Ivonescimab plus docetaxel for 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

This trial tests whether adding ivonescimab to docetaxel helps people with advanced or metastatic non-small cell lung cancer that progressed after PD-(L)1 inhibitor therapy.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 536 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Akeso (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, Ivonescimab
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06928389 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind Phase 3 trial comparing ivonescimab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic NSCLC who progressed on PD-(L)1 inhibitor–based therapy. Eligible participants have prior platinum chemotherapy, measurable disease by RECIST 1.1, ECOG performance status 0–1, and adequate organ function. Participants are randomized to receive ivonescimab or placebo in combination with standard docetaxel and are followed for efficacy and safety outcomes. The study is conducted across participating centers with blinded treatment assignment.

Who should consider this trial

Good fit: Adults 18–75 with histologically or cytologically confirmed locally advanced or metastatic NSCLC that progressed on PD-(L)1 inhibitor therapy, who have received prior platinum chemotherapy, have at least one measurable lesion, ECOG 0–1, and adequate organ function.

Not a fit: Patients with small cell lung cancer histology, known actionable genomic alterations, other malignancies within the past 3 years, prior exposure to the same immunotherapy target, poor performance status, or those unable to meet organ-function criteria are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, adding ivonescimab to docetaxel could slow disease progression and potentially extend survival compared with chemotherapy alone for patients who progressed after PD-(L)1 inhibitors.

How similar studies have performed: Combining novel antibodies with chemotherapy after PD-(L)1 failure is a relatively new approach with limited early-phase data for ivonescimab and mixed results reported for similar strategies.

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 targeting immune mechanisms other than PD-1/PD-L1 inhibitors.
* Previous treatment with docetaxel.
* History of severe bleeding tendency or coagulation dysfunction.
* Active autoimmune disease requiring systemic therapy within 2 years prior to randomization.
* History of myocarditis, cardiomyopathy, and malignant arrhythmia.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai East Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Caicun Zhou — Shanghai East Hospital
• Study coordinator: Wenting Li

Conditions Non-Small Cell Lung Cancer