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

NCT02302339 | Terminated Phase 2 Results

• 1 other identifier: CDX011-05
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 14

Brief Summary

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

Conditions

Melanoma

Keywords

Advanced melanoma; Unresectable melanoma; Metastatic melanoma; Targeted Treatment for melanoma; GPNMB; CDX-011; Glembatumumab vedotin; Antibody-drug-conjugate; Skin neoplasm; Varlilumab; CDX-1127

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  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.

  Every 6 to 9 weeks following treatment initiation until disease progression.

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

  The percentage of patients experiencing one or more adverse events.

  Up to 18 months following the screening visit

Secondary Outcomes (5)

• Duration of Response (DOR)

  From start date of partial or complete response (whichever is achieved first) to first date that recurrent of progressive disease is objectively documented, assessed up to 18 months.

• Progression-free Survival (PFS)

  Evaluated every 6 to 9 weeks following treatment initiation until progression.

• Overall Survival (OS)

  During treatment and every 3 months from end of treatment through death or end of study

• Correlation of Activity to gpNMB Expression

  Up to 18 months following the screening visit

• Adverse Events

  Following at least one dose of study treatment through 28 days after last dose of glembatumumab vedotin, or 70 calendar days after last administration of varlilumab, CDX-301 or PD-1 targeted checkpoint inhibitor (whichever occurs latest)

Study Arms (4)

Glembatumumab vedotin

EXPERIMENTAL

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

Drug: glembatumumab vedotin

Glembatumumab vedotin and varlilumab

EXPERIMENTAL

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.

Drug: glembatumumab vedotin and varlilumab

Glembatumumab vedotin and PD-1 targeted checkpoint inhibitor

EXPERIMENTAL

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.

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

Glembatumumab vedotin and CDX-301

EXPERIMENTAL

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.

Drug: glembatumumab vedotin and CDX-301

Interventions

glembatumumab vedotin DRUG

Also known as: Cohort 1

Glembatumumab vedotin

glembatumumab vedotin and varlilumab DRUG

Also known as: Cohort 2

Glembatumumab vedotin and varlilumab

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

Also known as: Cohort 3

Glembatumumab vedotin and PD-1 targeted checkpoint inhibitor

glembatumumab vedotin and CDX-301 DRUG

Also known as: Cohort 4

Glembatumumab vedotin and CDX-301

Eligibility Criteria

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

You may qualify if:

• Among other criteria, patients must meet all of the following conditions to be eligible for the study:
• Unresectable, histologically-confirmed advanced (Stage III or Stage IV) melanoma
• Disease progression during or after the last anticancer therapy received. For Cohort 3, progression must have occurred during the PD-1 targeted CPI (checkpoint inhibitor) treatment and the investigator has deemed it appropriate to continue treatment with the PD-1 targeted CPI beyond confirmed disease progression
• No more than one prior chemotherapy-containing regimen for advanced disease.
• Prior treatments received must include at least one CPI inhibitor (e.g., anti-CTLA-4, PD-1-, PD-L1-targeted immunotherapy) and for patients with a BRAF mutation at least one BRAF- or MEK-targeted therapy, unless patients are not candidates for, or refused, these therapies. For cohort 3, prior treatment received must include a PD-1 targeted CPI administered during the most recent disease progression and for patients with BRAF mutation at least one BRAF- or MEK-targeted therapy when appropriate
• The study site will submit paraffin-embedded tumor tissue obtained from the patient for gpNMB analysis. Patients may require a biopsy if recent tumor tissue is not available. Patients in cohort 2 and 3 must submit a recently obtained biopsy of the skin fold for gpNMB analysis. Patients in Cohort 4 will submit a tumor tissue sample while on study.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
• Adequate bone marrow, liver and renal function.

You may not qualify if:

• Among other criteria, patients who meet any of the following conditions are NOT eligible for the study:
• Previously received glembatumumab vedotin (CR011-vcMMAE, CDX-011) or other MMAE-containing agents
• Treatment with the following therapies before the planned start of study treatment:
• BRAF or MEK inhibitors within 2 weeks
• Monoclonal based therapies within 4 weeks except for the PD-1 targeted checkpoint inhibitor in cohort 3
• Immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) within 2 weeks
• Chemotherapy within 21 days or at least 5 half-lives (whichever is longer)
• Investigational therapy within 2 weeks (or at least 5 half-lives, whichever is longer)
• Patients with ocular melanoma
• Neuropathy that is moderate (Grade 2) or worse.
• Cancer that has spread to the brain or spine will be discussed with the study sponsor and may exclude patients from the trial.
• History of another cancer except:
• Patients with adequately treated and cured non-melanoma skin cancer or in situ cancer
• Patients with any other cancer from which the patient has been disease-free for ≥ 3 years
• Significant cardiovascular disease

Sponsors & Collaborators

• Celldex Therapeutics: lead

Study Sites (14)

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

Northern California Melanoma Center/St. Mary's Medical Center

San Francisco, California, 94117, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33916, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

Florida Cancer Specialists

West Palm Beach, Florida, 33407, United States

Location

Northside Hospital Cancer Institute

Atlanta, Georgia, 30341, United States

Location

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

New York University School of Medicine

New York, New York, 10016, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Baylor Research Institute-Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

glembatumumab vedotin; varlilumab; KPNA1 protein, human; Nivolumab; pembrolizumab

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

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

Results Point of Contact

• Title: Head of Regulatory Affairs
• Organization: Celldex Therapeutics

info@celldex.com

844-723-9363

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2014
• First Posted: November 27, 2014
• Study Start: November 1, 2014
• Primary Completion: June 14, 2018
• Study Completion: October 3, 2018
• Last Updated: September 6, 2019
• Results First Posted: September 6, 2019

Record last verified: 2019-08

Locations

US (14)