Takeda, Innovent Advance IBI363 With Strong Survival Data in Resistant NSCLC

Innovent Biologics presented updated Phase 1 results for IBI363 (TAK-928), its first-in-class PD-1/IL-2α-bias bispecific fusion protein, at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. The ongoing study (NCT05460767), conducted in China, enrolled 136 patients with advanced non-small cell lung cancer (NSCLC) resistant to prior immunotherapy. Patients received doses ranging from 2 μg/kg weekly to 4 mg/kg every three weeks.

Mechanism of Action

IBI363 combines PD-1 blockade with selective IL-2 pathway activation. The molecule maintains affinity for IL-2 receptor alpha while reducing interaction with IL-2 receptor beta and gamma, helping enhance anti-tumor immune activity while limiting the toxicity historically associated with IL-2 therapies. This dual mechanism may restore anti-tumor immune responses in patients whose tumors have progressed after immunotherapy. For patients with immunotherapy-resistant NSCLC and no actionable driver mutations, standard chemotherapy provides only modest benefit, underscoring the need for novel approaches.

Survival Outcomes

Among 67 patients with EGFR wild-type squamous NSCLC, the 3 mg/kg every-three-weeks cohort delivered the strongest outcomes. Median progression-free survival (PFS) reached 10.1 months, while median overall survival (OS) reached 18.2 months. The estimated 24-month OS rate was 47.8%, indicating a durable survival benefit in a difficult-to-treat population. For comparison, standard chemotherapy such as docetaxel typically yields median OS of 7–10 months, highlighting the potential clinical impact of IBI363.

In 58 patients with EGFR wild-type adenocarcinoma NSCLC, the same dose achieved a median PFS of 4.2 months and median OS of 15.2 months. The 24-month OS rate reached 42.7%. Smoking history appeared to influence outcomes, with patients across dose groups achieving a median OS of 23.4 months, suggesting a potential subgroup more likely to benefit.

Safety Profile

Long-term follow-up showed a manageable safety profile. Grade 3 or higher treatment-emergent adverse events occurred in 30.6% of patients receiving 1 to 1.5 mg/kg and 64.9% of those receiving 3 mg/kg. The most common adverse events were arthralgia, anemia, and rash. Most events were mild to moderate, and investigators reported no new safety signals during extended follow-up.

Clinical Implications

Professor Jianya Zhou of The First Affiliated Hospital, Zhejiang University School of Medicine highlighted the significant unmet need for patients who progress after immunotherapy. He noted that more than 40% of patients treated with 3 mg/kg remained alive beyond two years regardless of tumor histology, supporting the potential for durable long-term survival benefits.

Global Development

IBI363 is currently being evaluated in a pivotal Phase 2 melanoma study and a global Phase 3 trial in immunotherapy-resistant squamous NSCLC. The therapy has received two Fast Track Designations from the U.S. FDA and three Breakthrough Therapy Designations from China’s NMPA.

Under a 2025 collaboration agreement, Innovent and Takeda are jointly developing IBI363 globally and plan to co-commercialize the therapy in the United States. The ASCO 2026 presentation aligns with broader conference themes of overcoming resistance in NSCLC, positioning IBI363 among the most closely watched emerging therapies.

Reference

Innovent Presents Long-Term Follow-up Results from the PoC Study of IBI363 (TAK-928) (PD-1/IL-2α-bias bispecific fusion protein), Showing Robust Survival Benefits in Advanced Immunotherapy-Resistant Non-Small Cell Lung Cancer