A Study of AK138D1 Alone or in Combination With Ivonescimab in Advanced Breast Cancer

A Phase Ib/II Study of AK138D1 as Monotherapy and in Combination With Ivonescimab in Patients With Advanced Breast 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 breast 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: Breast Cancer
• Intervention / Treatment: Drug: AK138D1; Drug: Ivonescimab; Drug: treatment of physician's choice

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 breast 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): 286
• Phase: Phase 2; Phase 1

Contacts and Locations

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

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Cancer Hospital Chinese Academy of Medical Sciences
      • Contact: Fei Ma
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Harbin Medical University Cancer Hospital
      • Contact: Tong Liu
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital of Sichuan University
      • Contact: Ting Luo

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. ECOG performance status score of 0 or 1;
4. Has a life expectancy of ≥ 3 months;
5. At least 1 measurable lesion as per RECIST v1.1 that is suitable for repeated accurate measurement.
6. 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 the 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.
Active Comparator: Treatment of Physician's Choice; Treatment of physician's choice will be administered according to one of the protocol-specified regimens selected by the investigator.	Drug: treatment of physician's choice; Enrolled subjects will receive treatment of physician's choice according to one of the protocol-specified regimens selected by the investigator, based on the investigator's decision.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)	Incidence and severity of participants with adverse events	Up to approximately 2 years
Overall Response Rate (ORR) assessed by investigator per RECIST v1.1	ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on 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
Disease Control Rate (DCR) assessed by investigator per RECIST v1.1	Disease control rate (DCR) assessed according to RECIST v1.1.	Up to approximately 2 years
Duration of response (DoR) assessed by the investigator per RECIST v1.1	Duration of response (DoR) assessed according to RECIST v1.1.	Up to approximately 2 years
Time to response (TTR) assessed by the investigator per RECIST v1.1	Time to response (TTR) is defined as the time to response based on RECIST v1.1.	Up to approximately 2 years
Progression Free Survival (PFS) assessed by investigator per RECIST v1.1	PFS is defined as the time from randomization to the first documented disease progression (per RECIST v1.1 criteria) assessed by investigators or death due to any cause, whichever occurs first.	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
Peak Plasma Concentration (Cmax)	Derum drug concentrations in subjects at different time points after administration.	Up to approximately 2 years
Area under the plasma concentration versus time curve (AUC)	The definite integral of the concentration of AK138D1 in blood plasma as a function of time.	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Akeso
• Investigators: Principal Investigator: Fei Ma, Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Principal Investigator: Tong Liu, The Second Affiliated Hospital of Harbin Medical University; Principal Investigator: Ting Luo, West China Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 6, 2026
• Primary Completion (Estimated): June 6, 2028
• Study Completion (Estimated): September 14, 2030

Study Registration Dates

• First Submitted: April 24, 2026
• First Submitted That Met QC Criteria: April 24, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Breast cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: AK138D1-202

Drug and device information, study documents

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