China-based Shanghai Henlius Biotech (HKG: 2696) has announced that the National Medical Products Administration (NMPA) has approved a Phase Ib/II clinical study for its BRAF V600E inhibitor HLX208. The study will evaluate the combination of HLX208 with HaiSiZhuang (serplulimab) plus standard therapies (cetuximab or trametinib) for the treatment of advanced solid tumors with BRAF V600E mutation.
HLX208 Profile and Mechanism
HLX208 (also known as RX208) is a small molecule BRAF V600E inhibitor licensed from NeuPharma, a fellow Chinese firm. The drug demonstrated outstanding efficacy and safety in preclinical studies. BRAF is a key upstream regulator in the MAPK/ERK signaling pathway, and the V600E mutation causes continuous activation of the BRAF protein. HLX208 is being developed to treat various tumors, including colorectal cancer, thyroid tumors, melanoma, lung cancer, brain cancer, as well as adult Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD). In January 2022, HLX208 received approval in China for a Phase Ib/II clinical study in BRAF V600E or BRAF V600 mutation-positive advanced solid tumors, either as monotherapy or in combination with other drugs. The first patient has been dosed in a Phase II clinical study for HLX208 in LCH and ECD with BRAF V600E mutation. Preclinical studies have shown that the combination of BRAF inhibitors and trastuzumab exerts synergistic effects.
Serplulimab Profile and Clinical Development
Serplulimab has been approved for the treatment of unresectable or metastatic microsatellite highly unstable (MSI-H) solid tumors that have failed standard therapy, as well as in combination with chemotherapy for first-line squamous non-small cell lung cancer (sqNSCLC). Supplementary New Drug Applications (sNDAs) for serplulimab in combination with chemotherapy for first-line extensive-stage small cell lung cancer (SCLC) and first-line esophageal squamous cell carcinoma (ESCC) were accepted for review in China in April and August 2022, respectively. Currently, serplulimab is involved in multiple ongoing clinical studies globally, including as a component of 10 combination therapies.-Fineline Info & Tech
