HONG KONG, June 15, 2026
Akeso, Inc. has announced the enrollment of the first patient in the Phase Ib/II AK138D1-202 clinical trial, evaluating its next-generation HER3-targeted antibody-drug conjugate (ADC) AK138D1 as both a monotherapy and in combination with ivonescimab for the treatment of advanced breast cancer. The milestone marks another important step in Akeso’s strategy to advance its proprietary “IO2.0 + ADC2.0” oncology platform, which combines next-generation immunotherapy with innovative antibody-drug conjugate technologies. The study focuses on two of the largest and most challenging breast cancer populations—hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer and triple-negative breast cancer (TNBC)—where significant unmet medical needs remain despite advances in targeted therapies and immunotherapy. By leveraging the strengths of both ADC and immuno-oncology technologies, Akeso aims to deliver more effective and safer treatment options for patients with advanced disease.
Next-Generation HER3 ADC Designed to Overcome Traditional Limitations
HER3 is widely expressed across multiple solid tumors, including breast, lung, ovarian, gastric, pancreatic and colorectal cancers, making it an attractive therapeutic target. While previous HER3-targeted ADCs have demonstrated encouraging anti-tumor activity, their clinical utility has often been limited by dose-limiting toxicities and narrow therapeutic windows. Akeso’s AK138D1 has been specifically engineered to address these challenges through a differentiated molecular design that reduces uptake in normal tissues, helping minimize off-target toxicity while improving therapeutic selectivity. The company also reports that the ADC’s structure prevents excessive clustering on tumor cell surfaces, allowing deeper penetration into tumor tissue and more uniform drug distribution.
Early-stage clinical studies conducted in China and Australia have shown that AK138D1 delivers strong anti-tumor activity alongside a favorable safety profile, including notably low hematologic toxicity and no reported cases of interstitial lung disease (ILD), one of the key safety concerns associated with several ADC therapies. These findings position AK138D1 as a potentially important next-generation ADC candidate capable of supporting a broad range of combination treatment strategies.
Targeting Major Breast Cancer Subtypes With Significant Unmet Need
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The AK138D1-202 study is designed to evaluate treatment across multiple lines of therapy, enrolling patients ranging from treatment-naïve individuals to heavily pretreated populations. The trial includes patients with varying levels of PD-L1 expression, reflecting the diverse biology of advanced breast cancer. HR+/HER2- breast cancer accounts for approximately 65% of all breast cancer cases, while TNBC represents 10–20% of diagnoses and remains one of the most aggressive and difficult-to-treat breast cancer subtypes. Despite recent therapeutic advances, many patients eventually experience disease progression and require additional treatment options.
Early clinical data from AK138D1 studies have already demonstrated promising efficacy in breast cancer settings, providing a strong rationale for further exploration in combination regimens. At the same time, Akeso continues to advance ivonescimab-based therapies, including an ongoing Phase III first-line TNBC study, further expanding its oncology development portfolio.
IO2.0 Plus ADC2.0 Strategy Strengthens Akeso’s Oncology Leadership
The combination of AK138D1 and ivonescimab represents a cornerstone of Akeso’s vision for the future of cancer treatment. As IO plus ADC combinations emerge as one of the most active areas of oncology research globally, Akeso is leveraging its expertise in bispecific antibodies, multispecific biologics and advanced ADC platforms to create differentiated therapeutic approaches. The company is currently the only biotechnology firm worldwide with two approved oncology bispecific antibodies, reinforcing its leadership position in next-generation immunotherapy.
Through programs such as AK138D1 and its broader ADC pipeline, Akeso aims to address toxicity-related challenges that have limited first-generation ADCs while improving efficacy and treatment durability. With the first patient now enrolled, the AK138D1-202 study represents a significant milestone in advancing the company’s IO2.0 + ADC2.0 strategy and could help establish a new treatment paradigm for patients with advanced breast cancer who continue to face limited long-term therapeutic options.
Source: Akeso press release
