Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Eye Diseases

Rare Diseases

Recurrence

Melanoma

Uveal Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Eye Neoplasms

Uveal Diseases

Intraocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Immunoglobulins

Immunotoxins

Glembatumumab vedotin

Immunoconjugates

Antibodies, Monoclonal

Immunologic Factors

Antineoplastic Agents, Immunological

Patients receive glembatumumab vedotin IV over 90 minutes every 3 weeks in the absence of disease progression or unacceptable toxicity.

Glembatumumab Vedotin

Laboratory Biomarker Analysis

Pharmacological Study

Sapna Patel

This phase II trial studies how well glembatumumab vedotin works in treating patients with middle layer of the wall of the eye (uveal) melanoma that has spread to other parts of the body (metastatic) or has returned at or near the same place after a period of time during which the cancer could not be detected (locally recurrent). Glembatumumab vedotin may shrink the tumor by binding to tumor cells and delivering tumor-killing substances to them.

PRIMARY OBJECTIVES:

I. To characterize the clinical anti-tumor activity of CDX-011 (glembatumumab vedotin) as a single-agent in the treatment of patients with metastatic uveal melanoma.

SECONDARY OBJECTIVES:

I. Description of the clinical safety and benefit of CDX-011 (glembatumumab vedotin) and pharmacodynamics changes in glycoprotein NMB (glycoprotein \[transmembrane\] NMB) (GPNMB) expression.

TERTIARY OBJECTIVES:

I. Characterization of the anti-tumor immunophenotype of patients receiving treatment.

II. Post hoc, correlation of rash with clinical benefit, or lack of rash with lack of benefit, will also be explored.

OUTLINE:

Patients receive glembatumumab vedotin intravenously (IV) over 90 minutes every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Glembatumumab Vedotin in Treating Patients With Metastatic or Locally Recurrent Uveal Melanoma

A Phase 2 Study of CDX-011 (Glembatumumab Vedotin) for Metastatic Uveal Melanoma

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI and/or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (PD); PD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions

Target protein expression change from baseline to after 1 cycle of treatment.

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Toxicity will be reported by type, frequency, and severity. Only adverse events toxicity with grade 3-4 severity.

Overall survival as measured from time of enrollment to time of death due to any cause.

National Cancer Institute (NCI)

Patients receive glembatumumab vedotin IV over 90 minutes every 3 weeks in the absence of disease progression or unacceptable toxicity.

Glembatumumab Vedotin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Treatment (Glembatumumab Vedotin)

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Sapna Pradyuman Patel,MD/ Melanoma Medical Oncology

Partial Response

Stable Disease

Disease Progression

Unknown

participants who entered study and received treatment

Overall Response Rate Using Response Evaluation Criteria in Solid Tumors Version 1.1

Of 32 enrolled participants, 26 had baseline tissue available and 24 had Day 21 tissue available leaving only 22 evaluable for the secondary outcome measure: change in tumor expression from baseline to Day 21. In other words, only 22 participants had tumor collected for both baseline and Day 21 GPNMB expression.

The Number of Participants With Change in Glycoprotein NMB Expression on Tumor Tissue Via Immunohistochemistry

37 participants signed consent 1 participant withdrew consent for survival follow up

Progression-free Survival

Neutropenia

Thrombocytopenia

Diarrhea

Constipation

Vomiting

Rash, maculopapular

Pruritus

Number of Participants With Grade 3-4 Adverse Events According to the National Cancer Institute Common Toxicity Criteria Version 4.0

Overall Survival

Overall Study

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

glembatumumab vedotin

Celldex endeavors to make investigational products available to patients with life-threatening diseases who have exhausted other treatment options and where there is a reasonable expectation of benefit over risk. Requests for expanded access to glembatumumab vedotin in patients with gpNMB expressing triple negative breast cancer will be considered.

Individual Patient Expanded Access-Glembatumumab Vedotin

Celldex Therapeutics

Osteosarcoma

Disease Attributes

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Sarcoma

Soft Tissue Sarcoma

Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Lisa M Kopp

This phase II trial studies how well glembatumumab vedotin works in treating patients with osteosarcoma that has come back (recurrent) or does not respond to treatment (refractory). Monoclonal antibodies, such as glembatumumab vedotin, may find tumor cells and help kill them.

PRIMARY OBJECTIVES:

I. To estimate whether CDX-011 (glembatumumab vedotin) therapy either increases the disease control rate at 4 months in patients with recurrent measurable osteosarcoma as compared to an historical Children's Oncology Group (COG) experience or produces an objective response rate in patients without previous eribulin (eribulin mesylate) treatment.

SECONDARY OBJECTIVES:

I. To assess the feasibility and toxicity profile of CDX-011 in patients with recurrent osteosarcoma.

II. To describe the pharmacokinetics of CDX-011 in adolescents and young adults with recurrent osteosarcoma enrolled at COG sites and COG phase I consortium sites only.

III. To determine if there is a relationship between tumor GPNMB expression by immunohistochemistry (IHC) and response to CDX-011 therapy.

IV. To estimate, in the cohort of patients previously treated with eribulin, the proportion who will experience disease progression during the first 4 months of CDX-011 therapy and the proportion of patients who experience a Response Evaluation Criteria in Solid Tumors (RECIST)-defined complete or partial response.

OUTLINE:

Patients receive glembatumumab vedotin intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Glembatumumab Vedotin in Treating Patients With Recurrent or Refractory Osteosarcoma

A Phase 2 Study of GPNMB-Targeted Antibody-Drug Conjugate, CDX-011 (Glembatumumab Vedotin, CR011-vcMMAE; NSC# 763737), in Recurrent or Refractory Osteosarcoma

The number of patients who do not experience disease progression or death in the six cycles following enrollment on AOST1521

The number of cycles aggregated across all patients where CTC Version 4 grade 3 or higher.

Total antibody and antibody-drug conjugate half-life are estimated from the sampling time points: Before first dose (Baseline), end of infusion, at 1, 2, 4, and 24 hours post infusion

Total antibody and antibody-drug conjugate clearance are estimated from the sampling time points: Before first dose (Baseline), end of infusion, at 1, 2, 4, and 24 hours post infusion

Total antibody and antibody-drug conjugate areas under the curve are estimated from the sampling time points: Before first dose (Baseline), end of infusion, at 1, 2, 4, and 24 hours post infusion

GPNMB expression by IHC of 0+ to 3+ staining strength as assessed on archived tumor specimens. 0 being no GPNMB expression and 3 indicating strong GPNMB expression.

The number of patients who experience a complete or partial response according the RECIST criteria for target lesions complete response (CR) disappearance of all lesions; partial response (PR ) \>= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR+PR.

Adverse event reporting is collected routinely using case report forms. SAE field contains NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs. Ineligible patients are excluded from reporting of adverse events.

Patients receive glembatumumab vedotin IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

Glembatumumab Vedotin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Canada

Results Reporting Coordinator

Disease Control Success

Incidence of Abdominal Pain

Incidence of acneiform rash

Incidence of Anaphylaxis

Incidence of Anemia

Incidence of Anorexia

Incidence of Back Pain

Incidence of Constipation

Incidence of Febrile Neutropenia

Incidence of Headache

Incidence of Hypertension

Incidence of Hypocalcemia

Incidence of Hypokalemia

Incidence of Hypophosphatemia

Incidence of Hypotension

Incidence of Leukopenia

Incidence of Lymphopenia

Incidence of Mucocitis

Incidence of Myalgia

Incidence of Nausea

Incidence of Neutropenia

Incidence of Pain

Incidence of Pneumothorax

Incidence of Thrombocytopenia

22 patients were treated on protocol therapy. Sixty-one (61) cycles were reported for the analysis of toxicity.

Toxicity Associated With Chemotherapy

Total antibody half-life

Antibody-Drug Conjugate half-life

Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Half-life

Total antibody clearance

Antibody-Drug Conjugate clearance

Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Clearance

Total antibody area under the curve

Antibody-Drug Conjugate area under the curve

Pharmacokinetics of Glembatumumab Vedotin: Total Antibody and Antibody-drug Conjugate Areas Under the Curve

0+ staining strength

1+ staining strength

2+ staining strength

3+ staining strength

Analysis was successfully completed for 19 patients

Number of Participants With Glycoprotein NMB (GPNMB) Expression Stratified by Immunohistochemistry (IHC) Staining Strength

RECIST Response

Pembrolizumab

Immunomodulating Agents

Nivolumab

Immune Checkpoint Inhibitors

glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle.

glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Varlilumab administered as an intravenous infusion on Day 1 of cycles 1, 2, 4, 6, 8 and 10.

glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Nivolumab OR pembrolizumab administered according to institutional standard of care.

glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. CDX-301 is injected once a day for five days before cycles 1 and 2.

glembatumumab vedotin and varlilumab

glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab)

glembatumumab vedotin and CDX-301

This study will examine the effectiveness and safety of glembatumumab vedotin as monotherapy or in combination with immunotherapies in patients with advanced melanoma.

Glembatumumab vedotin consists of an antibody attached to a drug, monomethyl auristatin E (MMAE), that can kill cancer cells. The fully human antibody is designed to deliver the drug to cancer cells by attaching to a protein called glycoprotein NMB (gpNMB) that is expressed on the cancer cell. The MMAE is then released inside of the cell, where it interferes with cell growth and can lead to cell death of the targeted cell, as well as neighboring cells. Varlilumab is a fully human antibody that binds to CD27. This antibody allows the body's immune system to work against cancer cells. Nivolumab is a fully human antibody and pembrolizumab is a humanized antibody. Both bind to PD-1. CDX-301 is a fully human protein that helps boost production of certain white blood cells. This protein allows the body's immune system to work against tumor cells.

Eligible patients who enroll in the study will receive treatment with one of the following: glembatumumab vedotin, glembatumumab vedotin and varlilumab, glembatumumab vedotin and CDX-301 or glembatumumab vedotin and either nivolumab OR pembrolizumab.

All patients enrolled in the study will be closely monitored to determine if their cancer is responding to treatment and for any side effects that may occur.

A Study of Glembatumumab Vedotin as Monotherapy or in Combination With Immunotherapies in Patients With Advanced Melanoma

A Phase 2 Study of Glembatumumab Vedotin, an Anti-gpNMB Antibody-drug Conjugate, as Monotherapy or in Combination With Immunotherapies in Patients With Advanced Melanoma

ORR is defined as the percentage of patients who achieved best overall response of complete or partial response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST version 1.1), Complete Response (CR) = disappearance of all target lesions and non-target lesions, Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions with no progression in non-target lesions and no new lesions. ORR was the primary outcome for Cohorts 1-3 and a secondary outcome for Cohort 4.

The percentage of patients experiencing one or more adverse events.

DOR is the number of months from the time criteria are first met for either CR or PR, until the first date that PD is objectively documented per RECIST 1.1.

PFS is defined as the time from randomization to the earlier of disease progression or death due to any cause. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or progression in a non-target lesion, or the appearance of new lesions.

Overall Survival (OS) is defined as the number of months from randomization to the date of death due to any cause.

To investigate if the anti-cancer activity of glembatumumab vedotin as monotherapy or in combination with immunotherapies in advanced melanoma is dependent upon the degree of gpNMB expression in tumor tissue.

The percentage of patients experiencing one or more AEs will be summarized by relationship to study drug and severity.

glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle.

glembatumumab vedotin

glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Varlilumab administered as an intravenous infusion on Day 1 of cycles 1, 2, 4, 6, 8 and 10.

glembatumumab vedotin and varlilumab

Glembatumumab Vedotin and Varlilumab

glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. Nivolumab OR pembrolizumab administered according to institutional standard of care.

glembatumumab vedotin and PD-1 targeted checkpoint inhibitor (nivolumab OR pembrolizumab)

Glembatumumab Vedotin and PD-1 Targeted Checkpoint Inhibitor

glembatumumab vedotin administered as an intravenous infusion on Day 1 of each 21 day cycle. CDX-301 is injected once a day for five days before cycles 1 and 2.

glembatumumab vedotin and CDX-301

Glembatumumab Vedotin and CDX-301

Total

Age, Categorical

White

Black or African American

Asian

Other

Race/Ethnicity, Customized

Study was discontinued early, leading to small number of subjects analyzed in Cohort 4 and minimal patient follow up in Cohorts 3 and 4.

Head of Regulatory Affairs

Response evaluable (at least one dose and a post treatment disease assessment)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Glembatumumab Vedotin in Treating Patients With Metastatic or Locally Recurrent Uveal Melanoma	NCT02363283	Recurrent Uveal... Stage IV Uveal ...	Glembatumumab V... Laboratory Biom... Pharmacological...	18 Years -	National Cancer Institute (NCI)
Individual Patient Expanded Access-Glembatumumab Vedotin	NCT03067935	Metastatic gpNM...	glembatumumab v...	18 Years -	Celldex Therapeutics
Glembatumumab Vedotin in Treating Patients With Recurrent or Refractory Osteosarcoma	NCT02487979	Recurrent Osteo...	Glembatumumab V... Laboratory Biom... Pharmacological...	12 Years - 49 Years	National Cancer Institute (NCI)
A Study of Glembatumumab Vedotin as Monotherapy or in Combination With Immunotherapies in Patients With Advanced Melanoma	NCT02302339	Melanoma	glembatumumab v... glembatumumab v... glembatumumab v... glembatumumab v...	18 Years -	Celldex Therapeutics
Glembatumumab Vedotin in Treating Patients With Metastatic or Locally Recurrent Uveal Melanoma	NCT02363283	Recurrent Uveal... Stage IV Uveal ...	Glembatumumab V... Laboratory Biom... Pharmacological...	18 Years -	National Cancer Institute (NCI)
A Study of Glembatumumab Vedotin as Monotherapy or in Combination With Immunotherapies in Patients With Advanced Melanoma	NCT02302339	Melanoma	glembatumumab v... glembatumumab v... glembatumumab v... glembatumumab v...	18 Years -	Celldex Therapeutics
Study of Glembatumumab Vedotin in gpNMB-Expressing, Advanced or Metastatic SCC of the Lung	NCT02713828	Squamous Cell C...	Phase I: Glemba... Phase II: Glemb...	18 Years -	PrECOG, LLC.
Pilot Study of Glembatumumab Vedotin Following Doxorubicin and Cytoxan as Neo-adjuvant Therapy in Gp-NMB-expressing High Risk Triple Negative Breast Cancer	NCT03473691	Triple Negative...	Glembatumumab V...	18 Years -	University of Virginia

Spots Global Cancer Trial Database for glembatumumab vedotin