Ivonescimab Plus Chemo Boosts OS in Pretreated EGFR+ NSCLC

Treatment with the combination of ivonescimab, pemetrexed, and carboplatin led to a statistically significant and clinically meaningful improvement in overall survival (OS) compared with placebo plus chemotherapy in patients with previously treated, locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR mutations, according to data from the final analysis of the phase 3 HARMONi-A trial (NCT05184712).1,2

“As the first phase 3 final analysis for ivonescimab, these results not only reinforce its breakthrough value in progression-free survival [PFS], but also highlight its ability to deliver significant OS improvement, a key end point in global oncology drug development,” according to a news release issued by Akeso Inc, the drug's developer and manufacturer.1

Previously reported data from the double-blind, placebo controlled study showed that at a median follow-up of 7.89 months, patients treated with ivonescimab plus chemotherapy (n = 161) experienced a median PFS of 7.1 months (95% CI, 5.9-8.7) compared with 4.8 months (95% CI, 4.2-5.6) for those given placebo plus chemotherapy (HR, 0.46; 95% CI, 0.34-0.62; P < .001).3

The PFS benefit was consistent across the majority of subgroups, including in patients whose disease progressed following treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI; HR, 0.48; 95% CI, 0.35-0.66) and those with brain metastases (HR, 0.40; 95% CI, 0.22-0.73).

Ivonescimab plus chemotherapy elicited an objective response rate (ORR) of 50.6% (95% CI, 42.6%-58.6%) compared with 35.4% (95% CI, 28.0%-43.3%) for placebo plus chemotherapy (P = .006).

HARMONi-A Overview

The multicenter trial enrolled patients aged 18 to 75 years with histologically or cytologically confirmed, locally advanced or metastatic nonsquamous NSCLC whose disease was inoperable and unamenable to chemoradiotherapy.2 Patients needed confirmation of an activating EGFR mutation, and disease progression following a prior EGFR TKI was also required.

Other key inclusion criteria included at least 1 measurable lesion per RECIST 1.1 criteria; an ECOG performance status of 0 or 1; a life expectancy of at least 3 months; and adequate organ function.

Patients with disease featuring any small-cell carcinoma components were not allowed to participate, along with patients who had squamous cell carcinoma as the primary component. Investigators also excluded patients harboring other mutations with available targeted therapies.

Patients were randomly assigned 1:1 to receive ivonescimab or placebo in combination with carboplatin and pemetrexed once every 3 weeks for 4 cycles. Patients then received ivonescimab plus pemetrexed or placebo plus pemetrexed as maintenance therapy once every 3 weeks for up to 2 years.

PFS served as the trial’s primary end point. Secondary end points included OS, ORR, disease control rate, duration of response, time to response, and safety.

Building on Data for Ivonescimab

In May 2025, Akeso also announced that in the phase 3 HARMONi trial (NCT06396065), ivonescimab plus platinum-doublet chemotherapy improved PFS vs placebo plus chemotherapy in patients with locally advanced or metastatic, nonsquamous, EGFR-mutated NSCLC who experienced disease progression following treatment with a third-generation EGFR TKI.4

In a news release, the company said that OS data were not yet mature.1

Data from the HARMONi will be presented at the 2025 World Conference on Lung Cancer in September.5

References

1. Akeso's 2025 interim results: commercial sales reach new all-time highs. News release. Akeso. August 26, 2025. Accessed August 26, 2025. https://www.prnewswire.com/news-releases/akesos-2025-interim-results-commercial-sales-reach-new-all-time-highs-302539063.html
2. Phase 3 clinical study of AK112 for NSCLC patients. ClinicalTrials.gov. Updated June 28, 2024. Accessed August 26, 2025. https://clinicaltrials.gov/study/NCT05184712
3. HARMONi-A Study Investigators, Fang W, Zhao Y, Luo Y, et al. Ivonescimab plus chemotherapy in non-small cell lung cancer with EGFR variant: a randomized clinical trial. JAMA. 2024;332(7):561-570. doi:10.1001/jama.2024.10613
4. Ivonescimab plus chemotherapy demonstrates statistically significant and clinically meaningful improvement in progression-free survival in patients with EGFR-mutant non-small cell lung cancer after EGFR TKI therapy in global study. News release. Summit Therapeutics. May 30, 2025. Accessed August 26, 2025. https://www.smmttx.com/wp-content/uploads/2025/05/2025_PR_0530-_-HARMONi-Data-_-FINAL.docx.pdf
5. Ivonescimab data from global phase III HARMONi study to be showcased at presidential symposium at WCLC 2025. News release. Summit Therapeutics. August 14, 2025. Accessed August 26, 2025. https://www.smmttx.com/wp-content/uploads/2025/08/2025_PR_0814-Announcement-of-WCLC-Attendance-_-FINAL.pdf