Innovent’s IBI363 (TAK‑928), a first‑in‑class PD‑1/IL‑2α‑bias bispecific fusion protein co‑developed with Takeda, shows high response rates in PD‑L1‑low first‑line NSCLC and durable survival in immunotherapy‑resistant disease. Updated Phase 1 data highlight improved tolerability with adaptive dosing and reinforce the dual mechanism of checkpoint blockade plus cytokine agonism.
Written By: Farha Farheen, PharmD
Reviewed By: Pharmacally Editorial Team
Innovent Biologics has presented updated proof‑of‑concept data for IBI363 (TAK‑928), a first‑in‑class PD‑1/IL‑2α‑bias bispecific fusion protein co‑developed globally with Takeda. The therapy is designed to block PD‑1 signaling while selectively activating IL‑2Rα, thereby enhancing anti‑tumor immune activity with reduced systemic toxicity.
The latest results highlight encouraging efficacy in PD‑L1‑low tumors and durable survival outcomes in patients whose disease progressed after prior immunotherapy, reinforcing the therapeutic rationale of combining checkpoint blockade with cytokine agonism.
First‑Line NSCLC: High Response in PD‑L1‑Low Disease
In a Phase 1 study, 80 patients with advanced or metastatic NSCLC lacking EGFR, ALK, or ROS1 alterations were enrolled. A majority had PD‑L1‑low disease, including 65.2% with tumor proportion scores below 1%. Among 22 evaluable patients treated with a step‑down regimen of 3 mg/kg in cycle one followed by 1.5 mg/kg every three weeks, investigators reported an objective response rate of 86.4%, a confirmed ORR of 81.8%, and a disease control rate of 100%. Responses were consistent across squamous and non‑squamous histologies, underscoring the broad activity of the regimen in PD‑L1‑low disease.
Safety Profile: Adaptive Dosing Advantage
Safety outcomes favored the adaptive dosing strategy. Grade 3 or higher treatment‑related adverse events occurred in 65.2% of patients receiving the 3→1.5 mg/kg regimen compared with 93.1% in the continuous 3 mg/kg group. Common toxicities included anemia, neutrophil reduction, leukopenia, arthralgia, and thrombocytopenia. Investigators emphasized that while hematologic events remained frequent, the relative reduction in high‑grade toxicities with adaptive dosing improved overall tolerability.
Immunotherapy‑Resistant NSCLC: Durable Survival Outcomes
Extended follow‑up from a separate Phase 1 study in 136 patients with immunotherapy‑resistant NSCLC further demonstrated durable survival benefits. In squamous NSCLC, the 3 mg/kg every‑three‑week regimen achieved a median progression‑free survival of 10.1 months and a median overall survival of 18.2 months (95% CI 10.7–not estimable), with a 24‑month overall survival rate of 47.8%. Among patients with EGFR wild‑type adenocarcinoma, median overall survival reached 15.2 months, while smokers demonstrated particularly strong outcomes with median overall survival extending to 23.4 months across dose groups. Long‑term safety remained manageable, with no new signals observed during follow‑up.
Executive Perspective
Dr. Hui Zhou, Chief R&D Officer of Innovent’s oncology pipeline, stated that the data support IBI363’s ability to generate durable immune activation in both treatment‑naïve and immunotherapy‑resistant NSCLC. He noted that the emerging long‑tail survival effect further validates the dual mechanism of immune checkpoint blockade and cytokine agonism.
Clinical Development Path
The first‑line NSCLC program has now advanced into a randomized head‑to‑head study comparing IBI363 plus chemotherapy against pembrolizumab plus chemotherapy across all PD‑L1 expression levels. Meanwhile, the global Phase 3 MarsLight‑11 trial is underway in immunotherapy‑resistant squamous NSCLC, with a separate Phase 3 study planned for non‑squamous disease pending regulatory discussions. IBI363 has already received two U.S. FDA Fast Track designations and three Breakthrough Therapy designations from China’s NMPA, underscoring its potential as a novel immunotherapy option in lung cancer.
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About the Writer
Farha Farheen, PharmD (LinkedIn) is a pharmacy professional with a strong interest in pharmacovigilance and clinical research. She has completed her Doctor of Pharmacy (Pharm.D) along with her internship as a Clinical Pharmacist. She has hands-on experience in adverse drug reaction (ADR) reporting, safety data documentation, and pharmacovigilance workflows, and is proficient in using VigiFlow. She is also a patent holder for an antibacterial formulation enriched with bioactive substances, granted by the German Patent and Trademark Office.