Perioperative Ivonescimab Shows Promise in Resectable Lung Cancer Treatment
Phase 2 trial evaluates bispecific antibody efficacy in non-small cell lung cancer patients.
1Trial Overview and Objectives
This nonrandomized phase 2 trial investigated the efficacy of ivonescimab, a bispecific antibody targeting PD-1 and VEGF, in patients with resectable non-small cell lung cancer. Researchers evaluated two cohorts receiving perioperative ivonescimab either as monotherapy or combined with platinum-paclitaxel chemotherapy, followed by surgery and subsequent adjuvant ivonescimab treatment for all participants.
2Primary Endpoint Results
In the chemotherapy combination cohort, the major pathological response rate reached 70.1 percent, successfully exceeding the historical control rate of 41 percent. The monotherapy cohort achieved a 60 percent response rate. These findings indicate that the combination strategy effectively meets the primary efficacy endpoints required for further clinical development in lung cancer.
3Pathological Response Details
Among patients achieving a major pathological response, 97.9 percent in the combination cohort showed residual viable tumor levels of 5 percent or less. Pathological complete response rates were 50.7 percent for the combination group and 30 percent for the monotherapy group, demonstrating significant tumor regression across the study population during the neoadjuvant phase.
4Surgical and Resection Outcomes
All patients who underwent surgery, totaling 10 in the monotherapy group and 67 in the combination group, achieved R0 resection, meaning no visible tumor remained at the margins. Lobectomy was the most frequent surgical procedure performed, accounting for 100 percent of surgeries in the monotherapy cohort and 89.6 percent in the combination cohort.
5Safety Profile and Adverse Events
Grade 3 or higher treatment-related adverse events occurred in 30.4 percent of the combination cohort and 36.4 percent of the monotherapy group. Common issues included decreased neutrophil and white blood cell counts. No treatment-related deaths were reported, and surgery-related adverse events linked to ivonescimab were generally manageable with no grade 3 events.
6VEGF-Related Side Effects
Adverse events potentially linked to VEGF blocking occurred in 29.1 percent of the combination cohort and 45.5 percent of the monotherapy group. Proteinuria was the most frequent side effect observed, though most cases remained at grade 1 or 2. Only a small percentage of patients experienced grade 3 or higher proteinuria during treatment.
7Subgroup Analysis Findings
Patients with squamous carcinoma demonstrated substantially higher pathological response rates compared to those with nonsquamous carcinoma. Furthermore, stage II disease patients showed superior outcomes, with a 91.7 percent major pathological response rate and a 66.7 percent pathological complete response rate, highlighting potential variations in treatment efficacy based on specific histological and clinical characteristics.
8Clinical Downstaging Observations
Clinical tumor downstaging was observed in 34.2 percent of the combination cohort, while T-stage downstaging occurred in 67.1 percent of these patients. Although N-stage remained unchanged for most participants, nearly half of those with stable N-stage who underwent surgery achieved a pathological complete response, suggesting significant local tumor control despite limited nodal downstaging.
9Study Population Characteristics
The trial enrolled 90 patients with a median age of 64 years. Most participants presented with stage III disease and squamous cell carcinoma. A significant majority of patients in both cohorts had PD-L1 tumor proportion scores of at least 1 percent, reflecting the target population for this specific immunotherapy-based treatment approach.
10Treatment Completion Rates
At the data cutoff, 89.9 percent of the combination cohort and 90.9 percent of the monotherapy cohort completed the planned three or four cycles of neoadjuvant treatment. A total of 13 patients did not complete surgery due to various reasons, including patient requests, disease progression, or unrelated medical conditions occurring during the study period.
11Event-Free Survival Data
Median event-free survival data were not yet mature at the time of the data cutoff. However, the 12-month event-free survival rate was recorded at 83.3 percent for the combination cohort and 81.8 percent for the monotherapy cohort. Continued monitoring is required to determine the long-term survival benefits of this perioperative treatment regimen.
12Clinical Significance and Future
These data support perioperative ivonescimab as a promising strategy for resectable non-small cell lung cancer. By combining anti-VEGF therapy with PD-1 blockade, the treatment addresses both immune evasion and abnormal angiogenesis. Future reports will provide additional data on overall survival, pharmacokinetic profiles, and the correlation between tumor-infiltrating lymphocytes and long-term treatment efficacy.