Innovent reports IBI363 Phase Ib results at ESMO 2026, including a 60% lower risk of progression or death in immunotherapy-resistant lung cancer.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
Innovent Biologics has reported three clinical data updates for IBI363, also known as TAK-928, at the 2026 European Society for Medical Oncology (ESMO) Congress. The findings come from three Phase Ib studies evaluating the investigational PD-1/alpha-biased interleukin-2 (IL-2) bispecific fusion protein in first-line advanced non-small cell lung cancer (NSCLC), first-line HER2-negative gastric or gastroesophageal junction adenocarcinoma (G/GEJA), and immunotherapy-resistant lung adenocarcinoma.
IBI363 is being jointly developed by Innovent and Takeda. The studies evaluated the drug in combination with platinum-based chemotherapy, capecitabine and oxaliplatin (XELOX), and bevacizumab across different treatment settings.
First-Line NSCLC: Response Rates Across Three Dose Groups
The first Phase Ib proof-of-concept study evaluated IBI363 combined with platinum-based doublet chemotherapy (PDC) as first-line treatment for locally advanced or metastatic NSCLC (Abstract 1044P).
As of April 7, 2026, 80 patients had been enrolled, including 11 in the safety run-in phase and 69 in dose optimisation. Patients in the dose-optimisation phase had PD-L1 tumour proportion scores (TPS) below 50% and were randomised in a 1:1:1 ratio across three dose groups. Median follow-up was 8.9 months, and 48.8% of patients remained on treatment at the data cutoff.
Among patients with PD-L1-negative or PD-L1-low disease, confirmed objective response rates (cORR) were 47.4%, 61.9% and 86.4% with IBI363 doses of 1.5 mg/kg, 3 mg/kg and 3→1.5 mg/kg, respectively. Corresponding disease control rates (DCR) were 94.7%, 100% and 100%. Progression-free survival (PFS) data remained immature.
The combination maintained a manageable safety profile, with no new safety signals. The most frequently reported treatment-emergent adverse events (TEAEs) were anaemia (82.5%), decreased neutrophil count (76.3%), decreased white blood cell count (66.3%) and decreased platelet count (46.3%). A second-stage randomised study comparing IBI363 plus chemotherapy with pembrolizumab plus chemotherapy is ongoing.
First-Line G/GEJA: Responses Across PD-L1 CPS Subgroups
The second Phase Ib study evaluated IBI363 combined with XELOX in previously untreated HER2-negative advanced G/GEJA (Abstract 1008RO; NCT06610799).
As of July 9, 2026, 46 patients had been enrolled, including seven in dose escalation and 39 in dose expansion. Distant metastases were present in 97.8% of patients, including liver metastases in 45.7% and peritoneal metastases in 28.3%.
Among 42 patients with at least one post-baseline tumour assessment, cORR was 78.6% and DCR was 100%. In the dose-expansion cohort receiving IBI363 at 1.5 mg/kg (n=35), cORR was 80% and DCR was 100%. Response rates were 90% among patients with PD-L1 combined positive score (CPS) ≥5 and 76.9% among those with CPS below 5.
The overall population had 12-month PFS and overall survival (OS) rates of 52.8% and 84.5%, respectively. In the dose-expansion cohort, the corresponding rates were 55.2% and 84.5%. These estimates remain immature, with follow-up ongoing.
Grade 3 or higher TEAEs occurred in 45.7% of the overall population. Common events included anaemia (69.6%), decreased platelet count (60.9%) and decreased neutrophil count (43.5%). No treatment-related deaths were reported. A randomised proof-of-concept study is planned to further evaluate the combination.
Immunotherapy-Resistant Lung Cancer: Significant PFS Improvement
The third study was the first randomised controlled Phase Ib evaluation of IBI363 in immunotherapy-resistant NSCLC (Abstract 1952RO; NCT06468098). It compared IBI363 plus bevacizumab with docetaxel in patients with locally advanced, unresectable or metastatic lung adenocarcinoma without actionable genomic alterations whose disease had progressed following prior immunotherapy.
As of July 6, 2026, median follow-up was 8.48 months in the combination group and 7.59 months in the docetaxel group. The cORR was 20.0% with IBI363 plus bevacizumab compared with 7.1% with docetaxel.
Median PFS was significantly prolonged with the combination, with a hazard ratio of 0.40 (P=0.0006), corresponding to a 60% reduction in the risk of disease progression or death. PFS benefit was observed regardless of PD-L1 expression, while OS data remained immature.
Grade 3 or higher TEAEs occurred in 62.2% of patients receiving IBI363 plus bevacizumab and 78.0% receiving docetaxel. The most common adverse events in the combination group were arthralgia (53.3%), anaemia (48.9%) and rash (46.7%). No treatment-related deaths occurred in the combination group, compared with one in the docetaxel group.
Although baseline characteristics were generally balanced, the docetaxel group included higher proportions of patients with a smoking history and PD-L1 expression of at least 1%, relevant considerations when interpreting the comparative findings.
Mechanism and Global Development
IBI363 is an investigational PD-1/alpha-biased IL-2 bispecific fusion protein designed to combine PD-1 blockade with selective IL-2 pathway activation. Its IL-2 component retains affinity for IL-2 receptor alpha (IL-2Rα) while reducing binding to IL-2Rβ and IL-2Rγ, aiming to limit broader immune activation. Its PD-1-binding component blocks the PD-1/PD-L1 pathway and is designed to direct IL-2 activity towards tumour-associated T cells.
The global development programme includes MarsLight-11 (NCT07217301), a Phase III study evaluating IBI363 monotherapy in immunotherapy-resistant NSCLC. The drug has also received two Fast Track Designations from the US Food and Drug Administration and three Breakthrough Therapy Designations from China’s National Medical Products Administration.
Under their October 2025 collaboration agreement, Innovent and Takeda are jointly developing IBI363 globally. The companies will co-commercialise the drug in the United States, while Takeda holds exclusive commercialisation rights outside the United States and Greater China. Development costs are shared 60:40 between Takeda and Innovent.
Clinical Interpretation
The three ESMO updates provide evidence of antitumour activity across different treatment settings. The first-line NSCLC and G/GEJA studies report encouraging response rates, but their early-phase designs and immature survival data limit conclusions about comparative efficacy and long-term benefit.
The randomised immunotherapy-resistant lung cancer study provides the strongest comparative finding, with significantly prolonged PFS against docetaxel. However, the Phase Ib results require confirmation through larger studies, and mature OS data are still awaited.
The ongoing Phase III development programme will be important in determining whether the observed PFS benefit translates into a clinically meaningful treatment advantage in immunotherapy-resistant NSCLC.
Reference
Innovent Biologics. 2026 ESMO | Innovent Presents Multiple Clinical Data Updates for IBI363/TAK-928, a PD-1/Alpha-Biased IL-2 Bispecific Fusion Protein. Published October 26, 2026.
Study of IBI363 in Patients with Advanced First-line Gastric Cancer, ClinicalTrials.gov ID NCT06610799
A Study of IBI363 in Subjects with Advanced Malignancies, ClinicalTrials.gov ID NCT06468098
About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.