Abstract 68P
Background
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.
Methods
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.
Results
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: 68P
| TRAES ≥10% | % |
| Proteinuria | 33 |
| Rash | 22 |
| Epistaxis | 21 |
| Transaminase increase | 18 |
| Amylase increased | 18 |
| Anaemia | 16 |
| Hypoaesthesia | 16 |
| Decreased appetite | 16 |
| Hypothyroidism | 16 |
| WBC count decreased | 16 |
| Hyperuricaemia | 15 |
| Pruritus | 15 |
| Blood pressure increased | 13 |
| Hypertension | 13 |
| Infusion related reaction | 13 |
| Neutrophil count decreased | 13 |
| Alopecia | 11 |
| Haemoptysis | 11 |
| Lipase increased | 11 |
| Platelet count decreased | 11 |
Conclusions
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.
Clinical trial identification
NCT04736823.
Legal entity responsible for the study
Akeso.
Funding
Akeso.
Disclosure
L. Zhang: Financial Interests, Institutional, Research Grant: Hengrui, BeiGene, Xiansheng, Eli Lilly, Novartis, Roche, Hansoh, Bristol Myers Squibb; Financial Interests, Institutional, Advisory Role: MSD, BeiGene, Xiansheng. Y. Xia: Financial Interests, Institutional, Full or part-time Employment: Akeso. All other authors have declared no conflicts of interest.