A Study of Ivonescimab in First-Line ES-SCLC

A Phase II Clinical Study of Ivonescimab Combination Therapy as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer (ES-SCLC)

The goal of this clinical trial is to learn if different combinations of a drug called Ivonescimab, along with chemotherapy and other investigational drugs, are safe and effective for the initial treatment of adults with extensive-stage small cell lung cancer (ES-SCLC).

The main questions the study aims to answer are:

• What side effects do participants experience from these combination treatments?
• How well do the treatments work to shrink tumors?

Researchers will compare three groups to see which combination works best. All participants will receive Ivonescimab and chemotherapy (etoposide and carboplatin). The differences are:

• Group 1 will also receive an additional drug called AK117.
• Group 2 will also receive a different additional drug called Cadonilimab.
• Group 3 will receive Ivonescimab and chemotherapy only.

Participants will:

• Be assigned by chance to one of the three groups.
• Undergo an initial treatment phase (about 3 months), receiving chemotherapy plus the specific study drugs for their group.
• If the treatment is effective and side effects are manageable, continue with a maintenance phase using only the study drugs (without chemotherapy) for up to 2 years.
• Attend regular clinic visits for check-ups, blood tests, and imaging scans (like CT scans) to see how they are responding to the treatment.

Study Overview

• Status: Recruiting
• Conditions: Extensive-stage Small Cell Lung Cancer (ES-SCLC)
• Intervention / Treatment: Drug: Ivonescimab; Drug: AK117; Drug: Etoposide; Drug: Carboplatin (AUC 5); Drug: Cadonilimab

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wenting Li; Phone Number: +86-18116403289; Email: wenting01.li@akesobio.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100020
      • Not yet recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
      • Contact: Zhijie Wang, MD, PhD; Phone Number: +86-10-87788525; Email: wangzj@cicams.ac.cn
      • Principal Investigator: Zhijie Wang, MD, PhD
  • Shaanxi
    • Xi'an, Shaanxi, China, 710000
      • Recruiting
      • The First Affiliated Hospital of Xi'an Jiaotong University
      • Contact: Yu Yao, MD, PhD; Phone Number: +86-13572101611; Email: 13572101611@163.com
      • Principal Investigator: Yu Yao, MD, PhD
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200433
      • Recruiting
      • Shanghai Pulmonary Hospital Affiliated to Tongji University
      • Contact: Shengxiang Ren, MD, PhD; Phone Number: +86-21-65102117; Email: harry_ren@126.com
      • Principal Investigator: Shengxiang Ren, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically or cytologically confirmed extensive-stage small cell lung cancer (ES-SCLC).
• No prior systemic therapy for ES-SCLC.
• At least one measurable lesion as defined by RECIST v1.1.
• Age 18 to 75 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function.

Exclusion Criteria:

• Active or untreated central nervous system (CNS) metastases (Treated, stable brain metastases are allowed).
• History of severe hypersensitivity to monoclonal antibodies.
• Active autoimmune disease requiring systemic treatment within the past 2 years.
• Significant cardiovascular disease.
• Active hepatitis B or C, or HIV infection.
• Interstitial lung disease or non-infectious pneumonitis.
• Significant bleeding tendency or risk, including tumor invasion of major blood vessels.
• Pregnancy or lactation.
• Other active malignancies within 5 years prior to enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ivonescimab + AK117 + Chemotherapy	Drug: Ivonescimab; Administered intravenously at a specified dose and frequency.; Drug: AK117; Administered intravenously at a specified dose and frequency.; Drug: Etoposide; Administered intravenously at 100 mg/m² on Days 1-3 of each 3-week cycle for 4 cycles.; Drug: Carboplatin (AUC 5); Administered intravenously at AUC 5 on Day 1 of each 3-week cycle for 4 cycles.
Experimental: Ivonescimab + Cadonilimab + Chemotherapy	Drug: Ivonescimab; Administered intravenously at a specified dose and frequency.; Drug: Etoposide; Administered intravenously at 100 mg/m² on Days 1-3 of each 3-week cycle for 4 cycles.; Drug: Carboplatin (AUC 5); Administered intravenously at AUC 5 on Day 1 of each 3-week cycle for 4 cycles.; Drug: Cadonilimab; Administered intravenously at a specified dose and frequency.
Experimental: Ivonescimab + Chemotherapy	Drug: Ivonescimab; Administered intravenously at a specified dose and frequency.; Drug: Etoposide; Administered intravenously at 100 mg/m² on Days 1-3 of each 3-week cycle for 4 cycles.; Drug: Carboplatin (AUC 5); Administered intravenously at AUC 5 on Day 1 of each 3-week cycle for 4 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The proportion of participants achieving a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR), as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	Up to approximately 2 years.
Incidence of Adverse Events (AEs)	The number and percentage of participants experiencing any Adverse Event (AE). An AE is defined as any untoward medical occurrence in a participant administered a study drug, which may not have a causal relationship with the treatment. Severity will be graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.	From first dose up to 90 days after last dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)	The proportion of participants achieving a BOR of CR, PR, or Stable Disease (SD), as assessed by the investigator per RECIST v1.1.	Up to approximately 2 years.
Duration of Response (DoR)	For responders (participants achieving CR or PR), DoR is defined as the time from the first documented evidence of CR or PR until the first documented disease progression or death from any cause, whichever occurs first, per RECIST v1.1.	Up to approximately 2 years.
Time to Response (TTR)	For responders (participants achieving CR or PR), TTR is defined as the time from the start of study treatment to the first documented objective response (CR or PR), per RECIST v1.1.	Up to approximately 2 years.
Progression-Free Survival (PFS)	PFS is defined as the time from the start of study treatment to the first documented disease progression per RECIST v1.1 or death from any cause, whichever occurs first.	Up to approximately 2 years.
Overall Survival (OS)	OS is defined as the time from the start of study treatment to death from any cause.	Up to approximately 5 years.
Serum concentrations of Ivonescimab, Cadonilimab, and AK117	Serum concentrations of Ivonescimab, Cadonilimab, and AK117 will be measured to characterize the pharmacokinetic (PK) profiles.	Up to approximately 2 years.
Incidence of Anti-drug Antibodies (ADA)	The immunogenicity will be assessed by the incidence of participants who develop detectable anti-drug antibodies (ADA) against Ivonescimab, Cadonilimab, and/or AK117.	Up to approximately 2 years.

Collaborators and Investigators

• Sponsor: Akeso

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: September 29, 2025
• First Submitted That Met QC Criteria: November 17, 2025
• First Posted (Actual): November 24, 2025

Study Record Updates

• Last Update Posted (Actual): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: November 1, 2025

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; Small Cell Lung Carcinoma; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Coordination Complexes; Etoposide; Carboplatin
• Other Study ID Numbers: AK112-214

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No