A Study of AK138D1 Alone or in Combination With Ivonescimab in Advanced Non-Small Cell Lung Cancer

A Phase Ib/II Study of AK138D1 as Monotherapy and in Combination With Ivonescimab in Patients With Advanced Non-Small Cell Lung Cancer

The goal of this clinical trial is to evaluate the safety, tolerability, and efficacy of AK138D1 as monotherapy or in combination with ivonescimab in patients with advanced non-small cell lung cancer.

Participants will receive study treatment with AK138D1 alone or in combination with ivonescimab, undergo safety assessments and tumor evaluations, and be followed for treatment tolerability, antitumor activity, and clinical outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: AK138D1; Drug: Ivonescimab; Drug: Carboplatin

Detailed Description

This is a multicenter, open-label phase Ib/II study of AK138D1 as monotherapy or in combination with ivonescimab in patients with advanced non-small cell lung cancer. The phase Ib portion is designed to evaluate the safety, tolerability, and preliminary antitumor activity of AK138D1 in combination with ivonescimab. The phase II portion is designed to evaluate the safety and efficacy of AK138D1 as monotherapy or in combination with ivonescimab.

• Study Type: Interventional
• Enrollment (Estimated): 265
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xufang Yu; Phone Number: +86 (0760) 89873999; Email: clinicaltrials@akesobio.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Shanghai East Hospital
      • Contact: Caicun Zhou; Phone Number: +8613301825532; Email: caicunzhoudr@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. The subject must sign the written informed consent form (ICF) voluntarily;
2. At enrollment, aged ≥ 18 to ≤ 75 years, both males and females are eligible;
3. Has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
4. Has a life expectancy of ≥ 3 months;
5. Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
6. Has Stage IIIB/IIIC or IV NSCLC (American Joint Committee on Cancer [AJCC]).
7. Adequate organ function.

Exclusion Criteria:

1. Concomitant participation in another clinical study, unless it is a non-interventional clinical study or the follow-up period of an interventional study;
2. Presence of active central nervous system (CNS) metastases.
3. Live vaccines or attenuated live vaccines administered within 4 weeks prior to the first dose, or planned to be administered during the study; use of inactivated vaccines is allowed;
4. Untreated subjects with active hepatitis B or active hepatitis C;
5. Known active pulmonary tuberculosis (TB); subjects with suspected active TB must undergo appropriate clinical assessment to rule out the presence of active disease;
6. Known active syphilis infection;
7. Subjects with known allergy to any component of any study drug; and with a history of known severe hypersensitivity reactions to other monoclonal antibodies;
8. Other reasons for ineligibility as evaluated by investigator.

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: AK138D1; AK138D1 will be administered at pre-specified dose levels.	Drug: AK138D1; Enrolled subjects will receive intravenous infusion (IV) of AK138D1 according to the dosing regimen specified in their cohort.
Experimental: AK138D1+ Ivonescimab; AK138D1 and ivonescimab will be administered at pre-specified dose levels.	Drug: AK138D1; Enrolled subjects will receive intravenous infusion (IV) of AK138D1 according to the dosing regimen specified in their cohort.; Drug: Ivonescimab; Enrolled subjects will receive intravenous infusion (IV) of Ivonescimab according to the dosing regimen specified in their cohort.
Experimental: AK138D1 + Ivonescimab + Carboplatin; AK138D1, ivonescimab and carboplatin will be administered at pre-specified dose levels.	Drug: AK138D1; Enrolled subjects will receive intravenous infusion (IV) of AK138D1 according to the dosing regimen specified in their cohort.; Drug: Ivonescimab; Enrolled subjects will receive intravenous infusion (IV) of Ivonescimab according to the dosing regimen specified in their cohort.; Drug: Carboplatin; Enrolled subjects will receive intravenous infusion (IV) of Carboplatin according to the dosing regimen specified in their cohort.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)	Incidence and severity of subjects with adverse events	Up to approximately 2 years
Objective Response Rate (ORR)	Objective Response Rate (ORR) is the proportion of subjects with complete response (CR) or partial response (PR) , assessed by investigator according to RECIST v1.1.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-drug antibodies (ADA)	Number of subjects with detectable anti-drug antibodies (ADA).	Up to approximately 2 years
Overall Survival (OS)	Overall Survival (OS) is defined as the time from randomization to death due to any cause.	Up to approximately 2 years
Disease Control Rate (DCR)	Disease control rate (DCR) assessed by investigator according to RECIST v1.1.	Up to approximately 2 years
Duration of response (DoR)	Duration of response (DoR) assessed by investigator according to RECIST v1.1.	Up to approximately 2 years
Time to response (TTR)	Time to response (TTR) is defined as the time to response assessed by investigator according to RECIST v1.1.	Up to approximately 2 years
Progression Free Survival (PFS)	PFS is defined as the time from randomization to the first documented disease progression (per RECIST v1.1) assessed by investigator or death due to any cause, whichever occurs first.	Up to approximately 2 years
Pharmacokinetics (PK) characteristics	Serum drug concentration profiles at different time points after administration.	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Akeso

Study record dates

Study Major Dates

• Study Start (Estimated): June 18, 2026
• Primary Completion (Estimated): June 18, 2028
• Study Completion (Estimated): July 3, 2030

Study Registration Dates

• First Submitted: May 28, 2026
• First Submitted That Met QC Criteria: May 28, 2026
• First Posted (Actual): June 3, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer
• 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; Coordination Complexes; Carboplatin
• Other Study ID Numbers: AK138D1-201

Drug and device information, study documents

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