Akeso, Inc. has unveiled updated Phase II clinical data for its investigational PD-1/VEGF bispecific antibody ivonescimab, showing an 80 percent objective response rate (ORR) and 100 percent disease control rate (DCR) when combined with chemotherapy as a first-line treatment for triple-negative breast cancer (TNBC). Presented at the 2025 ESMO Immuno-Oncology Congress in London, the findings reflect a longer follow-up of 22.1 months, extending previously reported results and reinforcing the rationale for the drug’s ongoing Phase III evaluation under the HARMONi-BC1 study. Ivonescimab had earlier secured Breakthrough Therapy Designation in China based on its novel dual-targeting mechanism and early clinical promise.

What the new data signal about the promise and limits of PD-1/VEGF bispecifics

The most striking aspect of the updated data is the consistency of efficacy across PD-L1 subgroups, including patients with lower PD-L1 expression. In immuno-oncology, this is not a trivial finding. Immune checkpoint inhibitors such as pembrolizumab or atezolizumab have historically shown more selective efficacy in PD-L1 positive TNBC populations, particularly those with a combined positive score (CPS) of 10 or above. Ivonescimab’s performance, by contrast, remained stable across CPS<10, CPS≥10, and CPS≥1 cohorts.

Among patients with CPS≥10, the ORR reached 83.3 percent and mPFS was 15.9 months. In the CPS<10 group, response remained robust at 79.3 percent, with a median progression-free survival of 13.04 months. While the overall survival (OS) data remain immature, the 12-month PFS rate of 56.3 percent in the overall population suggests meaningful disease control for a hard-to-treat subtype.

From a mechanistic standpoint, the bispecific approach offers a dual benefit. By simultaneously engaging the PD-1 axis to release T-cell inhibition and blocking VEGF-driven angiogenesis, ivonescimab may be converting immunologically “cold” tumors into “hotter,” more responsive phenotypes. That potential to modulate the tumor microenvironment could be particularly impactful in TNBC, which often lacks hormone receptors and HER2 expression, leaving immunotherapy as a key remaining lever.

How ivonescimab is positioned differently from current PD-1-based regimens

Ivonescimab is not the first drug to combine immunotherapy and chemotherapy in TNBC, but its bispecific format distinguishes it from earlier checkpoint regimens. Pembrolizumab in combination with chemotherapy was approved based on KEYNOTE-355, yet the benefit was largely confined to CPS≥10 patients. In contrast, the efficacy of ivonescimab in lower PD-L1 expression groups broadens the potential population that may benefit.

What remains to be seen is whether this approach holds up against existing standards when tested head-to-head. The HARMONi-BC1 trial is still in progress, and without direct comparative data, clinicians will likely continue to rely on known regimens. However, the ORR of 80 percent reported here exceeds what has been typically observed with monotherapy PD-1 inhibitors, and early tolerability signals appear favorable.

Importantly, there were no treatment-related adverse events leading to discontinuation or death in this Phase II cohort. Most reported adverse events were grade 1 or 2, which contrasts positively with the higher toxicity seen in dual checkpoint regimens such as PD-1 plus CTLA-4 combinations. Clinicians tracking this space are likely to view ivonescimab as a potentially safer alternative with broad efficacy.

What this reveals about Akeso’s strategy for regulatory and commercial differentiation

Akeso is deploying a deliberate pipeline strategy focused on bispecific antibodies and leveraging China’s regulatory pathways to accelerate progress. The Breakthrough Therapy Designation granted by China’s Center for Drug Evaluation (CDE) positions the company to pursue conditional approval if Phase III data aligns with the Phase II trends. This regulatory agility could allow Akeso to enter the Chinese market faster than competitors pursuing standard global registration timelines.

China’s regulatory environment has become increasingly receptive to innovative mechanisms, and ivonescimab may serve as a proof-of-concept that domestic innovation can challenge Western-origin checkpoint therapies. Should Akeso succeed in commercializing ivonescimab domestically, the next hurdle will be demonstrating its relevance to regulators such as the United States Food and Drug Administration and the European Medicines Agency. For that, multi-regional clinical trials will be essential.

While Akeso has a strong manufacturing platform, including its proprietary ACE Platform and Tetrabody bispecific technology, international scalability and supply chain resilience will come under scrutiny. The ability to produce consistent, GMP-compliant product batches at commercial scale remains a gating factor for any bispecific therapeutic entering the global oncology market.

Why TNBC remains a proving ground for next-generation immunotherapies

Triple-negative breast cancer continues to represent one of the most aggressive and treatment-resistant forms of breast cancer. With limited targeted therapies available, innovation in this space often defines broader immuno-oncology progress. PD-1 checkpoint inhibitors have made partial inroads, but the need for more durable, widespread responses has left the door open for alternative strategies.

Bispecific antibodies like ivonescimab offer the opportunity to move beyond monotherapy and binary combinations. By integrating immune checkpoint modulation with antiangiogenic activity, Akeso is attempting to deliver a multi-modal response in a single molecule. Whether this proves superior to sequential or combination therapy with separate agents remains to be proven, but the convenience and potential cost advantages are worth monitoring.

From a biomarker perspective, Akeso’s data suggests that PD-L1 CPS alone may not be sufficient to predict response to ivonescimab. If validated in larger cohorts, this could prompt a re-evaluation of biomarker stratification strategies in TNBC. It may also introduce new questions around resistance mechanisms, durability of response, and relapse biology, all of which remain underexplored in the context of bispecifics.

What could go wrong and where uncertainty remains

Despite the optimism, there are still clear limitations to the current dataset. The sample size is modest at 36 patients, and the single-arm design limits interpretability. Moreover, OS data are not yet mature, and mPFS as a surrogate endpoint remains imperfect in the TNBC setting. There is also limited visibility into the drug’s activity in patients with prior exposure to immunotherapy or VEGF inhibitors, which may become more common in future treatment sequences.

Manufacturing and cost are also non-trivial concerns. Bispecific antibodies are more complex to produce, and any scale-up will require investment in quality control, process validation, and global distribution logistics. For a drug aiming to compete in front-line TNBC—a relatively high-volume indication—these aspects could become operational bottlenecks.

Additionally, market access outside China may hinge on comparative pricing, head-to-head data, and real-world performance. Without partnerships or licensing agreements in major global markets, Akeso could struggle to establish commercial presence even if regulatory approval is achieved.

  Akeso, bispecific antibody, checkpoint inhibitor, Chinese biotech, ESMO IO 2025, first-line oncology, HARMONi-BC1, immuno-oncology, Ivonescimab, PD-1, Phase II, TNBC, triple-negative breast cancer, VEGF