Aerosolized Sargramostim Added to Immunotherapy for the Treatment of Patients With Metastatic Melanoma to the Lung

NCT05717140 | Withdrawn Phase 1 DMC FDA Drug

• 3 other identifiers: MC210704NCI-2023-0010222-002362
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests the safety, best dose, and effectiveness of inhaled aerosolized sargramostim in combination with standard immunotherapy (nivolumab) for the treatment of patients with melanoma that has spread from where it first started (primary site) to the lung (metastatic to the lung). Sargramostim works to stimulate the immune system by prompting the bone marrow to produce more white blood cells. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. In this study, an aerosolized form of sargramostim is inhaled using a device called a nebulizer, which can deliver the drug directly to the lungs. Inhalation of aerosolized sargramostim in combination with nivolumab may be more effective at treating patients melanoma metastatic to the lung.

Conditions

Clinical Stage IV Cutaneous Melanoma AJCC v8; Metastatic Malignant Neoplasm in the Lung; Metastatic Melanoma; Recurrent Melanoma; Unresectable Melanoma

Outcome Measures

Primary Outcomes (4)

• Maximum tolerated dose (MTD)

  The MRD is the dose level where at most 1 of the 6 patients treated at that dose level develops a dose-limiting event during the first cycle of treatment.

  During the first cycle of treatment (each Cycle = 28 ±3 days)

• Incidence of adverse events

  Adverse events will be identified using Common Terminology Criteria for Adverse Events version 5.0. The maximum grade of each type of adverse event will be recorded for each patient. For each adverse event reported by dose level, the percentage of patients developing any degree of that adverse event as well as the percentage of patients developing a severe degree (grade 3 or higher) will be determined.

  Up to 30 days after last treatment

• Progression-free survival (PFS)

  PFS distribution will be estimated using the Kaplan-Meier method.

  Time from study entry to the documentation of disease progression, assessed up to 2 years after registration

• Overall survival (OS)

  OS distribution will be estimated using the Kaplan-Meier method.

  Time from study entry to death, assessed up to 2 years after registration

Study Arms (1)

Treatment (aerosolized sargramostim, nivolumab)

EXPERIMENTAL

Patients receive aerosolized sargramostim via inhalation using the Aerogen Solo nebulization device and receive nivolumab IV on study. Patients also undergo collection of blood samples on study and undergo CT or MRI at screening and on study.

Biological: Aerosol Sargramostim; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Medical Device Usage and Evaluation; Biological: Nivolumab

Interventions

Aerosol Sargramostim BIOLOGICAL

Given via inhalation with nebulizer

Also known as: Aerosol GM-CSF

Treatment (aerosolized sargramostim, nivolumab)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (aerosolized sargramostim, nivolumab)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (aerosolized sargramostim, nivolumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Treatment (aerosolized sargramostim, nivolumab)

Medical Device Usage and Evaluation OTHER

Use Aerogen Solo nebulization device

Treatment (aerosolized sargramostim, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Treatment (aerosolized sargramostim, nivolumab)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 as defined
• Confirmed diagnosis of unresectable stage IV metastatic melanoma involving the lungs (at least) that has progressed after at least ONE line of Food and Drug Administration (FDA) approved therapy (either immune checkpoint inhibitor or targeted therapy) OR relapse of melanoma following/during FDA-approved adjuvant or neo-adjuvant therapy
• Hemoglobin \>= 8.0 g/dL (obtained =\< 15 days prior to registration)
• Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 15 days prior to registration)
• Platelet count \>= 75,000/mm\^3 (obtained =\< 15 days prior to registration)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (obtained =\< 15 days prior to registration)
• Alanine aminotransferase (ALT) AND aspartate aminotransferase (AST) =\< 3.0 x ULN (obtained =\< 15 days prior to registration)
• Serum creatinine =\< 2.0 x ULN (obtained =\< 15 days prior to registration)
• Calculated creatinine clearance \>= 40 ml/min using the Cockcroft-Gault formula (obtained =\< 15 days prior to registration)
• Pulse oximetry at rest \> 90% without use of supplemental oxygen
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Negative pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only
• Persons able to become pregnant OR able to father a child must be willing to use an adequate method of contraception while on treatment and for 180 days (6 months) after last treatment dose on this study
• Provide written informed consent

You may not qualify if:

• Active pulmonary disease requiring ongoing medication
• NOTE: Stable chronic medication for asthma/chronic obstructive pulmonary disease (COPD) is allowed
• Metastatic uveal melanoma
• Any of the following because this study involves an investigational agent the genotoxic, mutagenic, and teratogenic effects of which on the developing fetus and newborn are unknown:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential who are unwilling to employ adequate contraception
• Persons expecting to conceive or father children during the study or within 180 days (6 months) after the last treatment on this study
• Active central nervous system (CNS) metastases not previously treated
• NOTE: Patients with history of previously treated CNS metastases, not demonstrating evidence of progression for at least 8 weeks will be allowed
• NOTE: Patients with leptomeningeal metastases are not eligible
• Any of the following prior therapies:
• Allogeneic hematopoietic stem cell transplantation (HSCT)
• Solid organ transplantation
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Melanoma

Interventions

Specimen Handling; Magnetic Resonance Spectroscopy; Nivolumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Svetomir N. Markovic, M.D., Ph.D.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2023
• First Posted: February 8, 2023
• Study Start: October 28, 2025
• Primary Completion: January 28, 2026
• Study Completion: January 28, 2026
• Last Updated: August 7, 2025

Record last verified: 2025-08

Locations

US (1)