Hong Kong, July 27, 2026
Akeso, Inc. has announced that the first patient has been dosed in the Phase Ib/II clinical study (AK138D1-201) evaluating its next-generation HER3 antibody-drug conjugate (ADC), AK138D1, as both a monotherapy and in combination with ivonescimab, the company’s first-in-class PD-1/VEGF bispecific antibody, for the treatment of advanced non-small cell lung cancer (NSCLC). The milestone represents another significant advancement in Akeso’s IO2.0 + ADC2.0 strategy, designed to integrate innovative immuno-oncology and next-generation ADC technologies to improve treatment outcomes for patients with difficult-to-treat cancers. The study will evaluate the combination therapy across multiple advanced NSCLC settings, including first-line treatment, patients with EGFR-TKI resistance, and individuals whose disease has progressed following immuno-chemotherapy, reinforcing Akeso’s commitment to expanding precision oncology solutions through differentiated biologic therapies.
Phase Ib/II Study Evaluates Next-Generation HER3 ADC Strategy
The newly initiated AK138D1-201 Phase Ib/II clinical trial has been designed to assess the safety, tolerability, and preliminary antitumor activity of AK138D1 alone and in combination with ivonescimab in patients with advanced NSCLC. HER3 has emerged as an important therapeutic target due to its strong association with tumor progression, disease recurrence, and treatment resistance in lung cancer. Unlike earlier HER3-targeted ADCs that have faced challenges related to toxicity, AK138D1 has been engineered using an innovative molecular design that minimizes uptake in normal tissues, reduces off-target toxicity, broadens the therapeutic window, and enhances deep tumor penetration. Early clinical studies conducted in China and Australia demonstrated encouraging antitumor activity, together with a favorable safety profile characterized by low hematologic toxicity and no reported cases of interstitial lung disease (ILD), supporting continued global clinical development.
Ivonescimab Combination Strengthens IO2.0 + ADC2.0 Platform
The combination of AK138D1 with ivonescimab represents a key component of Akeso’s IO2.0 + ADC2.0 therapeutic strategy, which integrates bispecific antibodies and next-generation ADCs to maximize antitumor efficacy while maintaining favorable safety. Ivonescimab, a PD-1/VEGF bispecific antibody, has already demonstrated strong clinical performance across multiple Phase III clinical studies, outperforming conventional PD-1 inhibitor-based therapies in several oncology settings. By combining the immune-activating effects of ivonescimab with the targeted cytotoxic activity of AK138D1, Akeso aims to generate synergistic responses across diverse NSCLC subtypes, including patients with resistance to current standard-of-care therapies. The study further strengthens Akeso’s expanding immuno-oncology portfolio and supports the company’s vision of establishing next-generation combination regimens capable of addressing significant unmet medical needs in lung cancer treatment.
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Expanding a Global Pipeline of Innovative Oncology Therapies
The initiation of this clinical study further reinforces Akeso’s position as a leading biopharmaceutical innovator with one of the industry’s most comprehensive pipelines of bispecific antibodies, multi-specific antibodies, and antibody-drug conjugates. In addition to AK138D1, the company continues advancing multiple next-generation ADC candidates, including AK146D1, AK157D1, and AK158D1, while evaluating combination strategies involving both ivonescimab and cadonilimab across multiple solid tumors. Backed by its proprietary Tetrabody antibody platform, AI-powered drug discovery technologies, and Dual-Shield ADC platform, Akeso is building an integrated oncology ecosystem focused on delivering first-in-class and best-in-class biologic therapies. As additional clinical data emerge from ongoing Phase II and combination studies, the company’s IO2.0 + ADC2.0 strategy is expected to accelerate innovation in precision oncology while supporting the development of more effective treatment options for patients with lung cancer, breast cancer, and other advanced malignancies.
Source: Akeso press release
