A HER3-targeted drug beat chemo in EGFR lung cancer after targeted pills failed

People with EGFR lung cancer that grew on EGFR pills went a median 8.3 months without progression on ruzaltatug rezetecan, a HER3-targeted drug, vs. 5.4 months on chemotherapy, in a phase 3 trial in China published Oct. 26, 2026, in The Lancet. Serious side effects were similar, adding another option for this lung cancer.

Lung cancers driven by EGFR mutations are usually treated first with targeted pills. When the cancer grows despite them, chemotherapy has been the standard next step.

People on ruzaltatug rezetecan went a median of 8.3 months before their cancer grew, compared with 5.4 months on chemotherapy.

What is ruzaltatug rezetecan?

It’s an antibody-drug conjugate: an antibody that recognizes HER3 on cancer cells carries a dose of chemotherapy straight to them, like a guided missile. It’s a different drug from iza-bren, which targets EGFR and HER3 together.

What did the trial test?

At 62 sites in China, 498 adults aged 18 to 75 with advanced EGFR lung cancer that had progressed on EGFR pills were assigned by chance to ruzaltatug rezetecan or to standard platinum chemotherapy, both by IV every three weeks. Independent reviewers who didn’t know the treatment judged progression.

What did the study find about lung cancer?

	Ruzaltatug rezetecan	Chemotherapy
Median time without the cancer growing	8.3 months	5.4 months
Serious (grade 3+) side effects	41%	39%
Low white blood cell counts (neutrophils)	26%	19%
Anemia	6%	11%

The hazard ratio was 0.47. Few people stopped treatment because of side effects (1% in each group). This was an interim analysis, and survival data aren’t reported yet.

Why does this matter?

Resistance to EGFR pills is common, and for years chemotherapy was the main option left. Several antibody-drug conjugates are now being tested in this exact situation, each aimed at a different protein on the tumor. That competition is good news for patients, because it may soon give doctors more than one alternative to chemotherapy. It also means oncologists will need to learn which drug fits which patient, and in what order to use them, questions that future trials will have to answer.

How solid is this evidence?

It’s strong for what it measured. Mongevity rates it A on our A-to-E scale: a large randomized phase 3 trial with blinded review. Limits: it was open-label, done only in China, funded by the drug’s maker, Jiangsu Hengrui, and follow-up was short (median 7.7 months).

What does this mean for you?

If you or someone close to you has EGFR lung cancer that grew on targeted pills, new antibody-drug conjugates are worth asking the oncologist about, including clinical trials. Approval and access vary by country.

How do I explain this at dinner?

Some cancer medicines work like a delivery truck with an address label: they find a mark on the cancer cell and drop the medicine right there. This one looks for a mark called HER3. A good question for the table: why does it help to send something to the exact address?

In one sentence: an antibody-drug conjugate aimed at HER3 kept EGFR lung cancer in check longer than chemotherapy, with similar rates of serious side effects.