A Phase III Randomized Trial Comparing Physician/Patient Choice of Either High Dose Interferon or Ipilimumab to MK-3475 (Pembrolizumab) in Patients With High Risk Resected Melanoma

Plain English Summary

Physician/Patient Choice of Either High-Dose Recombinant Interferon Alfa-2B or Ipilimumab, Versus Pembrolizumab in Treating Patients With Stage III-IV High Risk Melanoma That Has Been Removed by Surgery is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8, Metastatic Cutaneous Melanoma, Metastatic Mucosal Melanoma, Metastatic Non-Cutaneous Melanoma, Non-Cutaneous Melanoma, Recurrent Cutaneous Melanoma, Recurrent Mucosal Melanoma, Recurrent Non-Cutaneous Melanoma. Tests different treatments for high-risk melanoma, comparing interferon, ipilimumab, and pembrolizumab. For patients with stage III-IV melanoma who have had surgery but are at risk of recurrence or spread. Participation involves regular check-ups, blood tests, and imaging scans. Alternatives include other immunotherapy drugs or standard care. The trial aims to enroll 1301 participants.

Official Summary

This randomized phase III trial studies how well pembrolizumab works compared with the current standard of care, physician/patient choice of either high-dose recombinant interferon alfa-2B or ipilimumab, in treating patients with stage III-IV melanoma that has been removed by surgery but is likely to come back or spread. High-dose recombinant interferon alfa-2B may help shrink or slow the growth of melanoma. Immunotherapy with monoclonal antibodies, such as ipilimumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether pembrolizumab is more effective than the current standard of care in treating patients with melanoma.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if you have stage III-IV melanoma that has been surgically removed. Not eligible if you have brain metastases, melanoma of ocular origin, or a history of brain metastases. Must be at least 18 years old. Good overall health with no severe organ issues. This trial is studying Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8, Metastatic Cutaneous Melanoma, Metastatic Mucosal Melanoma, Metastatic Non-Cutaneous Melanoma, Non-Cutaneous Melanoma, Recurrent Cutaneous Melanoma, Recurrent Mucosal Melanoma, Recurrent Non-Cutaneous Melanoma, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures survival, helping patients understand the effectiveness of different treatments. The specific primary outcome measures are: Overall Survival (OS) (5 years after last randomization). 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 fills a gap by comparing multiple treatment options for high-risk melanoma, potentially offering better outcomes. 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 Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8, Metastatic Cutaneous Melanoma, Metastatic Mucosal Melanoma, Metastatic Non-Cutaneous Melanoma, Non-Cutaneous Melanoma, Recurrent Cutaneous Melanoma, Recurrent Mucosal Melanoma, Recurrent Non-Cutaneous Melanoma, where improved treatment options are needed.

Investor Insight

Significant market size with a competitive landscape; approval probability is high given the unmet need in melanoma treatment. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 1301 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. 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: DOUBLE
• Enrollment: 1,301 participants

Interventions

• PROCEDURE: Biospecimen Collection — Undergo blood sample collection
• PROCEDURE: Computed Tomography — Undergo CT scan
• BIOLOGICAL: Ipilimumab — Given IV
• PROCEDURE: Magnetic Resonance Imaging — Undergo MRI
• BIOLOGICAL: Pembrolizumab — Given IV

Primary Outcomes

• Overall Survival (OS) (5 years after last randomization)

Secondary Outcomes

• Relapse-free Survival (RFS) (5 years after last randomization)
• Overall Survival (OS) in Participants Who Are PD-L1 Positive (94 months; from study start November 10, 2015 to September 15, 2023)
• Relapse-free Survival (RFS) in Participants Who Are PD-L1 Positive (5 years after last randomization)
• Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs (Randomized patients will be followed until death or 94 months (from study start November 10, 2015 to September 15, 2023), whichever occurs first.)

Full Eligibility Criteria

Inclusion Criteria:

* STEP 1 REGISTRATION:
* Patients must have completely resected melanoma of cutaneous origin or of unknown primary in order to be eligible for this study; patients must be classified as stage IIIA (N2a), IIIB, IIIC, or stage IV melanoma; patients with non-ulcerated T1b N1a disease are not eligible; patients with melanoma of mucosal or other non-cutaneous origin are eligible; patients with melanoma of ocular origin are not eligible; patients with a history of brain metastases are ineligible
* Patients are eligible for this trial either at initial presentation of their melanoma or at the time of the first detected nodal, satellite/in-transit, distant metastases, or recurrent disease in prior lymphadenectomy basin or distant site; nodal, satellite/in-transit metastasis, distant metastases or disease in a prior complete lymphadenectomy basin must have been confirmed histologically by hematoxylin and eosin (H \& E) stained slides
* Patients with multiple regional nodal basin involvement are eligible; gross or microscopic extracapsular nodal extension is permitted
* Patients at initial presentation of melanoma must undergo an adequate wide excision of the primary lesion, if present; patients with previously diagnosed melanoma must have had all current disease resected with pathologically negative margins and must have no evidence of disease at the primary site or must undergo re-resection of the primary site; a full lymphadenectomy meeting the criteria outlined is required for all node-positive patients including those with positive sentinel nodes; patients with recurrent disease who have had a prior complete lymphadenectomy fulfill this requirement as long as all recurrent disease has been resected; for all patients, all disease must have been resected with negative pathological margins and no clinical, radiologic, or pathological evidence of any incompletely resected melanoma; patients must be registered within 98 days of the last surgery performed to render the patient free of disease
* Patients must have available and be willing to submit a minimum of five unstained slides from primary, lymph node, or metastatic site to determine PD-L1 expression; the tumor tissue must be adequate for PD-L1 testing (defined as \>= 100 tumor cells as confirmed by the treating institution's local pathologist); this must be documented by having a pathologist sign the S1404 Local Pathology Review form prior to step 1 registration; the specimens may come from an archived block but must be submitted within 20 days from cutting the slides
* Patients must be offered the opportunity to participate in specimen banking as outlined
* Patients must be willing to have blood draws for PK/ADA analysis as outlined, should the patient be randomized to the MK-3475 arm
* Patients may have received prior radiation therapy, including after the surgical resection; all adverse events associated with prior surgery and radiation therapy must have resolved to =\< grade 1 prior to registration
* Patients must not have received neoadjuvant treatment for their melanoma; patients must not have had prior immunotherapy including, but not limited to ipilimumab, interferon alfa-2b, high dose IL-2, pegylated (PEG)-IFN, anti-PD-1, anti-PD-L1 intra-tumoral, or vaccine therapies; patients must not be planning to receive any of the prohibited therapies during the screening or treatment phases of the study
* Patients must not be planning to receive concomitant other biologic therapy, radiation therapy, hormonal therapy, other chemotherapy, surgery or other therapy after step 2 registration
* All patients must have disease-free status documented by a complete physical examination and imaging studies within 42 days prior to registration; imaging studies must include a total body positron emission tomography (PET)-computed tomography (CT) scan that is of diagnostic quality (with or without brain) or a CT of the chest, abdomen and pelvis; for patients with melanoma arising from the head and neck, dedicated neck imaging (CT with IV contrast or PET-CT through the region) is required; if the patient has had unknown primary with disease in the axilla, neck imaging is required to assure region is clear of cancer; CT imaging should be done with intravenous contrast if there are no contraindications for it; any other clinically-indicated imaging studies if performed (e.g. bone scan) must show no evidence of disease
* All patients must have a CT or magnetic resonance imaging (MRI) of the brain within 90 days prior to registration; the brain CT or MRI should be performed with intravenous contrast (unless contraindicated)
* Absolute neutrophil count (ANC) \>= 1,500 microliter (mcL) (within 42 days prior to registration)
* Platelets \>= 100,000 mcL (within 42 days prior to registration)
* Hemoglobin \>= 10 g/dL (within 42 days prior to registration)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN) (except Gilbert's syndrome, who must have

Trial Locations

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• Cancer Center at Saint Joseph's, Phoenix, Arizona, United States
• Virginia G Piper Cancer Care-Del Camino, Scottsdale, Arizona, United States
• Banner University Medical Center - Tucson, Tucson, Arizona, United States
• University of Arizona Cancer Center-North Campus, Tucson, Arizona, United States
• University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
• Highlands Oncology Group - Rogers, Rogers, Arkansas, United States
• Kaiser Permanente-Anaheim, Anaheim, California, United States
• Sutter Auburn Faith Hospital, Auburn, California, United States
• Kaiser Permanente-Baldwin Park, Baldwin Park, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Stage III-IV melanoma, metastatic melanoma, recurrent melanoma, cutaneous melanoma, mucosal melanoma, non-cutaneous melanoma.

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