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

NCT07591090 | Not Yet Recruiting Phase 2

• 1 other identifier: AK146D1-202
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Breast Cancer

Outcome Measures

Primary Outcomes (3)

• 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.

• 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.

• 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 Outcomes (7)

• Progression Free Survival (PFS) assessed by investigator per RECIST v1.1

  Up to approximately 2 years.

• Disease Control Rate (DCR) assessed per RECIST v1.1

  Up to approximately 2 years.

• Duration of response (DoR) assessed by the investigator per RECIST v1.1

  Up to approximately 2 years.

• Time to response (TTR) assessed by the investigator per RECIST v1.1

  Up to approximately 2 years.

• Overall survival (OS)

  Up to approximately 2 years.

Study Arms (2)

Arm A

EXPERIMENTAL

Participants in this group will receive AK146D1 combined with AK112 as i.v. infusion.

Drug: AK146D1 for injection; Drug: AK112 Injection

Arm B

EXPERIMENTAL

Participants in this group will receive AK146D1 as i.v. infusion.

Drug: AK146D1 for injection

Interventions

AK146D1 for injection DRUG

AK146D1 for injection is an anti-Trop2/Nectin4 bispecific antibody-drug conjugate.

Arm A; Arm B

AK112 Injection DRUG

AK112 Injection is a PD-1/VEGF bispecific antibody.

Arm A

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able to understand and voluntarily sign the written informed consent form.
• Aged of ≥ 18 years and ≤75 years.
• ECOG PS 0 or 1.
• The expected lifespan is ≥3 months.
• 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.
• At least one measurable lesion according to RECIST v1.1. Patients with only bone lesions or cutaneous lesions are not ineligible for enrollment.
• Have sufficient organ function.
• Females patients must not be pregnant at screening or have evidence of non-childbearing potential. Agree to use medically accepted methods of contraception.

You may not qualify if:

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

Sponsors & Collaborators

• Akeso: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Location

MeSH Terms

Interventions

Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

Ting Liu

CONTACT

+86(0760)8987 3999; clinicaltrials@akesobio.com

Zhimin Shao, Study Principal Investigator

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2026
• First Posted: May 15, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): February 4, 2029
• Last Updated: May 15, 2026

Record last verified: 2026-04

Locations

CN (1)