68P Phase II results of ivonescimab (ivo) a novel PD-1/VEGF bispecific in combination with chemotherapy for first-line treatment of patients (pts) with advanced/metastatic squamous (Sq) non-small cell lung cancer (NSCLC)

Ivo is a bispecific antibody with cooperative binding to enhance binding affinity to PD-1 by >18 fold and VEGF by >4 fold with the potential to drive synergistic anti-tumor activity. Ivo has a mean T1/2 of 6-7 days. We aimed to assess the efficacy and safety of ivo combined with chemotherapy as first line treatment of advanced Sq-NSCLC. Updated data from an open-label, multi-center phase II study, previously reported at ASCO 2023, assessing the efficacy and safety of ivo+chemo, in pts receiving first line therapy for advanced Sq-NSCLC. Pts were treated with 10 mg/kg (n=10) or 20 mg/kg(n=53) ivo q3wks combined with carboplatin and pemetrexed (non-Sq) or carboplatin and paclitaxel (Sq). Pts were excluded if they had tumor encircling blood vessels, necrosis and cavitation, or had central, cavitary sq NSCLC, or risk of hemorrhage. The primary endpoint was ORR per RECISTv1.1 by investigator. 63 pts with advanced Sq-NSCLC received ivo plus chemotherapy. Median age was 59 yrs. 3% and 97% pts had ECOG PS 0 and 1, respectively, and 8% of pts had baseline brain metastasis. Median follow-up was 21.0 mo. Pts with Sq-NSCLC experienced a 71.4% ORR with median DOR 12.7 mo, 90.5% DCR, the median PFS 11.1 mo, and 21-mo OS rate was 69.5%. The table lists the most common treatment related adverse events (TRAEs) ≥ 10%. Grade ≥3 TRAEs occurred in 44.4%, TRAEs leading to discontinuation occurred in 11.1% of pts. Overall incidence of bleeding events was 46% (grade 1-2) with one grade ≥3 event (hemoptysis) at 10mg/kg dose.Table: 68PTRAES ≥10%%Proteinuria33Rash22Epistaxis21Transaminase increase18Amylase increased18Anaemia16Hypoaesthesia16Decreased appetite16Hypothyroidism16WBC count decreased16Hyperuricaemia15Pruritus15Blood pressure increased13Hypertension13Infusion related reaction13Neutrophil count decreased13Alopecia11Haemoptysis11Lipase increased11Platelet count decreased11 Open table in a new tab Ivonescimab plus chemotherapy has promising anti-tumor activity in pts with advanced NSCLC and was administered safely in combination with platinum doublet chemotherapy to pts with Sq histology.