Ivonescimab extends PFS vs. pembrolizumab in advanced NSCLC, may be ‘a new standard’
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Key takeaways:
- Results showed longer median PFS and a higher 9-month PFS with ivonescimab than pembrolizumab.
- Patients with liver metastases, brain metastases or squamous NSCLC derived a PFS benefit from ivonescimab.
Ivonescimab significantly improved PFS compared with pembrolizumab as first-line treatment of PD-L1-positive advanced non-small cell lung cancer, according to results of the HARMONi-2 trial.
The findings — presented at International Association for the Study of Lung Cancer (IASLC) — showed a near-doubling of median PFS with ivonescimab (SMT112, Summit Therapeutics) among patients with PD-L1 tumor proportion scores (TPS) of at least 1%.
“This is the first randomized phase 3 study to demonstrate a clinically meaningful significant improvement in efficacy with a novel drug compared [with] pembrolizumab in advanced non-small cell lung cancer,” Caicun Zhou, PhD, MD, director of the department of oncology at Shanghai Pulmonary Hospital and director of Cancer Institute of Tongji University Medical School, said during a presentation.
The results “highlight ivonescimab's potential as a new standard of care,” Zhou said in a press release.
Ivonescimab is an investigational bispecific antibody that targets PD-1 and VEGF.
The agent has showed clinical activity in early-phase studies as front-line therapy for certain patients with advanced NSCLC.
Zhou and colleagues conducted HARMONi-2 to compare the efficacy of ivonescimab and pembrolizumab (Keytruda, Merck) as first-line treatment for patients with PD-L1-positive locally advanced or metastatic NSCLC.
All patients had stage IIIB to stage IV NSCLC with PD-L1 TPS of at least 1% and ECOG performance scores of 0 or 1. Study participants had no EGFR mutations or ALK rearrangements, and they had received no prior systemic therapy.
Researchers randomly assigned 198 patients to 20 mg/kg ivonescimab every 3 weeks. The other 200 patients received 200 mg pembrolizumab every 3 weeks.
Treatment continued for up to 24 months, or until unacceptable toxicity or no clinical benefit.
PFS per blinded independent radiographic review committee served as the primary endpoint. Secondary endpoints included OS, investigator-assessed PFS, objective response rate, duration of response, time to response and safety. Quality of life served as an exploratory endpoint.
Median follow-up was 8.67 months.
Results showed longer median PFS with ivonescimab than pembrolizumab (11.14 months vs. 5.82 months; stratified HR = 0.51; 95% CI, 0.38-0.69).
A higher percentage of patients assigned ivonescimab remained progression free at 9 months (56% vs. 40%).
The PFS benefit persisted within prespecified subgroups, including patients with squamous NSCLC (HR = 0.5; 95% CI, 0.33-0.76) and nonsquamous NSCLC (HR = 0.55; 95% CI, 0.36-0.84); those with PD-L1 TPS of 1% to 49% (HR = 0.54; 95% CI, 0.37-0.78) and those with PD-L1 TPS of 50% or higher (HR = 0.48; 95% CI, 0.29-0.79); those with liver metastases (HR = 0.47; 95% CI 0.23-0.98) and those with brain metastases (HR = 0.55; 95% CI, 0.28-1.05).
Researchers also reported a higher ORR (50% vs. 38.5%) and a higher disease control rate (89.9% vs. 70.5%) in the ivonescimab group. Median duration of response had not been reached in either group.
A higher percentage of patients assigned ivonescimab experienced any-grade treatment-related adverse events (89.8% vs. 81.9%) and grade 3 or higher treatment-related adverse events (29.4% vs. 15.6%). Three patients (1.5%) assigned ivonescimab and six (3%) assigned pembrolizumab experienced treatment-related events that led to discontinuation. One (0.5%) assigned ivonescimab and two (1%) assigned pembrolizumab experienced treatment-related deaths that led to death.
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Zhou C, et al. Abstract 2700. Presented at: IASLC World Conference on Lung Cancer; Sept. 7-10, 2024; San Diego.
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