Akeso opens recruiting for AK146D1-AK112 combo in HER2-negative breast cancer
The Phase 2 trial pairs Akeso's PD-1 bispecific with ivonescimab in advanced HER2-negative breast cancer, entering a field where PD-1-targeted therapy has failed 43% of the time at this same phase.
Executive Summary
- Akeso's Phase 2 study of its PD-1-targeted bispecific paired with ivonescimab in advanced breast cancer has begun recruiting patients, moving off its not-yet-recruiting status.
- The trial tests whether combining a checkpoint blocker with an anti-angiogenic bispecific can produce responses in HER2-negative advanced breast cancer, a setting where PD-1-targeted approaches have struggled to separate from chemotherapy alone.
- The combination enters a PD-1 x breast cancer field that already includes a dozen direct comparators in active testing, so any signal will be read against a landscape with a documented history of Phase 2 setbacks rather than judged as a novel mechanism.
- The enrollment target held flat and the status change tracks the trial's own design timeline, an unremarkable start that does not itself alter confidence in the eventual readout.
The status change
The trial, registered as NCT07591090, moved from Not yet recruiting to Recruiting on July 22, 2026, with a start date of July 17, 2026. It targets 200 patients with locally advanced, recurrent, or metastatic HER2-negative breast cancer who are not candidates for curative surgery, and requires at least one measurable lesion under RECIST v1.1. The study is open-label and non-randomized, with two experimental arms, and lists a primary completion date of September 1, 2027 and a full completion date of February 4, 2029. NCT07591090A Phase II Study of AK146D1 Combined With AK112 in Advanced Breast CancerNCT07591090
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
What it will measure
The trial carries three primary endpoints: adverse-event incidence, dose-limiting toxicities during a safety run-in, and objective response rate assessed by investigators under RECIST v1.1. That combination of a safety readout with an efficacy readout under one primary-endpoint umbrella means the trial is built to answer both whether the combination is tolerable and whether it produces tumor responses, rather than to support registration on its own; the study is not designated registrational. Secondary endpoints add disease control rate, duration of response, progression-free and overall survival, and pharmacokinetics for both drugs. NCT07591090A Phase II Study of AK146D1 Combined With AK112 in Advanced Breast CancerNCT07591090
The competitive field
PD-1-targeted therapy in breast cancer is a crowded and difficult setting: 48 active trials are currently studying PD-1 in breast cancer, and Phase 2 trials pairing PD-1 with breast cancer have terminated at a 43% rate, with 10 of 23 trials ending early and 15 distinct sponsors recording failures in this target-indication combination. Akeso's own PD-1 x VEGF-A bispecific approach is not a first-in-class entry; direct comparators sharing the PD-1 target and a checkpoint or bispecific mechanism class already run in breast and related -tumor trials, including Merck's pembrolizumab and Merck's sacituzumab tirumotecan, both currently in Phase 3 testing. Akeso's own cadonilimab, a separate PD-1 bispecific, is in Phase 3 testing in colon cancer, underscoring that the company is running the same modality across multiple tumor types rather than testing an isolated hypothesis in breast cancer alone.
The bar this readout must clear
Given a field where PD-1-directed approaches have not established a validated path to benefit in HER2-negative breast cancer and where a plurality of Phase 2 attempts have ended in termination, a response rate and durability signal that survives into randomized testing would be the result that distinguishes AK146D1 plus ivonescimab from the pattern of Phase 2 attrition already recorded in this target-indication pairing. Akeso's own track record shows an 85% completion rate across 41 checkpoint-receptor trials, which speaks to the sponsor's operational execution but says nothing about whether this particular combination will outperform the chemotherapy backbone or other checkpoint approaches already tested in this population.
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.