Hong Kong, China, August 9, 2026
Akeso, Inc. has announced the first patient dosing in a Phase II clinical study evaluating AK146D1, the company’s internally developed TROP2/Nectin-4 bispecific antibody-drug conjugate (bsADC), in combination with ivonescimab, a PD-1/VEGF bispecific antibody, for patients with advanced breast cancer. The study, designated AK146D1-202, is designed to investigate Akeso’s “IO 2.0 + ADC 2.0” treatment strategy, with particular attention to first-line treatment of HR+/HER2- breast cancer and triple-negative breast cancer (TNBC). The clinical milestone expands Akeso’s efforts to develop multi-targeted cancer therapies that combine immuno-oncology and next-generation ADC technologies.
AK146D1 Enters Phase II Development
AK146D1 is a next-generation bispecific ADC designed to simultaneously target TROP2 and Nectin-4, two clinically relevant targets in cancer therapy. The candidate combines a bispecific antibody with a cleavable MC-AAA linker connected to DXd, a topoisomerase I inhibitor, creating a targeted drug-delivery approach intended to selectively deliver the cytotoxic payload to tumor cells. According to Akeso, early research has demonstrated potent biological activity and a favorable safety profile for AK146D1. The company is also evaluating AK146D1 in another Phase II study in combination with cadonilimab and ivonescimab across multiple solid tumors. The latest Phase II trial in advanced breast cancer therefore represents another clinical application of Akeso’s broader strategy to combine next-generation ADCs with immune-based therapies.
The company is focusing the AK146D1-202 study on advanced breast cancer, including HR+/HER2- disease and TNBC, areas where treatment resistance, tumor heterogeneity, and limitations associated with existing therapies continue to create significant clinical challenges.
Ivonescimab and ADC Combination Targets Unmet Needs
Advertisement
Ivonescimab is a PD-1/VEGF bispecific antibody that Akeso is developing as a key component of its immuno-oncology pipeline. The company states that ivonescimab has demonstrated clinical results compared with PD-1 inhibitor-based therapies across multiple Phase III studies. Akeso is also advancing an ivonescimab-based Phase III study as a first-line treatment for TNBC following encouraging Phase II data in breast cancer.
The combination of ivonescimab and AK146D1 is intended to bring together complementary mechanisms of action. According to Akeso, the approach could potentially enhance antitumor activity while maintaining a manageable safety profile. However, the combination remains investigational, and its clinical efficacy and safety will need to be established through ongoing clinical development. Breast cancer remains one of the most common cancers worldwide, with approximately 2.3 million new cases diagnosed annually, according to the company. Although molecularly guided therapies, immunotherapies, and ADCs have improved outcomes for some patients, substantial unmet needs remain. These include treatment resistance, limited effective options for certain patient populations, tumor heterogeneity, and safety considerations that can restrict the use of ADC therapies.
Akeso Advances “IO 2.0 + ADC 2.0” Strategy
Akeso’s “IO 2.0 + ADC 2.0” strategy is designed to combine multi-target and multi-mechanism therapies to potentially improve treatment outcomes across major cancers. The company is developing a pipeline of next-generation ADC candidates, including AK146D1, AK138D1, AK157D1, and AK158D1, with the goal of addressing limitations associated with earlier ADC technologies. The company is also evaluating AK138D1, a next-generation HER3 ADC, in combination with ivonescimab in a Phase Ib/II study. These programs reflect Akeso’s broader effort to develop combination regimens across different tumor types, treatment lines, and molecular subtypes.
The initiation of the AK146D1 Phase II study marks an important clinical development milestone for Akeso’s breast cancer pipeline. By combining a TROP2/Nectin-4 bispecific ADC with PD-1/VEGF-targeted immunotherapy, the company is pursuing a multi-mechanistic approach intended to address the complex biology and treatment challenges associated with advanced breast cancer.
Source: Akeso press release
