APL-101

Overview

APL-101 (also known as CBT-101, PLB1001, bozitinib, vebreltinib) is an orally bioavailable, highly selective small‑molecule inhibitor of the MET receptor tyrosine kinase. It has clinical data in MET‑altered cancers, most notably MET exon 14 skipping (METex14) non–small cell lung cancer (NSCLC). In China, vebreltinib received conditional approval in November 2023 for METex14 NSCLC and, in April 2024, approval for certain gliomas with PTPRZ1–MET fusion; development continues elsewhere in ongoing phase 1/2 studies. (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

Vebreltinib inhibits MET kinase activity (ATP‑competitive), blocking downstream signaling of the HGF/MET axis. Preclinical work shows high potency and selectivity for MET (Ki ≈ 2.2 nM; cellular IC50 ≈ 0.52 nM) and brain penetration, with antitumor activity across MET‑dysregulated patient‑derived models. (aacrjournals.org)

Efficacy

• MET exon 14 skipping NSCLC (KUNPENG, phase 2, single‑arm; n=52 evaluable): In the primary cohort treated with vebreltinib 200 mg twice daily, blinded independent review reported ORR 75.0% (95% CI 61.1–86.0), disease control rate 96.2%, median duration of response 16.5 months, median PFS 14.3 months, and median OS 20.3 months (3‑year OS rate 35.1%). Subgroups included ORR 77.1% in treatment‑naïve (n=35) and 70.6% in previously treated (n=17); ORR 100% in those with baseline brain metastases (n=5). (pmc.ncbi.nlm.nih.gov)

• Basket cohort with non‑CNS MET fusions (SPARTA, phase 2, preliminary; n=14): Confirmed ORR 43% (1 complete response in 3rd‑line NSCLC; partial responses in NSCLC, pancreatic, and intrahepatic bile duct cancers). Median PFS 4.5 months; median OS 12.4 months; median time to response 3.7 months; median duration of response 5.6 months. (ir.apollomicsinc.com)

• Glioma program: The approval in China for IDH‑mutant astrocytoma (WHO grade 4)/glioblastoma with PTPRZ1–MET fusion followed a randomized phase 2/3 effort; earlier work (phase 1) in recurrent high‑grade glioma with MET alterations demonstrated brain penetration and signals of activity. (ir.apollomicsinc.com)

Ongoing/global development: The SPARTA study (NCT03175224) is an international phase 1/2, multi‑cohort trial evaluating vebreltinib in METex14 NSCLC and MET‑dysregulated solid tumors, including cohorts exploring combinations (e.g., with EGFR TKIs for MET‑mediated resistance). A China partner study, KUNPENG (NCT04258033), provided the METex14 NSCLC data summarized above. (mycancergenome.org)

Safety

In the KUNPENG study, treatment‑related adverse events (TRAEs) were predominantly grade 1–2. The most common TRAEs (≥20% across 135 enrolled patients) were peripheral edema (56.3%), hypoalbuminemia (27.4%), hypoproteinemia (25.9%), and anemia (20.7%). No new safety signals emerged with longer follow‑up. The recommended dose used in phase 2 was 200 mg twice daily. (ascopubs.org)

Further reading

• Journal article (KUNPENG phase 2, METex14 NSCLC): Vebreltinib for Advanced NSCLC Harboring MET exon 14 Skipping Mutation. Journal of Clinical Oncology, 2024. (pmc.ncbi.nlm.nih.gov)
• ASCO 2024 abstract (updated KUNPENG follow‑up): JCO 42(16_suppl):8557. (ascopubs.org)
• Preclinical pharmacology: AACR Cancer Research abstract (brain‑penetrant MET inhibitor; potency/selectivity). (aacrjournals.org)
• Secondary glioblastoma genomics and early PLB1001 clinical experience: Cell 2018 (with Research Watch summary in Cancer Discovery). (pubmed.ncbi.nlm.nih.gov)
• SPARTA trial registry (global, phase 1/2): NCT03175224. (mycancergenome.org)
• Regulatory context (China approvals): Avistone/Apollomics announcements (METex14 NSCLC; PTPRZ1–MET fusion glioma). (businesswire.com)

Notes: Outside China, vebreltinib remains investigational as of October 7, 2025; efficacy and safety are being further defined in ongoing trials. (mycancergenome.org)

Last updated: Oct 2025