▎WuXi AppTec Content Team Report

August 20，Hansoh Pharma announces that its partner, GSK, has received Breakthrough Therapy Designation from the U.S. FDA for HS-20093 (GSK5764227). This is a B7-H3 targeted antibody-drug conjugate (ADC) currently being evaluated for...Treatment of Patients with Extensive-Stage Small Cell Lung Cancer (ES-SCLC) Who Progressed During or After Platinum-Based Chemotherapy (Recurrent or Refractory)。  

HS-20093 is a novel B7-H3-targeted ADC, covalently linked by a fully humanized B7-H3 monoclonal antibody and a topoisomerase inhibitor (TOPOi) payload.Multiple phase 1 and phase 2 clinical studies for the treatment of lung cancer, sarcoma, head and neck cancer, and other solid tumors are currently being conducted in China.On December 20, 2023, Hansoh Pharma entered into an exclusive licensing agreement with GSK worth over $1.7 billion, granting GSK a global exclusive license (excluding mainland China, Hong Kong, Macao, and Taiwan) to develop, manufacture, and commercialize HS-20093.

According to the introduction in Hansoh Pharma's press release, the recent FDA Breakthrough Therapy Designation was supported by the ongoing efforts of Hansoh Pharma.1PeriodARTEMIS-001 Open-label, Multi-centerFirst-in-Human Clinical TrialData support. The trial involved more than 200 patients and evaluated HS-20093 forSafety, Tolerability, and Preliminary Antitumor Activity in Locally Advanced or Metastatic Solid Tumors (Including Relapsed or Refractory ES-SCLC)The trial results will be announced at the World Conference on Lung Cancer (WCLC) to be held in the United States from September 7 to 10, 2024.

At the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Hansoh Pharma announced the preliminary results of the ARTEMIS-001 study. The ARTEMIS-001 study is divided into two parts: The first part is a Phase 1a dose-escalation study, which evaluates the safety, tolerability, pharmacokinetic profile, and preliminary efficacy of HS-20093 in subjects with advanced solid tumors who have failed or are intolerant to existing standard treatments. This is done through an accelerated titration combined with the "i3+3" design, sequentially escalating through pre-set dose cohorts. The second part is a Phase 1b dose-expansion study, assessing the efficacy and safety of HS-20093 at potential target doses in patients with solid tumors such as lung cancer, prostate cancer, esophageal cancer, and head and neck cancers.The dosing regimen is intravenous injection, once every 3 weeks (Q3W).

As of March 10, 2023, a total of 53 subjects (without pre-screened targets, with retrospective testing for B7-H3 protein expression) have been enrolled in the dose escalation phase, including those with non-small cell lung cancer, small cell lung cancer, bone and soft tissue sarcoma, esophageal cancer, melanoma, and breast cancer.Results of safety and tolerability showed,Three subjects experienced dose-limiting toxicity, and the maximum tolerated dose (MTD) was 12.0 mg/kg Q3W.

Efficacy data showed that a total of 50 subjects had at least one tumor assessment after baseline. According to the investigator's evaluation based on RECIST 1.1 criteria, the objective response rate (ORR) was 30.0%.The disease control rate was 86.0%.The median progression-free survival (mPFS) was 5.4 months. In subjects with small cell lung cancer, the ORR was 63.6%, with all tumor responses occurring at the first efficacy assessment, and the mPFS was 4.7 months, with a 3-month PFS rate of 72.7%. HS-20093 still demonstrated antitumor efficacy in subjects with small cell lung cancer who had previously failed irinotecan treatment.

Researchers believe that the Phase 1a clinical data show that HS-20093 has manageable safety, with the MTD at 12.0 mg/kg, and demonstrates excellent anti-tumor efficacy in subjects with various advanced solid tumors who have failed or are intolerant to existing standard treatments, particularly showing superior efficacy in small cell lung cancer. The clinical data support the further development of HS-20093, which is currently being explored for its efficacy and safety at doses ranging from 8.0 to 12.0 mg/kg across multiple types of advanced solid tumors.

[1] Hansoh Pharma HS-20093 (B7-H3 ADC) Receives FDA Breakthrough Therapy Designation. Retrieved Aug 20, 2024, from https://mp.weixin.qq.com/s/WPSGJUZ7JKo4lxEdHZkt9g

[2] 2023 ASCO | Hansoh Pharma's B7-H3 ADC, c-MET TKI Research Findings Unveiled, Clinical Potential Gains International Recognition. Retrieved June 5, 2023, from https://mp.weixin.qq.com/s/6cuSx1FIq-buo5hWim4O8w