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Trastuzumab botidotin is a HER2-targeted ADC composed of a cytotoxic drug (Duostatin-5, anti-microtubule agent) with site-specific conjugation to trastuzumab via a stable protease-cleavable valine-citrulline linker. The unique linker is stable in plasma and selectively cleaved by lysosomal cathepsin B that is up-regulated in cancer cells.

In this study, a total of 365 patients with HER2+ unresectable or metastatic BC who had received at least one prior anti-HER2 therapy were randomized (1:1) to receive trastuzumab botidotin or T-DM1. 53% of patients had received ≥2 lines of anti-HER2 therapy, 61% of patients had HER2 Immunohistochemistry (IHC) 3+, and 60% of patients had been treated with TKIs, particularly pyrotinib (56%). As of April 26, 2025, median follow-up was 14.9 months.

Median PFS was significantly longer in trastuzumab botidotin than in T-DM1 (11.1 months vs 4.4 months; HR: 0.39, 95% CI, 0.30-0.51, p<0.0001). PFS benefit with trastuzumab botidotin was consistently observed regardless of prior lines of anti-HER2 therapy (HR 0.36, 95% CI, 0.25-0.53, for 1 prior line; HR 0.39, 95% CI, 0.28-0.56, for ≥2 prior lines).

ORR by blinded independent central review (BICR) was 76.9% vs 53.0%.

A trend toward benefit in OS was observed in trastuzumab botidotin (HR 0.62; 95% CI, 0.38-1.03).

Grade ≥3 treatment emergent adverse events (TEAEs) occurred in 69.8% of patients in trastuzumab botidotin and 63.7% in T-DM1. The most common TEAEs associated with dose reduction were ocular AEs for trastuzumab botidotin, and were platelet count decreased for trastuzumab emtansine. Only two patients permanently discontinued trastuzumab botidotin due to TEAE. No on-treatment deaths were observed in trastuzumab botidotin, compared with 1.6% in T-DM1, all of which were considered unrelated to treatment.

As a conclusion, this second head-to-head trial comparing T-DM1 with other anti-HER2 regimens demonstrated that trastuzumab botidotin statistically improved PFS with an ORR of 76.9% vs 53.0%. PFS benefit with trastuzumab botidotin was consistently observed regardless of prior lines of anti-HER2 therapy. Ocular AEs were also manageable.

“Professor Xichun Hu, National Lead Principal Investigator from Fudan University Shanghai Cancer Center:”Trastuzumab botidotin effectively balances safety and efficacy through its unique molecular design, reducing the incidence of interstitial lung disease and hematologic toxicity. According to research data, trastuzumab botidotin demonstrated significant survival benefits in the pivotal Phase III trial, with an overall manageable safety profile, providing a new important treatment option for pretreated HER2+ BC patients. These positive results also offer robust evidence-based support for personalized treatment and updates to clinical practice guidelines.”

About  Trastuzumab botidotin

Trastuzumab botidotin is a differentiated HER2 ADC to treat advanced HER2+ solid tumors. As an innovative HER2 ADC developed by the Company, it conjugates a novel, monomethyl auristatin F (MMAF) derivative (a highly cytotoxic tubulin inhibitor, Duo-5) via a stable, enzyme-cleavable linker to a HER2 monoclonal antibody with a DAR of 2. Trastuzumab botidotin specifically binds to HER2 on the surface of tumor cells and is internalized by tumor cells, releasing the toxin molecule Duo-5 inside the cell. Duo-5 induces tumor cell cycle arrest in the G2/M phase, leading to tumor cell apoptosis. After targeting HER2, trastuzumab botidotin can also inhibit the HER2 signaling pathway; it has antibody-dependent cell-mediated cytotoxicity (ADCC) activity.

Based on the results of a multi-center, randomized, open-label, controlled, Phase 3 KL166-III-06 study, trastuzumab botidotin was approved for marketing by the NMPA in for adult patients with unresectable or metastatic HER2 positive BC who have received one or more prior anti-HER2 therapy. At a pre-specified interim analysis, trastuzumab botidotin demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of PFS as assessed by the BICR compared with T-DM1[; the beneficial trend for OS of trastuzumab botidotin was also observed.

Currently, the Company has initiated an open, multi-center Phase 2 clinical study of trastuzumab botidotin in the treatment of HER2+ unresectable or metastatic BC that previously received a topoisomerase inhibitor ADC.

About Kelun-Biotech

Kelun-Biotech (6990.HK) is a holding subsidiary of Kelun Pharmaceutical (002422.SZ), which focuses on the R&D, manufacturing, commercialization and global collaboration of innovative biological drugs and small molecule drugs. The company focuses on major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, and in establishing a globalized drug development and industrialization platform to address the unmet medical needs in China and the rest of world. The Company is committed to becoming a leading global enterprise in the field of innovative drugs. At present, the Company has more than 30 ongoing key innovative drug projects, of which 4 projects have been approved for marketing, 1 projects are in the NDA stage and more than 10 projects are in the clinical stage. The company has established one of the world’s leading proprietary ADC and novel DC platforms, OptiDC™, and has 1 ADC project approved for marketing and multiple ADC and novel DC assets in clinical or preclinical research stage. For more information, please visit https://kelun-biotech.com/.

SOURCE Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

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This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.

Companies discussed in this article include RCEL.

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Ingrid de Swart has been nominated to succeed Jos Baeten as CEO and Chair of the Executive Board (EB) of ASR Nederland N.V. (a.s.r.) following the end of his term at the Annual General Meeting (AGM) on 20 May 2026.

Joop Wijn, Chair of the SB of a.s.r., stated : “The Supervisory Board is delighted to nominate Ingrid de Swart as Chair of the Executive Board of a.s.r. Ingrid brings a unifying presence, the experience necessary to ensure continuity in a.s.r.’s strategy, and a forward-looking vision to drive the company’s sustainable growth.

“Although Jos Baeten’s departure will take place at a later date, we would already like to express our profound appreciation for everything he has contributed to a.s.r. over more than 45 years. His dedication and leadership have been invaluable. Under his guidance, a.s.r. successfully navigated the financial crisis, completed a successful IPO, achieved growth both organically and through acquisitions, and became one of the leading insurers in the Netherlands.”

Ingrid de Swart is a seasoned veteran of the financial services industry with over 28 years of experience. She has been a member of a.s.r’s EB since December 1, 2019, serving as COO/CTO, and playing a key role in the company’s strategic direction.

In addition, de Swart has been leading the integration of Aegon Nederland into a.s.r. since October 2022. Prior to joining a.s.r., she served as Chair of the Retail Division on the Statutory Board of Aegon Nederland. Her career also includes leadership roles at Delta Lloyd, and ABN AMRO Verzekeringen.

Jos Baeten, CEO of a.s.r., said: “I have had the privilege of leading a.s.r. for more than 20 years. To this day, I continue to do so with great energy and pleasure, and I will carry on until the AGM. I am very proud of what we have achieved with a.s.r.

“We have a strong team, a strategy focused on growth and a robust balance sheet making a.s.r. a company ready for the future. For me personally, the time has come to hand over the leadership. That is why I have informed the Supervisory Board that I am not available for a new term. I am pleased and proud that Ingrid is my intended successor.”

According to the announcement, Baeten who began his career at the company in 1980, will remain involved until his retirement on 1 December 2026.

The intended appointment of Ingrid de Swart is subject to approval by the regulators and  vote at the upcoming AGM.

The a.s.r. Works Council has issued a positive recommendation, and the SB intends to proceed with the appointment for a period of four years.

a.s.r plans to address the EB vacancy arising from de Swart’s intended appointment at a later date/

 

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