Ruzaltatug rezetecan versus chemotherapy for EGFR-mutated advanced non-small-cell lung cancer progressing after EGFR tyrosine kinase inhibitor therapy (HERON-Lung01): interim analysis of a randomised, open-label, phase 3 trial in China.
Chong-Rui Xu, Yan Zhang, Guinan Lin et al.
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In 30 seconds
HERON-Lung01 was a randomised, open-label, phase 3 trial at 62 sites in China comparing the HER3-directed antibody-drug conjugate ruzaltatug rezetecan with platinum-pemetrexed chemotherapy in patients with EGFR-mutated advanced non-squamous NSCLC progressing during or after EGFR-TKI therapy. In the prespecified interim analysis, blinded independent review found longer progression-free survival with ruzaltatug rezetecan: median 8·3 months versus 5·4 months (hazard ratio 0·47 [95% CI 0·36–0·60]; one-sided p<0·0001). Grade 3 or worse treatment-related adverse events occurred in 41% and 39%, respectively.
Key findings
- Median BICR-assessed progression-free survival was 8·3 months with ruzaltatug rezetecan versus 5·4 months with chemotherapy (hazard ratio 0·47 [95% CI 0·36–0·60]).
- Grade 3 or worse treatment-related adverse events occurred in 101 (41%) of 248 patients receiving ruzaltatug rezetecan and 93 (39%) of 239 receiving chemotherapy.
- Treatment-related adverse events led to discontinuation in three (1%) patients in each group; one death in the ruzaltatug rezetecan group was considered possibly treatment related.
Why it matters
After progression on EGFR-TKI therapy, this trial reports a significant interim progression-free survival advantage for ruzaltatug rezetecan over platinum-pemetrexed chemotherapy, with similar overall rates of severe treatment-related adverse events. The findings add phase 3 comparative evidence for a HER3-directed antibody-drug conjugate in this treatment setting, while longer follow-up and the ongoing trial may further inform its role.
What to keep in mind
This is an interim analysis with median follow-up of 7·7 months; the trial is ongoing. It was conducted at sites in China, which may limit generalisability to other populations.