Logo Image
News|Articles|August 10, 2026

Akeso Doses First Patient in Phase 2 Trial of Bispecific ADC AK146D1 Plus Ivonescimab in Breast Cancer

Listen
0:00 / 0:00

Key Takeaways

  • Akeso dosed the first patient in phase 2 AK146D1-202 evaluating AK146D1 plus ivonescimab as first-line therapy for HR-positive/HER2-negative breast cancer and TNBC.
  • Dual targeting of TROP2 and Nectin-4 with a cleavable MC-AAA linker–DXd payload is intended to enhance tumor selectivity and antitumor potency with manageable toxicity.
SHOW MORE

Akeso is pairing a next-gen bispecific ADC with its PD-1/VEGF antibody, ivonescimab, in a first-line push against hard-to-treat breast cancer.

Hong Kong-based Akeso has dosed the first patient in a phase 2 trial (AK146D1-202) evaluating its TROP2/Nectin-4 bispecific antibody-drug conjugate (bsADC), AK146D1, in combination with its programmed cell death protein 1 (PD-1)/vascular endothelial growth factor (VEGF) bispecific antibody, ivonescimab, for advanced breast cancer, the company announced August 10, 2026.¹ The study is part of Akeso's IO2.0 + ADC2.0 strategy and will focus on first-line treatment of hormone receptor (HR)-positive/HER2-negative breast cancer and triple-negative breast cancer (TNBC).¹

Key facts

  • Drugs: AK146D1 (bsADC) plus ivonescimab (Akeso)
  • Class: TROP2/Nectin-4 bispecific ADC + PD-1/VEGF bispecific antibody
  • Indication studied: Advanced breast cancer (HR+/HER2- and TNBC, first-line)
  • Trial: AK146D1-202; phase 2
  • Milestone: First patient dosed, announced Aug. 10, 2026
  • Strategy context: Part of Akeso's IO2.0 + ADC2.0 combination approach
  • Related program: Phase 3 ivonescimab-based TNBC combination ongoing
  • Related program: AK146D1 also in phase 2 with cadonilimab + ivonescimab (solid tumors)
  • Pipeline scale: 50+ assets; 27 in clinical trials; 8 commercial-stage
  • Geography: Hong Kong-based (Akeso); global pipeline

Why is this combination being tested in breast cancer?

Breast cancer is the second most common malignancy worldwide, with approximately 2.3 million new cases diagnosed annually.¹ Despite advances in molecular subtype-guided precision medicine, including targeted therapies, immunotherapies, and ADCs, immuno-oncology approaches remain limited in programmed cell death ligand 1 (PD-L1)-negative patients and those who develop resistance to anti-PD-1 therapy, while ADC safety constraints restrict both therapeutic benefit and the number of treatment lines patients can receive. Akeso said combining AK146D1 with ivonescimab has the potential to improve clinical efficacy while maintaining a manageable safety profile, potentially expanding treatment options for patients with advanced breast cancer.¹

What is known about the 2 therapies being combined?

AK146D1 is a bispecific ADC that simultaneously targets Trop2 and Nectin4, conjugated via a cleavable maleimide-alanine-alanine-alanine (MC-AAA) linker to the topoisomerase I inhibitor DXd, and has demonstrated potent antitumor activity and a favorable safety profile in early clinical studies.¹ Ivonescimab is a first-in-class bispecific antibody that cooperatively binds PD-1 and VEGF and has previously demonstrated superior efficacy over pembrolizumab in the phase 3 HARMONi-2 trial in non-small cell lung cancer, one of several phase 3 studies supporting its clinical profile.² Building on encouraging phase 2 data for ivonescimab in breast cancer, a separate phase 3 study evaluating an ivonescimab-based combination as first-line treatment for TNBC is also currently underway.¹

How does this fit into Akeso's broader pipeline?

Akeso has 2 approved bispecific antibodies for cancer treatment, cadonilimab (PD-1/cytotoxic T lymphocyte associated antigen 4) and ivonescimab (PD-1/VEGF)—both approved in China—and is evaluating both in combination with its next-generation ADC candidates, which include AK146D1, AK138D1, AK157D1, and the bispecific ADC AK158D1.¹,³ AK146D1 itself is Akeso's first bispecific ADC to enter clinical trials, having received clearance from FDA, Australia's Therapeutic Goods Administration, and China's National Medical Products Administration to begin testing.³

The company is separately conducting a phase 1b/2 study combining its HER3 ADC candidate, AK138D1, with ivonescimab, and a phase 2 study of AK146D1 combined with both cadonilimab and ivonescimab across multiple solid tumors.¹ Of Akeso's more than 50 pipeline assets spanning cancer, autoimmune disease, and other therapeutic areas, 27 have advanced into clinical trials and 8 have reached the commercial stage.¹

What are the limitations?

This is a first-patient-dosed milestone in an early-stage phase 2 study, and no efficacy or safety data for the AK146D1-ivonescimab combination in breast cancer have yet been reported. The company did not specify enrollment targets or an expected data readout timeline in this announcement.

References

  1. Akeso. 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. Press release. Published August 10, 2026. Accessed August 10, 2026. https://www.akesobio.com/en/media/akeso-news/260810/
  2. Xiong A, Wang L, Chen J, et al. Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China. Lancet. 2025;405(10481):839-849. doi:10.1016/S0140-6736(24)02722-3
  3. Akeso. Akeso's first bispecific ADC (Trop2/Nectin4 ADC) enters clinical trials, strengthening leadership in ‘IO+ADC’ 2.0 strategy. Press release. Published July 3, 2025. Accessed August 10, 2026. https://www.akesobio.com/en/media/akeso-news/250703/

Related Content