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Nivolumab

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Glembatumumab vedotin

Antibodies, Monoclonal

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Immunoconjugates

Immunologic Factors

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

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.

Celldex Therapeutics

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

glembatumumab vedotin

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

Sex: Female, Male

Ethnicity (NIH/OMB)

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)

Objective Response Rate (ORR)

Leukopenia

Abdominal pain

Constipation

Dyspepsia

Nausea

Stomatitis

Vomiting

Fatigue

Hepatic pain

Mucosal infection

Urinary tract infection

Alanine aminotransferase increased

Aspartate aminotransferase increased

Blood alkaline phosphatase increased

Neutrophil count decreased

Platelet count decreased

Weight decreased

Decreased appetite

Hyperglycemia

Hyperuricemia

Hypokalemia

Myalgia

Pain in extremity

Peripheral sensory neuropathy

Anxiety

Depression

Vaginal hemorrhage

Vulvovaginal pain

Epistaxis

Alopecia

Rash erythematous

Rash maculopapular

Skin discoloration

Hypertension

Adverse Events of the Combination of Glembatumumab Vedotin and CDX-301 (in Cohort 4).

Number of patients analyzed are the number of patients who achieved an objective response per Cohort. The response was observed at the last measurement without further follow up due to study closure.

Duration of Response (DOR)

Response evaluable (at least one dose and a post treatment disease assessment). The analysis was not completed for the glembatumumab + CDX-301 cohort because sufficient data were not collected to perform the analysis.

Progression-free Survival (PFS)

Response evaluable (at least one dose and a post treatment disease assessment). The analysis was not completed for the glembatumumab + CDX-301 cohort or the glembatumumab vedotin and PD-1 targeted checkpoint inhibitor cohort because sufficient data were not collected to perform the analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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
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

Spots Global Cancer Trial Database for targeted treatment for melanoma