Topline Findings
- Positive Overall Survival (OS) Trend: Ivonescimab plus chemotherapy showed a favorable OS trend in EGFR-mutated NSCLC, with median OS of 16.8 months versus 14 months for placebo (HR 0.79; p=0.057), reinforced by longer-term follow-up.
- Clinically Meaningful Efficacy: The treatment demonstrated significant improvements in progression-free survival (median PFS 6.8 vs. 4.4 months; HR 0.52) and overall response rate (45% vs. 34%); however, benefits varied among Western and Asian patients, with Asian patients experiencing significantly longer PFS.
- Manageable Safety Profile: Ivonescimab plus chemotherapy was well-tolerated, with common treatment-related adverse events that included anemia and decreased blood cell counts, and fewer than 1% experiencing grade ≥3 hemorrhage events.
Results from the Phase III HARMONi trial (NCT06396065) showed that Summit Therapeutics’ ivonescimab demonstrated a positive overall survival (OS) trend in patients with EGFR-mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). The trial evaluated ivonescimab plus platinum-doublet chemotherapy versus placebo plus chemotherapy.1
How did Ivonescimab Perform in the HARMONi Trial Compared to Standard Chemotherapy Alone?
“The positive results from the HARMONi study underscore the global applicability of ivonescimab and demonstrates the potential benefit ivonescimab has to bring to patients around the world, including the United States,” said Robert W. Duggan, chairman, co-CEO, Summit Therapeutics, in a press release. “We appreciate that the US FDA worked together with us in order to continue this trial from the single-region into this multiregional setting for which we are sharing detailed results today, bringing ivonescimab closer to the forefront for patients in need globally.”
HARMONi Trial Design and Key Endpoints
- The randomized, double-blind, multi-center, HARMONi trial evaluated ivonescimab in approximately 420 patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who had progressed on third-generation EGFR tyrosine kinase inhibitors.
- Patients were randomly assigned to receive either ivonescimab plus platinum-doublet chemotherapy or placebo plus chemotherapy.
- The dual primary endpoints of the trial were progression-free survival (PFS) and OS in the intent to treat population.
- Key secondary endpoints included overall response rate, incidence and severity of adverse events (AEs), duration of response (DOR), observed concentrations of ivonescimab, and the number of patients who develop detectable anti-drug antibodies.
Efficacy Results
- Results showed that ivonescimab demonstrated a median OS of 16.8 months compared to 14 months in the placebo arm (HR 0.79; 95% CI: 0.62–1.01; p=0.057), narrowly missing statistical significance per the prespecified threshold.
- A longer-term follow-up of Western patients increased median follow-up to 13.7 months, reinforcing the OS benefit (HR 0.78; 95% CI: 0.62–0.98; nominal p=0.0332), with median OS of 17 months compared to 14 months in the placebo group.
- Median PFS was 6.8 months in the treatment ground compared to 4.4 months in the placebo group.
- Notably, PFS among European and North American patients treated with ivonescimab was 33% (hazard ratio 95% CI: 0.45-1.00) compared to 45% among Chinese patients.
- ORR for the treatment group was 45% compared to 34% in the placebo group.
- The median DOR for the treatment group was 7.6 months compared to 4.2 months in the placebo group.
Safety Findings
- Safety findings were consistent with prior studies, with the treatment reported to be well tolerated.
- The most common treatment-related AEs included anemia and decreases in white blood cell, neutrophil, and platelet counts, with <1% of patients experiencing grade ≥3 hemorrhage events.1,2
NSCLC Context
- According to the American Cancer Society, NSCLC accounts for 87% of all lung cancers.
- Lung cancer as a whole is the second most common form of cancer in both men and women, with only prostate and breast cancer being more common.
- In the United States, lung cancer is the leading cause of cancer-related deaths, accounting for approximately 20% of all mortalities.3
Future Outlook and Gratitude
“With the results from HARMONi and continued upcoming catalysts from further HARMONi-2 and HARMONi-6 readouts, ivonescimab is well positioned to begin to realize its potential in changing the worldwide treatment landscape for cancer patients,” said Maky Zanganeh, president, co-CEO, Summit Therapeutics, in the press release. “But to focus on today and the presentation of the HARMONi trial, we would like to reiterate our sincere gratitude to the patients, physicians, nurses, and caregivers who participated in and regulatory authorities who supported this clinical study. Without the dedication of our investigators and courage of the patients willing to participate in clinical trials, it would be impossible to bring the potential next generation of therapies to those with cancer.”
References
- Longer-Term Follow-Up of Western Patients Showed Improving, Favorable Trend in Overall Survival in Global Phase III HARMONi Clinical Trial for Ivonescimab Plus Chemotherapy in 2L+ EGFRm NSCLC. Summit. September 7, 2025. Accessed September 8, 2025. https://www.smmttx.com/pressrelease/https-www-smmttx-com-wp-content-uploads-2025-09-2025_pr_0907_wclc-harmoni-data-_-final-pdf/
- Phase III Study of AK112 for NSCLC Patients. Clinicaltrials.gov. Accessed September 8, 2025. https://clinicaltrials.gov/study/NCT06396065?term=HARMONi%20&aggFilters=phase:3&rank=1
- Key Statistics for Lung Cancer. American Cancer Society. Accessed September 8, 2025. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html
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