Randomized phase 3 study (MarsLight-11) evaluating IBI363 (TAK-928) versus docetaxel in patients (pts) with squamous non-small cell lung cancer (sqNSCLC) after prior chemotherapy (chemo) and immunotherapy (IO).

TPS8673 Background: In most series, sqNSCLC has worse clinical outcomes compared with non-squamous NSCLC with IO combinations. After chemo and IO failure, docetaxel±ramucirumab remains the standard of care for advanced sqNSCLC, but offers only short-lived disease control (median progression-free survival [PFS] of approximately 3–4 months), and high rates of severe toxicities. Thus, effective post-chemo and IO options for advanced sqNSCLC remain a significant unmet clinical need. IBI363 is a first-in-class, PD-1/IL-2 α-bias bispecific antibody fusion protein designed to block the PD-1/PD-L1 pathway and simultaneously activate the IL-2 pathway. It selectively expands and rejuvenates exhausted tumor-specific T cells by cis-activating IL-2 receptors. The IL-2 arm of IBI363 is engineered to retain its affinity for IL-2Rα while reducing binding to IL-2Rβ and IL-2Rγ thereby minimizing off-target toxicity. This dual mechanism has shown potential to address the unmet clinical needs of pts with IO-resistant and immune-cold tumors. In prior phase 1/2 studies, IBI363 monotherapy at 3 mg/kg every 3 weeks (Q3W) was well-tolerated and showed encouraging, durable efficacy in pts with advanced, IO-treated NSCLC and other solid tumors (2025 ASCO [8509, 2502 and 104]). Here, we present the trial in progress for MarsLight-11 (NCT07217301), a randomized, open-label, multi-regional Phase 3 study evaluating IBI363 versus docetaxel in pts with sqNSCLC after prior chemo and IO. Methods: This study is enrolling eligible pts with unresectable, locally advanced or metastatic sqNSCLC who have progressed on or after platinum-based chemo and anti-PD-1/PD-L1 treatments (defined as radiographic progression per RECIST v1.1 during or within 6 months after discontinuation of IO). Pts with known actionable genomic alterations, active or symptomatic brain metastases are excluded. Pts are randomized 1:1 to IBI363 or docetaxel (control). Stratification factors include the type of IO resistance (primary vs. acquired), the sequence of prior IO and chemo (concurrent vs. sequential), and region (Asia vs. non-Asia). Pts in the experimental arm will receive a priming dose of IBI363 (0.1 mg/kg) seven days prior to the first full dose (3 mg/kg Q3W). The control arm will receive docetaxel (75 mg/m² Q3W). The primary endpoint is overall survival (OS). Secondary endpoints include investigator-assessed PFS, objective response rate, disease control rate, duration of response, and time to response per RECIST v1.1, as well as safety, pharmacokinetics, and immunogenicity. One interim analysis (IA1) and one final analysis are planned for OS. The study plans to enroll approximately 600 pts globally, including sites in China, the United States, Canada, the European Union, the United Kingdom, Japan and South Korea. Clinical trial information: NCT07217301 .