Five Novel Lung Cancer Therapies from Hansoh Pharma, Akeso, and Others Designated for Breakthrough Therapy Status in China

▎WuXi AppTec Content Team Report

Avistone: PLB1004 Capsule

Mechanism of Action:EGFR-TKI

Indications: For the treatment of patients who have failed prior EGFR-TKI therapy and haveEGFRMutation,METPatients with locally advanced or metastatic NSCLC with amplification and/or overexpression

Source of screenshot:CDE Official Website

According to the public information from Avistone, Andatini (PLB1004) is one of its research drugs.Novel Small Molecule Tyrosine Kinase Irreversible Inhibitor (EGFR-TKI), which is highly selective and can penetrate the blood-brain barrierNon-clinical efficacy experiments indicate that the compoundEGFR 20Exon insertion mutation,HER2 20Exon insertion mutation,EGFRSensitive mutation,EGFRDrug-resistant mutations andEGFREffective for rare mutations.

At the 2024 World Conference on Lung Cancer (WCLC), researchers announced the results of a Phase 1/2 clinical study that evaluatedPLB1004+c-MET inhibitor vebreltinib, inEGFRMutation-positive,METEfficacy and Safety of EGFR-TKI in NSCLC Patients with Amplified or Overexpressed EGFR.This is also the indication for which the product is proposed to be included in the breakthrough therapy category this time.

44 patients received vebreltinib 100mg + PLB1004 160mg in Phase 1b.vebreltinib  150mg+PLB1004 160mg、vebreltinib 200mg+PLB1004 80mg orVebreltinib 150mg + PLB1004 80mg were included in the safety analysis. Among 44 patients, 36.4% had brain metastases, and 86.4% received third-generation EGFR-TKI treatment.

The study results showed that objective responses occurred at all dose levels of vebreltinib and PLB1004.Partial response (PR) was observed in 19/32 (59.4%) of evaluable patients.. Among the patients in the four dose groups who could be evaluated for efficacy,PR was achieved in 7/12 (58.3%), 6/13 (46.2%), 2/3 (66.7%), and 4/4 (100%) cases, respectively.. In addition,In patients with brain metastases, the ORR was 75.0% (9/12).The ORR of patients previously treated with third-generation EGFR-TKI was 58.6% (17/29).

Researchers believe that vebreltinib+PLB1004 inMETAmplified or OverexpressedEGFRm NSCLC patients who experienced disease progression after prior EGFR-TKI treatment, particularly those with brain metastases receiving third-generation EGFR-TKI therapy, demonstrated promising antitumor activity and manageable safety.

Akeso: AK109 in combination with AK104

Mechanism of Action:VEGFR-2 Monoclonal Antibody Combined with PD-1/CTLA-4 Bispecific Antibody

Indications:Treatment of Advanced Squamous NSCLC Progressed After PD-(L)1 Inhibitor Therapy

Puluo Xi (AK109)Is aFully human VEGFR-2 (anti-vascular endothelial growth factor receptor-2) monoclonal antibody;Cadonilimab (AK104)For aPD-1/CTLA-4 Bispecific Antibody,Already approved in China for the treatment of cervical cancer, gastric cancer and other indications.

According to the public information provided by Akeso,Cadonilimab in combination with Puloci exhibits significant anti-tumor activity and a manageable safety profile, with the potential to overcome immune checkpoint inhibitor resistance through synergistic effects.Cadonilimab in combination with Prolucel for the treatment of advancedGastric adenocarcinoma or gastroesophageal junction adenocarcinomaThe registrational Phase 3 clinical study has been initiated, and the first patient was enrolled in July 2024.

Hansoh Pharma: HS-20093 for Injection

Mechanism of Action:B7-H3 Targeting ADC

Indications: Locally advanced or metastatic non-squamous non-small cell lung cancer that is driver gene-negative and has progressed or recurred after previous platinum-based chemotherapy.NSCLC

HS-20093 is aB7-H3-targeted antibody-drug conjugate (ADC), covalently linked by a fully human anti-B7-H3 monoclonal antibody and a topoisomerase inhibitor (TOPOi) payload., is currently conducting multiple clinical trials in China for the treatment of lung cancer, sarcoma, head and neck cancer, and other solid tumors. Among these, the indication for small cell lung cancer has entered Phase 3 clinical trials. In December 2023, Hansoh Pharma entered into an exclusive licensing agreement with GlaxoSmithKline (GSK), granting the latter a global exclusive license (excluding Greater China) to develop, manufacture, and commercialize the product.

Previously, HS-20093 has been granted Breakthrough Therapy Designation by the U.S. FDA for the treatment ofExtensive-Stage Small Cell Lung Cancer, Osteosarcoma; Included in the NMPA's breakthrough therapy designation in China for the treatment ofExtensive-Stage Small Cell Lung Cancer, Osteosarcoma; Granted Priority Medicine (PRIME) designation by the European Medicines Agency (EMA) for the treatment ofExtensive-Stage Small Cell Lung Cancer。

3SBIOINC: SSGJ-707 Injection

Mechanism of Action:VEGF/PD-1 Bispecific Antibody

Indications: First-line treatment of locally advanced or metastatic NSCLC with positive PD-L1 expression

SSGJ-707 is aVEGF/PD-1 Bispecific AntibodyResearchers are advancing the product in Phase 2 clinical studies, including first-line monotherapy for PD-L1 positive NSCLC, first-line combination chemotherapy for NSCLC, metastatic colorectal cancer (mCRC), and advanced gynecological tumors such as endometrial cancer and ovarian cancer.

According to a previous press release from 3SBIOINC, the interim analysis data of the Phase 2 clinical trial disclosed at the 2025 JPM conference showed that SSGJ-707 demonstrated excellent objective response rate (ORR) and disease control rate (DCR) in the treatment of patients with non-small cell lung cancer and metastatic colorectal cancer.Particularly in the NSCLC indication, whether used as a single agent or in combination with chemotherapy, the product has demonstrated significant anti-tumor activity and favorable safety.Among them,For the first-line treatment of locally advanced or metastatic NSCLC with positive PD-L1 expressionThePhase 2 interim data shows,SSGJ-707 demonstrated good tolerability and safety.ORR was 70.8%, DCR was 100%.

References:

[1] Official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China.Retrieved Apr 9，2025, From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c