duke University - Duke Cancer Institute LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2017
• First Posted: October 31, 2017
• Study Start: April 20, 2018
• Primary Completion: April 20, 2018
• Study Completion: April 20, 2018
• Last Updated: July 18, 2018

Record last verified: 2018-05