A Phase II Study of AK146D1 Combined With AK112 in Advanced Breast Cancer

A Phase II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Efficacy of AK146D1 Combined With AK112 in Patients With Advanced Breast Cancer

This is a Phase II clinical study aimed at evaluating the safety, tolerability, antitumor efficacy, PK and immunogenicity of AK146D1 combined with AK112 in advanced breast cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Breast Cancer
• Intervention / Treatment: Drug: AK146D1 for injection; Drug: AK112 Injection

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ting Liu; Phone Number: +86(0760)8987 3999; Email: clinicaltrials@akesobio.com
• Study Contact Backup: Name: Zhimin Shao, Study Principal Investigator

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Fudan University Shanghai Cancer Center
      • Contact: Zhimin Shao; Phone Number: +86 021-64175590; Email: szmgcp2016@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Be able to understand and voluntarily sign the written informed consent form.
2. Aged of ≥ 18 years and ≤75 years.
3. ECOG PS 0 or 1.
4. The expected lifespan is ≥3 months.
5. Patients with histologically confirmed locally advanced, recurrent, or metastatic breast cancer who are not eligible for curative surgical resection; and who have histologically or cytologically confirmed HER2-negative disease.
6. At least one measurable lesion according to RECIST v1.1. Patients with only bone lesions or cutaneous lesions are not ineligible for enrollment.
7. Have sufficient organ function.
8. Females patients must not be pregnant at screening or have evidence of non-childbearing potential. Agree to use medically accepted methods of contraception.

Exclusion Criteria:

1. Patients had breast cancer amenable to curative treatment at study enrollment.
2. Concurrent other histopathological types confirmed by tumor histology or cytology.
3. Having other active malignancies within 3 years.
4. Currently participating in another interventional clinical study.
5. Presence of active metastases to the central nervous system. For patients with asymptomatic brain metastasis or stable symptoms after treatment can be included.
6. Prior treatment with any therapy targeting Trop-2 or Nectin-4, or any chemotherapy agent targeting topoisomerase I.
7. Receipt of systemic anti-tumor therapy (including chemotherapy, immunotherapy, biological agents, etc.) within 4 weeks prior to the first dose.
8. Toxicity of previous antineoplastic therapy has not resolved to NCI CTCAE 6.0 grade 1 or lower.
9. Patients with clinically significant cardiovascular or cerebrovascular diseases or risks.
10. Patients with active autoimmune diseases requiring systemic treatment within 2 years.
11. Receipt of systemic anti-infective therapy within 2 weeks prior to the first dose.
12. Known to be positive for HIV and other infections.
13. Previous history of severe hypersensitivity reactions.
14. Live attenuated vaccines were received within 4 weeks.
15. Patients with a history of mental illness and incapacitated or limited capacity.
16. Any disease or condition that, in the opinion of the investigator, would compromise patient safety or interfere with study assessments.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Participants in this group will receive AK146D1 combined with AK112 as i.v. infusion.	Drug: AK146D1 for injection; AK146D1 for injection is an anti-Trop2/Nectin4 bispecific antibody-drug conjugate.; Drug: AK112 Injection; AK112 Injection is a PD-1/VEGF bispecific antibody.
Experimental: Arm B; Participants in this group will receive AK146D1 as i.v. infusion.	Drug: AK146D1 for injection; AK146D1 for injection is an anti-Trop2/Nectin4 bispecific antibody-drug conjugate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs)	AEs refer to any untoward medical occurrence or deterioration of existing medical events after the participants sign the ICFs, whether or not considered related to the study treatment.	From the time of signing informed consent form through 30 days(for AEs) or 90 days(for SAEs) after the last dose of study drug.
Number of participants with dose limiting toxicities (DLTs)	DLTs are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug.	During the first 3 weeks of treatment in Safety Run-in Phase.
Objective Response Rate (ORR) assessed by investigator per RECIST v1.1	ORR is the proportion of participants with complete response(CR) or partial response(PR) , assessed based on RECIST v1.1.	Up to approximately 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) assessed by investigator per RECIST v1.1	PFS is defined as the time from the start of treatment until the first documentation of disease progression (based on RECIST Version 1.1) or death due to any cause, whichever occurs first.	Up to approximately 2 years.
Disease Control Rate (DCR) assessed per RECIST v1.1	DCR is defined as the proportion of participants with CR, PR, or SD, assessed based on RECIST v1.1.	Up to approximately 2 years.
Duration of response (DoR) assessed by the investigator per RECIST v1.1	DoR is defined as the duration from the first documentation of objective response to the first documented disease progression (based on RECIST Version 1.1) or death due to any cause, whichever occurs first.	Up to approximately 2 years.
Time to response (TTR) assessed by the investigator per RECIST v1.1	TTR is defined as the time to objective response based on RECIST v1.1.	Up to approximately 2 years.
Overall survival (OS)	OS is defined as the time from the first dose to death from any cause.	Up to approximately 2 years.
Serum PK concentration of AK146D1 and AK112	Serum PK concentration of AK146D1 and AK112 in participants after administration.	From pre-dose to the end of the last dose, an average of 6 months.
Anti-drug antibodies (ADA)	The number and percentage of participants with detectable anti-drug antibodies (ADA)	From pre-dose to 30 days post end of treatment.

Collaborators and Investigators

• Sponsor: Akeso

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): February 4, 2029

Study Registration Dates

• First Submitted: May 9, 2026
• First Submitted That Met QC Criteria: May 9, 2026
• First Posted (Actual): May 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Therapeutics; Drug Administration Routes; Drug Therapy; Injections
• Other Study ID Numbers: AK146D1-202

Drug and device information, study documents

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