Every year, ASCO serves as a barometer for where oncology is headed, and melanoma always holds a special place on my radar. Having spent a large part of the past decade deeply involved in treating melanoma patients and working on multiple melanoma clinical trials, I naturally gravitate toward the melanoma sessions. This year’s oral abstracts in melanoma delivered some particularly intriguing updates that span the adjuvant, neoadjuvant, and metastatic spaces—including the always challenging CNS metastases population.
For this post, I want to highlight four key studies that stood out. The goal here is to summarize the data in a way that’s engaging and accessible—not just for oncologists—but also for healthcare professionals, industry colleagues, and anyone with an interest in how melanoma treatment continues to evolve.
1. EORTC 2139/MG Columbus-AD (Adjuvant Encorafenib/Binimetinib in Stage IIB/IIC Melanoma)
Presenter: Alexander Akkooi, et al.
This phase II randomized trial explored targeted therapy in patients with resected Stage IIB/C cutaneous melanoma harboring BRAF V600E/K mutations—a group already known for higher-than-average recurrence risk.
Historically, adjuvant PD-1 blockade (from trials like KEYNOTE-716 and CheckMate-76K) has been the go-to in this setting, offering around a 10% absolute improvement in relapse-free survival (RFS). But could BRAF/MEK inhibition (already standard in Stage III/IV BRAF-mutant melanoma) play a role here?
Key findings:
- Patients enrolled: ~110 (smaller than planned, due to slower accrual)
- Treatment arms: Encorafenib/Binimetinib for 1 year vs. placebo
- 1-year RFS: 86% for E+B vs. 72% for placebo
- Distant metastasis-free survival (DMFS): 92% vs. 82%, respectively
- Safety: Toxicities were in line with what we know from metastatic use—less pyrexia and photosensitivity than earlier-generation BRAF/MEK inhibitors.
While small and not practice-changing yet, this study represents the first randomized trial of adjuvant targeted therapy in Stage IIB/C melanoma, and the signal is encouraging enough to hope for a larger phase III study down the line. For now, adjuvant PD1 inhibitors is still the preferred option but perhaps for those with contraindications to immunotherapy and if ctdna positive… just forward thinking where I would consider this option?
2. Triple Therapy for Symptomatic BRAF-Mutant Brain Metastases
Presenter: Dr. Zeynep Eroglu, et al.
Let’s pivot to one of the most difficult melanoma populations we treat: symptomatic, BRAF-mutant brain metastases—especially those requiring steroids. Historically, outcomes here have been dismal, with limited efficacy from standard immunotherapy and challenges enrolling these patients on trials.
This Phase II trial compared upfront triplet therapy (Encorafenib + Binimetinib + Nivolumab) versus ipilimumab + nivolumab (Ipi/Nivo) in symptomatic BRAF-mutant brain metastases.
Key results:
- Patients enrolled: 60+ (tough population to accrue)
- 6-month intracranial PFS: 60% with triplet vs. 13% with Ipi/Nivo
- Overall intracranial PFS: 8.7 months (triplet) vs. 1.5 months (Ipi/Nivo)
- Intracranial response rate: 67% (triplet) vs. 14% (Ipi/Nivo)
- Overall survival (OS): Roughly 9 months (triplet) vs. 14 months (Ipi/Nivo)—though small numbers make this hard to interpret definitively.
My take: For symptomatic, steroid-dependent patients needing rapid control, this trial supports starting with triplet therapy. But for longer-term disease control and OS benefit, Ipi/Nivo likely remains the backbone, especially when patients can tolerate it. This study opens doors for sequencing or combination approaches—get control upfront, then layer in doublet immunotherapy after maximal triplet response for durability?
3. Neoadjuvant TLR9 Agonist + Anti-PD-1 in Stage III Melanoma
Presenter: Dr. Ahmad Tarhini, et al.
Moving to earlier-stage disease, this phase II neoadjuvant trial looked at Vidutolimod (a TLR9 agonist) plus pembrolizumab vs. pembrolizumab alone in patients with resectable, macroscopic Stage IIIB-D melanoma.
Vidutolimod works by activating dendritic cells and promoting interferon-alpha driven inflammation—essentially giving the immune system a strong kick right where the tumor lives.
Results:
- Pathologic response (major or complete): 81% with the combination vs. 68% with pembro alone
- 1-year event-free survival: 89% (combo) vs. 75% (pembro)
- Safety: Acceptable in both arms with no major surprises
Why this matters: This builds on growing evidence that neoadjuvant immunotherapy—especially when coupled with agents that modulate the tumor microenvironment—can deepen responses pre-surgery and potentially improve long-term outcomes. Use the patient’s own tumor like their own personalized vaccine to deliver robust immune response locally but more importantly systemically… cause the primary/regional tumors are coming out.
4. Final 5-Year Results from the DREAMseq Trial (Upfront Ipi/Nivo vs. Targeted Therapy in BRAF-Mutant Stage IV Melanoma)
Presenter: Dr. Michael Atkins, et al.
The long-awaited final OS data from DREAMseq is in—and it confirms what many of us have already adopted in practice: For treatment-naïve, BRAF-mutant Stage IV melanoma, double Ipi-Nivo immunotherapy comes first.
Key results:
- 5-year OS: 49% for Ipi/Nivo first vs. 35% for targeted therapy first
- 2-year PFS: 50% (Ipi/Nivo) vs. 22% (targeted first)
- 5-year PFS: 39% vs. 12%, respectively
- Durable responses and brain metastasis-free survival also favored the immunotherapy-first strategy.
This trial has shaped frontline decision-making for years, and now with 5-year data, it cements Ipi/Nivo first as the standard for most fit patients with BRAF-mutant metastatic melanoma.
Final Thoughts
These four studies capture where melanoma is heading: personalized, stage-specific strategies that blend the strengths of targeted therapy, immunotherapy, and novel immune modulators—whether it’s treating early-stage disease, preventing recurrence, or managing the most difficult CNS presentations.
For those in the oncology community, these results offer both validation of current practice and a glimpse of where the field might pivot next. And as always—credit to the investigators, patients, and research teams who made these studies possible.
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. He brings a wealth of expertise to the complex and challenging world of oncology.
Disclosures:
Dr. Thomas serves as a speaker for Bristol Myers Squibb (BMS), Merck, Ipsen, Natera, Immunocore, Pfizer, and SpringWorks. He also receives industry grants in support of numerous clinical trials.