Ivonescimab in Combination With Docetaxel in Advanced Non-Small Cell Lung Cancer
A Randomized, Double-blind, Multicenter Phase 3 Clinical Trial of Ivonescimab Versus Placebo, Combined With Docetaxel in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) That Has Progressed on or After PD-(L)1 Inhibitor-based Therapy
Sponsor: Akeso
No open prediction endpoints
Endpoints are classified and published by ProgramSignal analysts.
Request endpoint coverageKey Facts
Primary Endpoints (CT.gov)
Overall Survival (OS)
Time frame: approximately 5 years
Secondary Endpoints
Progression Free Survival (PFS)
Adverse Event (AE)
Eligibility Criteria
Inclusion Criteria: * Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures). * Age ≥ 18 years old and ≤ 75 years old at the time of randomization. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Expected life expectancy of at least 3 months. * Histologically or cytologically confirmed diagnosis of NSCLC. * Locally advanced or metastatic NSCLC (American Joint Committee on Cancer \[AJCC\] 8th edition). * Previously received systemic platinum-based chemotherapy and PD-1/L1 inhibitors. * At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. * Adequate organ function. Exclusion Criteria: * Histologic or cytopathologic evidence of the presence of small cell lung carcinoma. * Other malignancies within 3 years prior to randomization. * Known actionable genomic alterations. * Prior administration of any immunotherapy target…
Read full criteria on CT.gov →Analyst Commentary
🔬 Why This Trial Matters
This is a pivotal Phase 3 trial that could establish ivonescimab, Akeso's bispecific anti-PD-1/VEGF antibody, as a differentiated option in the highly competitive second-line NSCLC setting. The trial tests ivonescimab plus docetaxel against docetaxel alone in patients who have progressed after platinum-based chemotherapy and immunotherapy, addressing a significant unmet need in a population with limited effective options. With OS as the primary endpoint and a substantial 536-patient enrollment, this study is designed as a registrational trial that could support global regulatory filings if successful. The completion timeline extending to 2027 reflects the rigorous survival follow-up required, suggesting Akeso is aiming for a definitive survival benefit rather than an accelerated approval pathway.
📈 What the Readout Means for Investors
Investors should focus on whether ivonescimab demonstrates a clinically meaningful and statistically significant OS improvement over docetaxel monotherapy, with success likely requiring a hazard ratio below 0.75 and at least 3-4 months of median OS benefit to be commercially competitive. The bar is elevated because this is a post-immunotherapy population where historical response rates are typically below 15%, making any survival extension particularly valuable but difficult to achieve. A positive readout would validate the bispecific mechanism's potential to overcome resistance in IO-refractory disease and significantly expand ivonescimab's addressable market beyond first-line settings where it's already being developed. Trial failure would not be catastrophic given Akeso's other ongoing ivonescimab programs, but it would eliminate a key late-stage indication and raise questions about the bispecific's ability to deliver differentiated efficacy in resistant populations.
🏁 Competitive Context
Success in NCT06928389 would be commercially significant because it would extend ivonescimab beyond the frontline “better PD-1” story into the large and difficult post–PD-(L)1 NSCLC setting, where patients have already progressed after immunotherapy and treatment options remain unsatisfactory. A positive OS/PFS result versus docetaxel would support the thesis that PD-1/VEGF bispecific biology can still add value after checkpoint exposure, potentially positioning ivonescimab as a broader NSCLC backbone rather than a single-line competitor. The commercial upside would be especially meaningful if the benefit is survival-driven, tolerability is manageable, and the effect is consistent across histology and prior-treatment subgroups; a modest or PFS-only result would still be useful, but much less likely to change practice broadly.