Randomized Phase II/III Study of Nivolumab Plus Ipilimumab Plus Sargramostim Versus Nivolumab Plus Ipilimumab in Patients With Unresectable Stage III or Stage IV Melanoma

Plain English Summary

A Phase II/III Trial of Nivolumab, Ipilimumab, and GM-CSF in Patients With Advanced Melanoma is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Stage III Cutaneous Melanoma AJCC v7, Stage IV Cutaneous Melanoma AJCC v6 and v7. Tests a combination of nivolumab, ipilimumab, and sargramostim to treat advanced melanoma. For patients with unresectable stage III or IV melanoma who are 18 years or older and have not had certain treatments recently. Participation involves regular check-ups, blood tests, and imaging scans. Patients receive IV infusions of nivolumab and ipilimumab, and may also receive sargramostim. Alternative treatments include other immunotherapies and targeted therapies. The trial aims to enroll 600 participants.

Official Summary

This phase II/III trial studies the side effects of nivolumab and ipilimumab when given together with or without sargramostim and to see how well they work in treating patients with stage III-IV melanoma that cannot be removed by surgery (unresectable) and that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Colony-stimulating factors, such as sargramostim, may increase the production of white blood cells. It is not yet known whether nivolumab and ipilimumab are more effective with or without sargramostim in treating patients with melanoma.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if 18 years or older, in good health, and have advanced melanoma. Not eligible if pregnant, have active brain metastases, or have had certain treatments recently. Age: 18 years or older. Health: Good overall health, no active brain metastases, and no recent treatments. This trial is studying Stage III Cutaneous Melanoma AJCC v7, Stage IV Cutaneous Melanoma AJCC v6 and v7, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures overall survival, which means it tracks how long patients live after starting the treatment. The specific primary outcome measures are: Overall survival (Time from randomization to death from any cause, assessed up to 5 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to fill a treatment gap by comparing the effectiveness of nivolumab, ipilimumab, and sargramostim versus nivolumab and ipilimumab alone in advanced melanoma patients. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Stage III Cutaneous Melanoma AJCC v7, Stage IV Cutaneous Melanoma AJCC v6 and v7, where improved treatment options are needed.

Investor Insight

The large market size and competitive landscape suggest a high approval probability for this trial. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 600 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor about your eligibility and the potential benefits and risks. Participation involves regular check-ups, blood tests, and imaging scans. You will receive IV infusions of nivolumab and ipilimumab, and may also receive sargramostim. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 600 participants

Interventions

• PROCEDURE: Biospecimen Collection — Undergo blood sample collection
• PROCEDURE: Computed Tomography — Undergo CT scan
• PROCEDURE: Echocardiography Test — Undergo ECHO
• BIOLOGICAL: Ipilimumab — Given IV
• PROCEDURE: Magnetic Resonance Elastography — Undergo MRI

Primary Outcomes

• Overall survival (Time from randomization to death from any cause, assessed up to 5 years)

Secondary Outcomes

• Progression free survival (Time from randomization to disease progression or death (whichever occurs first), assessed up to 5 years)
• Incidence of toxicities (Up to 90 days after the last study drug administration)
• Immune response (Up to 5 years)
• Clinical response (Up to 5 years)

Full Eligibility Criteria

Inclusion Criteria:

* All patients must be \>= 18 years of age
* Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1
* Patients must have known BRAF mutational status of tumor; wild-type (WT) or mutated, prior to randomization
* Patients must not be pregnant or breast-feeding due to use of cytotoxic immunotherapy and risk of teratogenic side effects; all patients of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy; a patient of childbearing potential is anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients must not conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of study registration and continuing (for patients of child bearing potential) for at least 5 months after the last dose of protocol treatment; patients of childbearing potential must also not donate eggs during this same time period
* Patients must have unresectable stage III or stage IV melanoma according to American Joint Committee on Cancer (AJCC) version (v)7; patients must have histological or cytological confirmation of melanoma that is metastatic or unresectable and clearly progressive
* Patients must have measurable disease per RECIST 1.1 criteria; all sites of disease must be evaluated within 4 weeks prior to randomization
* Patients may have had prior systemic therapy in the adjuvant setting (e.g. interferon, BRAF, or MEK agents). Patients may have had prior anti-CTLA-4 in the adjuvant setting, if at least one year from last dose of treatment has passed prior to beginning treatment. Patients may have had any prior anti-PD-1 or anti-PD-L1 agent in the adjuvant setting, if at least one year from last dose of treatment has passed prior to beginning treatment
* Patients may not have had any prior ipilimumab and/or anti-PD-1/PD-L1 agent in the metastatic setting
* Patients must have discontinued chemotherapy, immunotherapy or other investigational agents used in the adjuvant setting \>= 4 weeks prior to randomization and recovered from adverse events due to those agents; mitomycin and nitrosoureas must have been discontinued at least 6 weeks prior to entering the study; patients must have discontinued radiation therapy \>= 2 weeks prior to entering the study and recovered from any adverse events associated with treatment; prior surgery must be \>= 4 weeks from randomization and patients must be fully recovered from post-surgical complications
* Patients must not receive any other investigational agents while on study or within four weeks prior to randomization
* Patient must not have received any live vaccine within 30 days prior to randomization, while participating in the study, and for 4 weeks (28 days) after the last dose of protocol treatment; live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine; patients are permitted to receive inactivated vaccines and any non-live vaccines including those for the seasonal influenza and coronavirus disease 19 (COVID-19) (Note: intranasal influenza vaccines, such as Flu-Mist (registered trademark) are live attenuated vaccines and are not allowed); if possible, it is recommended to separate study drug administration from vaccine administration by about a week (primarily, in order to minimize an overlap of adverse events)
* Patients are ineligible if they have any currently active central nervous system (CNS) metastases; patients who have treated brain metastases (with either surgical resection or stereotactic radiosurgery) that have been stable on head magnetic resonance imaging (MRI) or contrast computed tomography (CT) scan for at least 4 weeks following treatment and within 4 weeks prior to randomization are eligible; patients must not have taken any steroids =\< 14 days prior to randomization for the purpose of managing their brain metastases; patients with only whole brain irradiation for treatment of CNS metastases will be ineligible
* Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast; patients with other malignancies are eligible if they have been continuously disease-free for \> 3 years prior to the time of randomization
* White blood count \>= 3,000/uL (obtained within 4 weeks prior to randomization)
* Absolute neutrophil count (ANC) \>= 1,500/uL (obtained within 4 weeks prior to randomization)
* Platelet count \>= 100,000/uL (obtained within 4 weeks prior to randomization)
* Hemoglobin 

Trial Locations

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• Kingman Regional Medical Center, Kingman, Arizona, United States
• CARTI Cancer Center, Little Rock, Arkansas, United States
• John L McClellan Memorial Veterans Hospital, Little Rock, Arkansas, United States
• Kaiser Permanente-Anaheim, Anaheim, California, United States
• Kaiser Permanente-Deer Valley Medical Center, Antioch, California, United States
• PCR Oncology, Arroyo Grande, California, United States
• Sutter Auburn Faith Hospital, Auburn, California, United States
• Sutter Cancer Centers Radiation Oncology Services-Auburn, Auburn, California, United States
• Kaiser Permanente-Baldwin Park, Baldwin Park, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Stage III Cutaneous Melanoma
• Stage IV Cutaneous Melanoma
• Advanced Melanoma
• Immunotherapy
• Targeted Therapy
• Brain Metastases
• Cancer Immunotherapy
• Cancer Clinical Trials
• Advanced Cancer Treatments
• Immunotherapy for Cancer

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