Ivonescimab Plus Chemo Delays NSCLC Development

Amongst sufferers with EGFR-mutated non-small cell lung most cancers (NSCLC) who skilled illness development following a third-generation tyrosine kinase inhibitor, therapy with ivonescimab plus carboplatin/pemetrexed was related to vital and clinically significant progression-free survival (PFS) versus placebo plus carboplatin/pemetrexed, examine outcomes have proven.

Knowledge from the section 3 HARMONi trial have been offered on the Worldwide Affiliation for the Examine of Lung Most cancers 2025 World Convention on Lung Most cancers, and the findings revealed that at a median follow-up of twenty-two.3 months, the median PFS was 6.8 months and 4.4 months within the ivonescimab plus carboplatin/pemetrexed (172 sufferers) and the placebo plus carboplatin/pemetrexed (173 sufferers) arms, respectively. Particularly, at six and 12 months within the ivonescimab arm, the PFS charges have been 54.% and 25.4%, respectively; these charges have been 34.7% and eight.3% within the placebo arm.

“The efficacy of [ivonescimab] was constant throughout subgroups, with maybe extra profit [in patients] with mind metastases,” Dr. Jonathan Goldman, a professor of drugs within the Division of Hematology/Oncology, the director of Medical Trials in Thoracic Oncology, and the affiliate director of Early Drug Improvement on the College of California Los Angeles, stated in a presentation of the information.

What Was the Background and Design of the HARMONi Examine?

Topline outcomes from the HARMONi trial revealed that the examine met the PFS major finish level and confirmed a optimistic pattern within the different major finish level of total survival (OS) with ivonescimab plus carboplatin/pemetrexed in contrast with placebo plus carboplatin/pemetrexed in sufferers with EGFR-mutated NSCLC who skilled illness development after therapy with a third-generation TKI.

The double-blind, multicenter trial contains sufferers not less than 18 years of age with histologically or cytologically confirmed unresectable domestically superior or metastatic non-squamous NSCLC with an EGFR-sensitizing mutation.

Sufferers included on the examine are randomly evenly assigned to obtain both ivonescimab plus carboplatin/pemetrexed (219 sufferers) or placebo plus carboplatin/pemetrexed (219 sufferers). These included within the investigational arm are handled with 20 mg/kg of ivonescimab each three weeks plus carboplatin at space below the curve 5 each three weeks for 4 21-day cycles and pemetrexed at 500 mg/m² each three weeks. Sufferers included within the placebo arm have been handled with carboplatin and pemetrexed on the identical dosing ranges as these within the investigational arm.

What Had been the Further Efficacy and Security Findings From the HARMONi Examine?

At an total median follow-up of 29.7 months, the median OS was 16.8 months and 14 months within the ivonescimab and placebo arms, respectively. Moreover, the target response charge (ORR) was 45% within the ivonescimab arm in contrast with 34% within the placebo arm. The illness management charge (DCR) was 84% vs 73% within the respective arms. Notably, the median period of response (DOR) within the ivonescimab (98 sufferers) and placebo (75 sufferers) arms have been 7.6 months and 4.2 months, respectively.

Relating to security, any-grade treatment-related unwanted side effects have been noticed in 95% and 93.1% of sufferers from the ivonescimab and placebo arms, respectively. Within the ivonescimab arm, grade 3 (extreme) or higher unwanted side effects and critical unwanted side effects occurred in 50% and 28% of sufferers, respectively; these occurred in 42.2% and 15.1% of sufferers within the placebo arm. Therapy-related unwanted side effects that led to discontinuation of ivonescimab or placebo, respectively, have been noticed in 7.3% and 5% of sufferers. Furthermore, treatment-related unwanted side effects that led to dying have been reported in 1.8% and a couple of.3% of sufferers, respectively.

Within the ivonescimab arm, the commonest treatment-related unwanted side effects noticed included anemia (any grade, 49.1%; grade 3 or increased, 10.1%), decreased white blood cell rely (45%; 12.8%), decreased neutrophil rely (42.7%; 19.3%) and decreased platelet rely (32.6%; 12.4%). The most typical treatment-related unwanted side effects reported within the placebo arm included anemia (56.4%; 12.4%), decreased white blood cell rely (44%; 11%), decreased neutrophil rely (42.2%; 16.5%) and decreased platelet rely (28.0%; 6.4%).

Of word, grade 3 or increased immune-related unwanted side effects occurred in 9.6% and 6% of sufferers within the ivonescimab and placebo arms, respectively; grade 3 or increased VEGF-related treatment-related unwanted side effects occurred in 7.3% and three.2% of sufferers. Specifically, the commonest irAEs occurring in not less than 5 sufferers within the ivonescimab arm included hypothyroidism (any grade, 8.3%; grade 3 or increased, 0.5%), hyperthyroidism (any grade, 4.1%), elevated alanine aminotransferase ranges (2.8; 0.9%), and elevated aspartate aminotransferase ranges (any grade, 3.2%). Moreover, the commonest VEGF-related treatment-related unwanted side effects occurring within the ivonescimab arm included proteinuria (13.8%; 0.9%), hypertension (13.3%; 3.7%) and hemorrhage (10.6%; 0.9%).

References

1. Goldman JW, Passaro A, Laskin J, et al. Ivonescimab vs placebo plus chemo, section 3 in sufferers with EGFR+ NSCLC progressed with third gen EGFR-TKI therapy: HARMONi. Introduced at: Worldwide Affiliation for the Examine of Lung Most cancers 2025 World Convention on Lung Most cancers; September 6-9, 2025; Barcelona, Spain. Summary 4808.
2. Ivonescimab plus chemotherapy demonstrates statistically vital and clinically significant enchancment in progression-free survival in sufferers with EGFR-mutant non-small cell lung most cancers after EGFR TKI remedy in international examine. Information launch. Summit Therapeutics. Could 30, 2025. Accessed September 7, 2025. https://www.smmttx.com/wp-content/uploads/2025/05/2025_PR_0530-_-HARMONi-Knowledge-_-FINAL.docx.pdf
3. Part III examine of AK112 for NSCLC sufferers. ClincialTrials.gov. Up to date October 8, 2024. Accessed September 7, 2025. https://clinicaltrials.gov/examine/NCT06396065

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