Ivonescimab in Combination With Docetaxel in Advanced Non-Small Cell Lung Cancer (NSCLC)

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 is a Phase 3 Randomized, double-blind, Multicenter Study of Ivonescimab Combined with Docetaxel 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. The purpose of this study is to evaluate the efficacy and safety of ivonescimab versus placebo, combined with docetaxel in patients with advanced NSCLC.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Ivonescimab, docetaxel; Drug: Placebo, docetaxel

• Study Type: Interventional
• Enrollment (Estimated): 536
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Wenting Li; Phone Number: 18116403289; Email: wenting01.li@akesobio.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Recruiting
      • Shanghai East Hospital
      • Contact: Caicun Zhou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ivonescimab and docetaxel	Drug: Ivonescimab, docetaxel; Patients will receive ivonescimab and docetaxel as an IV injection; Other Names: AK112, docetaxel
Active Comparator: Placebo and docetaxel	Drug: Placebo, docetaxel; Patients will receive placebo and docetaxel as an IV injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall Survival (OS) in the FAS population	approximately 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Progression Free Survival (PFS) assessed by investigator based on RECIST V1.1	approximately 3 years
Adverse Event (AE)	Incidence and severity of adverse events (AEs) and clinically significant abnormal laboratory test results	From the patient signs the ICF to 30 days (AE) and 90 days (SAE) after the last dose of study treatment or initiation of other anticancer therapy, whichever occurs first

Collaborators and Investigators

• Sponsor: Akeso
• Investigators: Principal Investigator: Caicun Zhou, Shanghai East Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: April 8, 2025
• First Submitted That Met QC Criteria: April 8, 2025
• First Posted (Actual): April 15, 2025

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel
• Other Study ID Numbers: AK112-305 (HARMONi-8A)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No