Who is this trial for?
This trial was for adults with metastatic melanoma (skin cancer that had spread) whose tumors carried a BRAF V600 mutation, who had not yet been treated for their advanced disease.
People in the trial had:
- Unresectable or metastatic melanoma — melanoma that could not be removed by surgery, or had spread to other parts of the body.
- A BRAF V600 mutation, found in about 40–50% of melanomas, which opens the door to targeted therapy.
- No previous treatment for the advanced cancer.
What kind of trial is this?
This trial did not test a new drug — it tested the best strategy for using treatments we already have. Questions like this — about sequence, timing, and order — are exactly the “how we make decisions” questions that shape everyday care.
Background: why researchers asked this question
For BRAF-mutant melanoma, both immunotherapy and targeted therapy work — but they behave differently. Targeted therapy tends to bring fast relief, which is valuable for someone with a lot of cancer causing symptoms. Immunotherapy tends to work more slowly, but when it works it can last a very long time.
That left oncologists with a real dilemma: which should you start with? And is there a clever “sandwich” approach — a short burst of targeted therapy to shrink the cancer quickly, then a switch to immunotherapy for durable control? SECOMBIT tested all three strategies head to head.
The trial: what was tested and how
SECOMBIT enrolled 209 people and randomly assigned them to one of three sequences:
- Arm A — targeted first: encorafenib + binimetinib until the cancer progressed, then switch to ipilimumab + nivolumab.
- Arm B — immunotherapy first: ipilimumab + nivolumab until progression, then switch to encorafenib + binimetinib.
- Arm C — the “sandwich”: a short 8-week burst of encorafenib + binimetinib to shrink the cancer quickly, then switch to ipilimumab + nivolumab, with targeted therapy again later if needed.
The main measure was overall survival at 2 years. Importantly, this was a phase II trial designed to see whether each strategy cleared a survival bar — not to prove one arm beat the others head to head.
Results: what they found
Every sequence delivered strong survival — far better than what melanoma patients could expect a decade earlier. All three cleared the survival benchmark comfortably, and no arm ran into unexpected safety problems.
Overall survival by sequence
Starting with immunotherapy gave the highest 2-year survival, with the sandwich approach close behind.
The same pattern held at 3 years. Median survival was not reached in any arm — meaning more than half the people in every group were still alive when the study reported.
The take-home message is nuanced. All three strategies are reasonable, and there was no dramatic gap between them — but the numbers leaned toward starting with immunotherapy. A separate, larger U.S. trial called DREAMseq asked the same question and found the same direction: beginning with immunotherapy led to better survival than beginning with targeted therapy. Together, these trials shifted everyday practice toward immunotherapy first for most people.
So when might targeted therapy go first?
When someone has a large amount of fast-growing cancer causing symptoms, the speed of targeted therapy can be valuable — it often shrinks tumors within days to weeks, buying time and relief. The sandwich approach (Arm C) was designed for exactly this: a quick burst of targeted therapy to gain control, then a switch to immunotherapy for lasting benefit. The right choice depends on how much cancer there is, how fast it is moving, and the individual person.
The bottom line
For BRAF-mutant metastatic melanoma, all three ways of sequencing immunotherapy and targeted therapy gave strong long-term survival — but the results leaned toward starting with immunotherapy. Combined with the U.S. DREAMseq trial, which pointed the same way, this helped establish immunotherapy-first as the usual approach for most patients, while keeping a fast-acting targeted option for those who need quick control.
What this could mean for you
- Order matters, and it’s a real decision. Both treatments work; the sequence is chosen with your oncologist based on your situation.
- Immunotherapy first for many. When there’s time to let it work, starting with immunotherapy tends to give the best long-term odds.
- Targeted therapy for speed. If the cancer is bulky or moving fast, starting with (or briefly using) targeted therapy can bring quick relief before switching.
Related summaries: CheckMate 067 (ipilimumab + nivolumab) and RELATIVITY-047 — more on immunotherapy for advanced melanoma.
Questions & comments
Have a question about this trial? Ask below. Questions are read and answered by the site. We can’t give personal medical advice, but we’re glad to explain the research more clearly.