AK112 or Placebo Plus Nab-Paclitaxel as First-line Treatment in Inoperable Locally Advanced/ Metastatic Triple-negative Breast Cancer

A Randomized, Controlled, Multi-center Phase III Clinical Study of AK112 Plus Nab-paclitaxel Versus Placebo Plus Nab-paclitaxel as First-line Treatment for Locally Advanced Unresectable or Metastatic Triple-negative Breast Cancer

This multicenter, randomized, double-blind study aims to assess the safety and efficacy of AK112 in combination with Nab-Paclitaxel, compared to a placebo plus Nab-Paclitaxel, as a first-line treatment for inoperable locally advanced or metastatic triple-negative breast cancer (TNBC).

Study Overview

• Status: Recruiting
• Conditions: Triple-Negative Breast Cancer (TNBC)
• Intervention / Treatment: Drug: AK112; Drug: Nab-paclitaxel; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 416
• Phase: Phase 3

Contacts and Locations

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

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Cancer Hospital Chinese Academy of Medical Sciences
    • Contact: Binghe Xu; Phone Number: 010-87788993; Email: xubinghe@medmail.com.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Voluntarily sign a written informed consent form.
2. Age at enrollment is ≥ 18 and ≤ 75 years, both males and females are eligible.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Life expectancy of ≥ 3 months.
5. Histologically confirmed unresectable locally advanced or metastatic breast cancer with negative status for ER, PR, and HER-2.
6. Subjects who have not received prior systemic treatment for advanced breast cancer are eligible for the study.
7. Suitable for monotherapy with taxane-based agents.
8. At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
9. Adequate organ function.

Exclusion Criteria:

1. Patients with locally recurrent disease who are eligible for surgery or radiotherapy.
2. History of other malignancies within the past 5 years.
3. Active autoimmune disease requiring systemic treatment within the past 2 years.
4. Pregnant or breastfeeding women.
5. Concurrent participation in another clinical trial, unless it is an observational or non-interventional study or in the follow-up phase of an interventional study.
6. Participants with clinically symptomatic pleural effusion, pericardial effusion, or ascites that require repeated drainage.
7. Participants with a history of immune deficiency; those who test positive for HIV antibodies; those currently using systemic corticosteroids or other immunosuppressive agents on a long-term basis.
8. Individuals with known active tuberculosis (TB), or those suspected of having active TB (who must undergo clinical evaluation for exclusion), and those with known active syphilis infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK112; AK112 Plus Nab-Paclitaxel	Drug: AK112; AK112 via intravenous (IV) infusion; Drug: Nab-paclitaxel; Nab-Paclitaxel 100mg/m2 via IV infusion on Days 1, 8, and 15 of each 28-day cycle
Placebo Comparator: Placebo; Placebo Plus Nab-Paclitaxel	Drug: Nab-paclitaxel; Nab-Paclitaxel 100mg/m2 via IV infusion on Days 1, 8, and 15 of each 28-day cycle; Drug: Placebo; Placebo via IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS assessed by IRRC	Progression-Free Survival (PFS) assessed by Independent Radiologic Review Committee (IRRC)	Up to approximately 2 years
OS	Overall survival (OS) is defined as the time from randomization to death due to any cause	Up to approximately 4 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
PFS assessed by investigator	Progression-free survival is defined as the time from randomization to the first documented PD per RECIST 1.1 based on assessments by investigator or death due to any cause, whichever occurs first.	Up to approximately 2 years
ORR assessed by IRRC or investigators	Objective Response Rate (ORR) is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experienced a CR or PR as assessed by IRRC or investigators based on RECIST 1.1 is presented.	Up to approximately 2 years
DCR assessed by IRRC or investigators	Disease control rate (DCR) is defined as the sum rate of CR, PR and Stable Disease (SD), as determined by IRRC or investigators using RECIST v1.1	Up to approximately 2 years
DoR assessed by IRRC or investigators	Duration of response (DoR) is defined as the time period from the date of initial CR or PR until the date of PD or death due to any cause, whichever occurs first.	Up to approximately 2 years
TTR assessed by IRRC or investigators	Time to response (TTR) is defined as the time to response based on RECIST v1.1.	Up to approximately 2 years
Adverse Events (AEs)	Incidence and severity of participants with adverse events	Up to approximately 2 years
Cmax and Cmin	AK112 serum drug concentrations in subjects at different time points after AK112 administration.	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Akeso

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: January 8, 2025
• First Submitted That Met QC Criteria: January 8, 2025
• First Posted (Actual): January 10, 2025

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Skin and Connective Tissue Diseases; Triple Negative Breast Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; 130-nm albumin-bound paclitaxel
• Other Study ID Numbers: AK112-308

Drug and device information, study documents

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