Akeso Doses First Patient in HER3 ADC Combo Trial
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Akeso said July 27, 2026 that the first patient was dosed in Phase Ib/II AK138D1-201 of HER3 ADC AK138D1 ± ivonescimab in advanced NSCLC.
Akeso AK138D1 HER3 ADC ivonescimab NSCLC dosing has begun in study AK138D1-201. On July 27, 2026, Akeso said the first patient received the next-generation HER3 antibody-drug conjugate alone or with the PD-1/VEGF bispecific ivonescimab in advanced non-small cell lung cancer.
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Key Takeaways
- First patient dosed in Phase Ib/II study AK138D1-201 on or before the July 27, 2026 announcement.
- AK138D1 is Akeso's HER3 ADC using patritumab and a DXd payload via an MC-AAA linker.
- Arms include monotherapy and combination with ivonescimab across multiple NSCLC settings.
- Early China/Australia monotherapy work cited low hematologic toxicity and no reported ILD.
AK138D1-201 at a glance
| Field | Detail |
|---|---|
| Candidate | AK138D1 (HER3 ADC) |
| Combo partner | Ivonescimab (PD-1/VEGF bispecific) |
| Sponsor | Akeso, Inc. (9926.HK) |
| Study | Phase Ib/II AK138D1-201 |
| Indication | Advanced NSCLC (1L; post-EGFR-TKI; post-IO-chemo) |
| Payload / Ab | DXd topoisomerase I inhibitor; patritumab IgG1 |
| Announcement | First patient dosed — July 27, 2026 PR Newswire |
What milestone did Akeso announce?
Akeso said the first patient has been dosed in Phase Ib/II study AK138D1-201 evaluating AK138D1 as monotherapy or combined with ivonescimab for advanced NSCLC. The program is positioned to test Akeso's "IO2.0 + ADC2.0" regimen in first-line disease, after EGFR-TKI resistance, and after immuno-chemotherapy resistance.
Source: Akeso's July 27 PR Newswire first-patient dosing release.
What is AK138D1's design?
Akeso described AK138D1 as a HER3-targeted ADC with a fully humanized anti-HER3 IgG1 antibody (patritumab) conjugated to the topoisomerase I inhibitor DXd through a cleavable MC-AAA linker. After HER3 binding and internalization, linker cleavage releases membrane-permeable DXd, causing DNA damage and apoptosis.
The company said the next-generation design aims to reduce normal-tissue uptake and surface aggregation to widen the therapeutic window. Early clinical studies in China and Australia were described as showing potent antitumor activity with low hematologic toxicity and no reported interstitial lung disease — claims that still need peer-reviewed confirmation and larger datasets.
Why combine with ivonescimab?
Ivonescimab is Akeso's PD-1/VEGF bispecific antibody. Akeso said combination with AK138D1 is expected to amplify immune activation while the ADC attacks HER3-expressing NSCLC clones. HER3 expression is linked to NSCLC progression and treatment resistance; no HER3 ADC is approved to date, per the company's framing.
- Settings: first-line, post-EGFR-TKI, post-IO-chemotherapy
- Related ADC pipeline: AK146D1 also in Phase II; AK157D1 and bispecific ADC AK158D1 nearing clinic
- Multiple Phase II combos of ivonescimab/cadonilimab with AK138D1 and AK146D1 underway
For broader China oncology trial pace, see NovaPharma's China trial-speed analysis and recent ADC approvals such as iza-bren in ESCC.
What should trial watchers track?
Watch dose-limiting toxicities for the ADC plus VEGF/PD-1 blockade, especially bleeding, hypertension, and ILD signals historically associated with some DXd conjugates. Registry postings on ClinicalTrials.gov should clarify cohort sizes and biomarker gating on HER3 expression.
A first-patient dose is an operational milestone, not efficacy proof. Cross-trial comparisons with other HER3 ADCs will require ORR, DoR, and grade ≥3 AE tables from this combination study.
What remains unproven?
No efficacy percentages from AK138D1-201 were released. The "no reported ILD" claim refers to earlier monotherapy experience and may not hold in larger or combination cohorts. Regulatory timelines for a China or global filing were not provided.
Related NovaPharma coverage
- Hansoh Ris-Rez Hits OS Goal in China SCLC Trial
- NMPA Approves Iza-bren for ESCC in China
- China trial speed draws oncology go-East plans
Frequently Asked Questions
What study just dosed its first patient?
Akeso said the first patient was dosed in Phase Ib/II study AK138D1-201 of HER3 ADC AK138D1 alone or with ivonescimab in advanced NSCLC, announced July 27, 2026.
What is AK138D1?
AK138D1 is Akeso's HER3-targeted antibody-drug conjugate using patritumab conjugated to a DXd topoisomerase I inhibitor via an MC-AAA linker.
Is a HER3 ADC already approved?
Akeso stated that traditional HER3 ADCs have faced toxicity limitations and that none have been approved to date. AK138D1 remains investigational.
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