Plain language summary: comparing ivonescimab plus chemotherapy with placebo plus chemotherapy in people with advanced EGFR-mutated non–small cell lung cancer (NSCLC) whose disease worsened on EGFR-TKI treatment in the HARMONi study

Plain Language SummaryWhat is this summary about?HARMONi is a study of a new treatment for people with advanced or metastatic non–small cell lung cancer (NSCLC) with an activating mutation in the epidermal growth factor receptor (EGFR) gene. The study included participants in Asia, Europe, and North America whose cancer had gotten worse after treatment with an EGFR tyrosine kinase inhibitor (EGFR-TKI).Ivonescimab is a new type of cancer treatment that helps the immune system recognize and attack tumor cells. It also blocks the formation of new blood vessels that tumors need to grow. HARMONi compared ivonescimab plus chemotherapy with placebo plus chemotherapy.What were the results?Participants who were given ivonescimab plus chemotherapy lived longer without their cancer getting worse or spreading (called progression-free survival). The median progression-free survival was 6.8 months with ivonescimab plus chemotherapy compared with 4.4 months with placebo plus chemotherapy. This difference was statistically significant. The median overall survival, or the amount of time participants lived after starting treatment, was longer with ivonescimab plus chemotherapy (median, 16.8 months) compared with placebo plus chemotherapy (median, 14.0 months); however, this difference was not statistically significant.Two hundred and seven of 218 participants (95%, or about 9 out of every 10) who were given ivonescimab plus chemotherapy and 203 of 218 participants (93%, or about 9 out of every 10) who were given placebo plus chemotherapy had side effects related to their treatment. Common side effects with ivonescimab plus chemotherapy included changes in blood cell levels, nausea, decreased appetite, vomiting, and changes in liver enzymes. Some participants in each treatment group had severe or serious side effects. Four participants who received ivonescimab plus chemotherapy and five who received placebo plus chemotherapy died from treatment-related side effects.What do the results mean?For participants whose advanced NSCLC had gotten worse after EGFR-TKI treatment, ivonescimab plus chemotherapy resulted in a reduced risk of cancer getting worse or spreading by nearly half, compared with placebo plus chemotherapy. Overall survival was longer with ivonescimab plus chemotherapy; however, the difference was not statistically significant. Side effects occurred in a similar proportion of participants in both treatment groups. Most side effects could be managed without significantly impacting the participants’ quality of life or requiring treatment discontinuation.Clinical trial number: NCT06396065