Akeso advances its IO2.0/ADC2.0 strategy with first patient dosed in Phase II trial of AK146D1 combined with ivonescimab for breast cancer
Executive summary: Akeso announced that the first patient has been dosed in a Phase II clinical study (AK146D1-202) of AK146D1, its TROP2/Nectin-4 bispecific ADC, combined with ivonescimab for breast cancer. This advances Akeso's IO2.0 + ADC2.0 strategy, expanding AK146D1's evaluation beyond NSCLC into breast cancer and testing a dual-mechanism approach linking ADC payload delivery with PD-1/VEGF blockade via ivonescimab.
Who is involved: Akeso, Inc. (9926.HK) is the sponsor; ivonescimab is Akeso's PD-1/VEGF bispecific antibody; the study is a Phase II trial in breast cancer patients.
Likely next: Further patient enrollment in the Phase II trial, interim data readouts on safety and efficacy, and potential expansion into additional cohorts or combination arms based on initial results.
Akeso dosed the first patient in a Phase II study evaluating AK146D1, its internally developed TROP2/Nectin-4 bispecific ADC, in combination with ivonescimab for breast cancer. This builds on prior clinical progress with AK146D1 in NSCLC and reflects Akeso's broader IO2.0 + ADC2.0 strategy to develop next-generation ADCs paired with immunomodulators. The trial aims to assess safety and efficacy in a heavily pretreated patient population, with potential implications for Akeso's pipeline and competitive positioning in ADC-based oncology therapies.
Timeline
- — Akeso Advances IO2.0 + ADC2.0 Strategy: First Patient Dosed in Phase II Study of TROP2/Nectin-4 Bispecific ADC (AK146D1) Combined with Ivonescimab in Breast Cancer (PR Newswire)
- — Akeso IO2.0 + ADC2.0 Strategy Makes Another Advancement: First Patient Dosed in Phase Ib/II Study of HER3 ADC (AK138D1) Combined with Ivonescimab in Lung Cancer (PR Newswire)
- — Akeso Doses First Patient in Phase II Study of Novel TROP2/Nectin-4 Bispecific ADC (AK146D1) in Combination with Ivonescimab for Advanced NSCLC (PR Newswire)
Analysis — what this means
Likely next events
- Interim safety and efficacy data from AK146D1-202 trial expected in H2 2027
- Potential presentation of updated data at major oncology congress (e.g., ESMO or SABCS) in late 2027
- Possible initiation of Phase III planning contingent on Phase II outcomes
Sectors affected
- Oncology biopharmaceuticals
- Antibody-drug conjugate (ADC) developers
- Breast cancer therapeutics
Regulatory implications
- Any regulatory filing (e.g., BLA) would require demonstration of clinically meaningful benefit over standard of care in refractory breast cancer
- CDMA or CDE alignment needed for China-based trial to support potential NMPA submission
Historical parallels
- Akeso's prior dosing of AK146D1 in NSCLC (July 20, 2026) followed similar Phase II design
- Enhertu (DS-8201a) approval in breast cancer based on TROP2-targeting ADC efficacy (2020)
- Trodelvy (sacituzumab govitecan) accelerated approval in breast cancer after Phase II success (2020)
Key entities
Sources
- Akeso Advances IO2.0 + ADC2.0 Strategy: First Patient Dosed in Phase II Study of TROP2/Nectin-4 Bispecific ADC (AK146D1) Combined with Ivonescimab in Breast Cancer — PR Newswire
- Akeso Doses First Patient in Phase II Study of Novel TROP2/Nectin-4 Bispecific ADC (AK146D1) in Combination with Ivonescimab for Advanced NSCLC — PR Newswire
- Akeso IO2.0 + ADC2.0 Strategy Makes Another Advancement: First Patient Dosed in Phase Ib/II Study of HER3 ADC (AK138D1) Combined with Ivonescimab in Lung Cancer — PR Newswire
Related cases
- Akeso’s 2026 interim results show record‑high drug sales and progress on its IO 2.0 strategy, advancing bispecific ADCs in oncology, immunology and Alzheimer’s
- Akeso's B7‑H3 ADC AK157D1 gains Phase I clearance, adding a third differentiated candidate to its oncology pipeline
- Henlius and Sandoz partner to co‑develop up to ten biosimilar mAb and ADC assets, aiming to accelerate global market access and revenue generation
- GlycoNex initiates first-in-human Phase I trial of its glycan-targeted ADC GNX1021 in Japan
- Akeso initiates first‑in‑human trial of its HER3‑targeted ADC combined with Ivonescimab in lung cancer, advancing its IO2.0+ADC2.0 pipeline
- Mabwell's ESMO 2026 oral presentation of clinical data for its Nectin-4-targeting ADC 9MW2821 highlights potential progress in triple-negative breast cancer therapy and could affect oncology investment sentiment