On July 27, 2026 Akeso, Inc. (9926.HK) ("Akeso" or the "Company") reported that the first patient has been dosed in a Phase Ib/II clinical study (AK138D1-201) evaluating its internally developed next-generation differentiated HER3 ADC, AK138D1, as monotherapy or in combination with ivonescimab (PD-1/VEGF bispecific antibody) for advanced non-small cell lung cancer (NSCLC).
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The study aims to evaluate the potential of Akeso’s IO2.0 + ADC2.0 regimen across multiple settings in advanced NSCLC, including: first-line treatment, treatment after EGFR-TKI resistance, and treatment after immuno-chemotherapy resistance.
HER3 expression is strongly linked to the development, progression, and treatment resistance in patients with NSCLC. Traditional HER3 ADCs have faced limitations in clinical use due to toxicity concerns, and none have been approved to date. Akeso designed the next-generation HER3 ADC, AK138D1, with an unique and innovative approach that minimizes uptake in normal tissues to reduce off-target toxicity and broaden the therapeutic window. This approach also prevents surface aggregation on tumor cells to improve deep and uniform tumor penetration, effectively overcoming the binding site barrier. Early clinical studies conducted in China and Australia have demonstrated that AK138D1 monotherapy delivers potent anti-tumor activity in patients with lung cancer, along with a favorable safety profile featuring low hematologic toxicity and no reported cases of interstitial lung disease (ILD).
Ivonescimab, a first-in-class PD-1/VEGF bispecific antibody, has shown strong clinical results compared to PD-1 inhibitor-based therapies across multiple Phase III studies. The combination of AK138D1 with ivonescimab is expected to further amplify ivonescimab’s immune-activating effects. This combination enables ivonescimab to exert synergistic anti-tumor activity with the next-generation HER3 ADC, potentially delivering superior clinical efficacy across various NSCLC subtypes while maintaining a favorable safety profile.
Leveraging its technological leadership in bispecific and multi-specific antibodies, Akeso is systematically building a comprehensive global IO2.0 + ADC2.0 therapeutic matrix.
In the immuno-oncology field, Akeso has two approved bispecific antibodies for cancer treatment. The Company is actively evaluating ivonescimab and cadonilimab in combination with the Company’s proprietary next-generation ADC candidates. Increasingly, global partners recognize both ivonescimab and cadonilimab as preferred agents for combination regimens and breakthrough therapy explorations across a wide spectrum of tumor types.
In the ADC space, Akeso has built a differentiated pipeline of next-generation candidates, including AK146D1 and AK138D1, both of which have entered into Phase II clinical studies, and AK157D1 and AK158D1 (a bispecific ADC), both of which will soon enter clinical studies.
Currently, multiple Phase II clinical studies are underway evaluating ivonescimab and cadonilimab in combination with AK138D1, AK146D1, and other assets. These combination studies from Akeso’s own approved therapies and pipelines continue to drive global treatment paradigms upgrades for major malignancies, including lung cancer and breast cancer.
About AK138D1
Injectable AK138D1 is a HER3-targeted antibody-drug conjugate (ADC), with a fully humanized anti-HER3 IgG1 antibody, patritumab. It is conjugated to the topoisomerase I inhibitor DXd through a cleavable linker, MC-AAA (maleimide-alanine-alanine-alanine). After binding to HER3 on tumor cells, the ADC is internalized into the tumor cells, where the linker is cleaved, releasing the membrane-permeable DXd. This leads to DNA damage and subsequent cell apoptosis. Early study results have shown that AK138D1 possesses potent biological activity and a favorable safety profile. A phase II clinical trial is currently ongoing to investigate AK138D1 combined with cadonilimab and ivonescimab in patients with solid tumors. This regimen is a critical part of Akeso’s IO2.0 + ADC 2.0 combination approach.
(Press release, Akeso Biopharma, JUL 27, 2026, View Source;adc2-0-strategy-makes-another-advancement-first-patient-dosed-in-phase-ibii-study-of-her3-adc-ak138d1-combined-with-ivonescimab-in-lung-cancer-302835843.html [SID1234669436])