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

• Status: Terminated
• Trial end date: 2018-10-03
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Celldex Therapeutics
• Treatments: Antibodies, Monoclonal; Glembatumumab vedotin; Nivolumab; Pembrolizumab

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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:

1. BRAF or MEK inhibitors within 2 weeks

2. Monoclonal based therapies within 4 weeks except for the PD-1 targeted checkpoint inhibitor in cohort 3

3. Immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) within 2 weeks

4. Chemotherapy within 21 days or at least 5 half-lives (whichever is longer)

5. 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:

1. Patients with adequately treated and cured non-melanoma skin cancer or in situ cancer

2. Patients with any other cancer from which the patient has been disease-free for ≥ 3 years

• Significant cardiovascular disease

• Previously received varlilumab or any other anti-CD27 mAb (Cohort 2 only)

• Active systemic infection requiring treatment

• Treatment with immunosuppressive medications within 4 weeks or corticosteroids within two weeks

• Patients with interstitial lung disease (Cohort 3 only)

• Patients with active diverticulitis (Cohort 3 only)

• Any non-study vaccination within 4 weeks, or influenza vaccine within 2 weeks, prior to CDX-301 dosing (Cohort 4 only)