Recruiting
Phase 2

Ipilimumab & Nivolumab

Sponsor:

Emory University

Code:

NCT07155317

Conditions

Advanced Acral Melanoma

Advanced Cutaneous Melanoma

Advanced Mucosal Melanoma

Clinical Stage IV Cutaneous Melanoma AJCC v8

Metastatic Acral Melanoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biopsy Procedure

Biospecimen Collection

Computed Tomography

Ipilimumab

Magnetic Resonance Imaging

Study Details

Brief summary:

This phase II trial tests the safety and effectiveness of giving ipilimumab and nivolumab in the morning compared to other times of day in treating patients with melanoma that is stage IV or that cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the tumor and may interfere with the ability of tumor cells to grow and spread. While some patients have impressive outcomes with both of these drugs, over 40% of patients do not experience any clinical benefit. Studies have shown that the time of day that vaccines and other therapies are given have had an impact on response and survival. It is not known, however, whether time of day has an impact on response to immune checkpoint inhibitors, such as ipilimumab and nivolumab. Giving ipilimumab and nivolumab earlier in the day compared to later in the day may improve response to treatment and survival in patients with stage IV or unresectable melanoma.

Conditions

Advanced Acral Melanoma

Advanced Cutaneous Melanoma

Advanced Mucosal Melanoma

Clinical Stage IV Cutaneous Melanoma AJCC v8

Metastatic Acral Melanoma

Study ID

NCT07155317

Start date

Oct 29, 2025

Status verified date

Nov, 2025

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Pathologically confirmed American Joint Committee on Cancer (AJCC) 8th edition stage IV unresectable cutaneous, acral, or mucosal melanoma
  • No uveal melanoma
  • Patients with asymptomatic, non-hemorrhagic brain metastases < 2 cm are eligible
  • No prior immunotherapy within 1 year, (serine/threonine-protein kinase B-raf \[BRAF\]/mitogen-activated protein kinase \[MEK\] inhibitors allowed)
  • Eastern Cooperative Oncology Group (ECOG) 0-1
  • Age ≥ 18
  • Adequate organ function to receive ipilimumab/nivolumab

Exclusion Criteria:

  • Immunosuppression (> 10mg prednisone daily)
  • Active autoimmune disease that would preclude the administration of immunotherapy
  • Active leptomeningeal disease

Study Design

Enrollment

99 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm I (nivolumab, ipilimumab)

Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes at 0800-1100 on day 1 of each cycle. Cycles repeat every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance nivolumab for up to a total of 2 years. Patients wear an actigraphy device for 5-7 days at enrollment prior to first infusion and for up to 4 weeks then over 3 weeks starting with visit 4. Patients also undergo check swab and blood sample collection, CT or MRI and MRI or CT of brain throughout the study. Additionally, patients may optionally undergo tumor tissue biopsy throughout the study.

experimental: Arm II (nivolumab, ipilimumab)

Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes at 1100-1400 on day 1 of each cycle. Cycles repeat every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance nivolumab for up to a total of 2 years. Patients wear an actigraphy device for 5-7 days at enrollment prior to first infusion and for up to 4 weeks then over 3 weeks starting with visit 4. Patients also undergo check swab and blood sample collection, CT or MRI and MRI or CT of brain throughout the study. Additionally, patients may optionally undergo tumor tissue biopsy throughout the study.

active comparator: Arm III (nivolumab, ipilimumab)

Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes at 1400-1700 on day 1 of each cycle. Cycles repeat every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance nivolumab for up to a total of 2 years. Patients wear an actigraphy device for 5-7 days at enrollment prior to first infusion and for up to 4 weeks then over 3 weeks starting with visit 4. Patients also undergo check swab and blood sample collection, CT or MRI and MRI or CT of brain throughout the study. Additionally, patients may optionally undergo tumor tissue biopsy throughout the study.

Interventions

Biopsy Procedure

Undergo tumor tissue biopsy

Biospecimen Collection

Undergo check swab and blood sample collection

Computed Tomography

Undergo CT

Ipilimumab

Given IV

Magnetic Resonance Imaging

Undergo MRI

Medical Device Usage and Evaluation

Wear an actigraphy device

Nivolumab

Given IV

Questionnaire Administration

Ancillary studies

Primary outcome measure

  • Progression-Free Survival (PFS) A versus (vs.) C and B vs. C [ Time Frame: From randomization to progression or death, assessed up to 5 years ]

Central Contacts and Locations

Central contacts

Michael C. Lowe, MD, MA

404-778-0680mlowe3@emory.edu

Zachary Buchwald, MD, PhD

zachary.scott.buchwald@emory.edu

Locations

Emory University Hospital/Winship Cancer Institute

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Tiffaney Roundtree

tiffaney.laquinta.roundtree@emory.edu

Principal Investigator:

Michael C. Lowe, MD, MA

More Information

Sponsor

Emory University

Last update posted

Nov 12, 2025

Last verified

Nov, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Emory University on 2025-11-12.