Docetaxel’s median overall survival in immunotherapy-refractory NSCLC sits at roughly 12 months, and that benchmark has held for years despite repeated attempts to improve on it. Innovent and Takeda are now placing a larger bet that IBI363/TAK-928 can finally move that number, expanding their global Phase 3 MarsLight-11 trial to add non-squamous NSCLC patients alongside the squamous cohort already enrolled.
The expansion restructures MarsLight-11 (NCT07217301) into two independent substudies, each pitting IBI363 monotherapy against docetaxel in patients whose disease progressed on or after platinum-based chemotherapy and anti-PD-1/PD-L1 immunotherapy. Non-squamous tumors account for the majority of NSCLC cases, so the non-squamous substudy is the larger commercial prize. Running both histologies under one trial umbrella keeps the operational structure tight while nearly doubling the addressable population the program can speak to at registration.
What makes IBI363/TAK-928 worth watching as a control-arm challenger is its mechanism. The molecule blocks PD-1 while selectively delivering IL-2 to the tumor, and its IL-2 arm is engineered to retain affinity for IL-2Rα while reducing binding to the beta and gamma receptor subunits. That design aims to activate T cells in the tumor without the systemic toxicity that has historically made IL-2 therapies difficult to use. Phase 1 data presented at ASCO 2026 showed durable responses in heavily pretreated, immunotherapy-resistant NSCLC patients, which is the exact population MarsLight-11 targets. The molecule has also received two FDA Fast Track Designations and three Breakthrough Therapy Designations from China’s NMPA, suggesting regulators in both markets see the mechanism as addressing a real gap in second-line care.
The commercial architecture behind the trial matters too. Under a deal signed in October 2025, Innovent and Takeda co-develop IBI363/TAK-928 globally, co-commercialize it in the U.S., and Takeda holds exclusive commercialization rights everywhere else outside greater China. A positive readout in non-squamous disease would give Takeda a much wider label to sell into Western markets. The number to watch from here is response rate in the non-squamous substudy: if IBI363 can beat docetaxel’s roughly 13% ORR in this setting with a durable signal, the case for registration becomes straightforward.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
