Who is this for?
This is for people with advanced liver cancer (hepatocellular carcinoma) that can’t be removed by surgery, who are starting their first drug treatment.
It builds on a big shift in liver-cancer care: moving away from single targeted pills toward immunotherapy. Our summary of the IMbrave150 trial covers one immunotherapy approach (an immunotherapy drug paired with an anti-blood-vessel drug); this trial tested a different one — two immunotherapy drugs together.
What kind of trial is this?
CheckMate 9DW was a global phase III randomized trial — the most rigorous kind — comparing the two-immunotherapy combination against a standard targeted pill (the doctor’s choice of lenvatinib or sorafenib) as a first treatment for advanced liver cancer.
Background: another way to use immunotherapy
Immunotherapy transformed liver-cancer treatment, but there is more than one way to deliver it. One approach pairs a single immunotherapy drug with an anti-blood-vessel drug (as in IMbrave150). Another combines two immunotherapy drugs, each releasing a different immune brake — a strategy that, in other cancers, can produce especially deep and long-lasting responses.
CheckMate 9DW tested whether this two-immunotherapy combination could beat the old standard pills in liver cancer.
The trial: what was tested and how
CheckMate 9DW enrolled 668 people with untreated, unresectable liver cancer. They were randomly assigned to one of two treatments:
- Nivolumab + ipilimumab (335 people): the two immunotherapy drugs together for four doses, then nivolumab alone as maintenance.
- Lenvatinib or sorafenib (333 people): a standard targeted pill chosen by the doctor.
The main measure was how long people lived (overall survival).
Results: what they found
Dual immunotherapy shrank the tumor far more often, produced longer-lasting responses, and helped people live longer overall — with an important caveat about the first few months.
Nivolumab + ipilimumab vs standard pills
A 21% lower risk of death overall (HR 0.79). The advantage grew over time: 38% were alive at 3 years, versus 24% — a durable, long-term benefit.
Nearly three times as many tumors shrank, and the responses lasted much longer (a median of about 30 months vs 13) — nearly half of responders were still in response at 3 years.
In the first few months, more deaths occurred in the immunotherapy group before its benefit emerged — because dual immunotherapy takes time to work, and some cancers progress before it does. After that, the survival curves clearly favored immunotherapy.
How does this compare with the other liver-cancer immunotherapy (IMbrave150)?
Both are first-line options and there’s no head-to-head trial. The two-immunotherapy combination here (nivolumab + ipilimumab) shrinks the tumor more often and can produce very durable responses, but carries more early risk and immune side effects. The atezolizumab + bevacizumab approach has a gentler start. The right choice depends on the person’s liver function, other health conditions, and how urgently the cancer needs controlling — a shared decision with the oncology team.
How does dual immunotherapy work?
The immune system has built-in “brakes” that cancers exploit to hide. Nivolumab releases one brake (PD-1) and ipilimumab releases another (CTLA-4); used together they let immune cells recognize and attack the cancer. Our kidney-cancer summary has a diagram showing exactly how these two brakes work.
What are the side effects?
Because immunotherapy unleashes the immune system, it can sometimes attack healthy organs — causing inflammation of the liver, bowel, skin, or hormone glands. In people whose liver is already compromised by cancer, liver inflammation needs careful watching. Overall, serious side effects were about as common as with the standard pills, but the type differs, and early recognition matters.
The bottom line
For advanced liver cancer, two immunotherapy drugs together (nivolumab + ipilimumab) helped people live longer than the standard targeted pills — shrinking the tumor nearly three times as often, producing long-lasting responses, and lifting 3-year survival from 24% to 38%. The trade-off is more risk in the first few months, before the immunotherapy takes hold. It gives people with liver cancer a second strong immunotherapy-based option alongside atezolizumab + bevacizumab.
What this could mean for you
- There’s more than one immunotherapy option. For advanced liver cancer, both a two-immunotherapy combination and an immunotherapy-plus-anti-blood-vessel combination are now first-line choices.
- Dual immunotherapy aims for durable responses — deeper, longer-lasting tumor shrinkage in those who respond.
- The early months carry more risk with this approach; close monitoring at the start is important.
- Liver function and other factors guide the choice between the available options — a decision to make with your team.
Questions & comments
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