Denosumab + PD-1 in Subjects With Stage III/ IV Melanoma

Recruiting at1 trial location

Overseen by Stergios Moschos, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: UNC Lineberger Comprehensive Cancer Center

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is a multicenter open-label, single-arm, phase II study designed to investigate the pharmacodynamic and antitumor effects of denosumab alone and in combination with an anti-Programmed death-1 or Programmed death ligand 1 (PD1) agent (pembrolizumab or nivolumab) in patients with unresectable Programmed death-1 or Programmed death ligand 1 (PD-1/PD-L1) inhibitor-naïve regional and distant metastatic melanoma (The American Joint Committee on Cancer (AJCC) stage III/IV). The pharmacodynamic and antitumor effects will be investigated by performing translational research on peripheral blood and tumor tissue collected before and during denosumab alone and in combination with anti-PD-1 treatment.

Research Team

Stergios Moschos, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

Inclusion Criteria

Albumin ≥ 2.5 mg/dL

Aspartate aminotransferase (AST) ≤ 2.5 × ULN OR < 5 × ULN for subjects with liver metastases

Alanine aminotransferase (ALT) ≤ 2.5 × ULN OR < 5 × ULN for subjects with liver metastases

Exclusion Criteria

You had cancer in the past, but there are some exceptions.

Treatment with any investigational drug, immunotherapy or chemotherapy within 28 days prior to study treatment.

Has active autoimmune disease that has required systemic treatment in the past 2 years.

Treatment Details

Interventions

• Denosumab (Monoclonal Antibodies)
• Nivolumab (Monoclonal Antibodies)
• Pembrolizumab (Monoclonal Antibodies)

Participant Groups

Group I: Single Arm: Denosumab+ PD-1 Inhibitor Experimental Treatment 3 Interventions

Subjects in this trial will be given denosumab every 4 weeks, starting on day 1 of study treatment. An additional loading dose of denosumab will be administered on day 8. Subjects who started Pembrolizumab (initiated 21 days after the first dose of denosumab is given) will continue to have it administered intravenously (IV) every 3 weeks. New subjects will receive Nivolumab administered intravenously (IV) every 4 weeks (initiated 21 days after the first dose of denosumab is given). Combination therapy will continue as long as subjects benefit from therapy for up to 1 year.

Denosumab is already approved in Canada, Japan for the following indications:

Approved in Canada as Prolia for:

• Treatment of osteoporosis in postmenopausal women at high risk for fracture
• Treatment to increase bone mass in men with osteoporosis at high risk for fracture

Approved in Japan as Prolia for:

• Treatment of osteoporosis in postmenopausal women
• Treatment of bone loss associated with hormone ablation therapy for prostate cancer

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Dr. Shelley Earp

UNC Lineberger Comprehensive Cancer Center

Chief Medical Officer since 2018

MD from Johns Hopkins Medical School

Dr. Robert L. Ferris

UNC Lineberger Comprehensive Cancer Center

Chief Executive Officer

PhD in Immunology and MD from Johns Hopkins Medical School; Bachelor's in Chemistry from UNC-Chapel Hill

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London