China-based Dizal Pharmaceutical Co., Ltd (SHA: 688192) has announced receiving approval from the National Medical Products Administration (NMPA) to conduct a Phase II clinical study assessing the safety, tolerability, and efficacy of its next-generation epidermal growth factor receptor (EGFR) inhibitor sunvozertinib (DZD9008) in combination with the JAK1 inhibitor golidocitinib (DZD4205). The study will focus on patients with non-small-cell lung cancer (NSCLC) who have failed standard treatments and have the EGFR mutation.
Clinical Development and Efficacy
Sunvozertinib is being developed to treat EGFR exon 20 insertion mutation NSCLC and is undergoing international clinical studies in China, the US, and other regions. Data from the regulatory clinical trials (WU-KONG6) in China have shown a tumor response rate (ORR) of up to 59.8% for sunvozertinib. Preclinical and preliminary clinical trials have also demonstrated the drug’s efficacy against EGFR-sensitive mutations, T790M mutations, and HER2 exon 20 insertion mutations.
DZD4205 is an oral, highly selective JAK1 inhibitor being developed to treat blood tumors, solid tumors, and autoimmune diseases. The drug is undergoing pivotal clinical trials in China, the US, South Korea, and Australia and is recognized as the world’s first and only highly selective JAK1 inhibitor at the global regulatory clinical stage for T cell lymphoma treatment. DZD4205 obtained fast-track status for use in relapsed or refractory peripheral T cell lymphoma (r/r PTCL) in the US in 2022.
Mechanism and Synergistic Effect
Previous studies have shown that EGFR TKI treatment of lung cancer models with EGFR mutations can further activate the JAK1/STAT3 pathway, leading to tumor cell survival and residual lesions. Therefore, blocking both the EGFR and JAK/STAT pathways simultaneously is expected to overcome resistance to EGFR TKI treatment. In NSCLC transplanted tumor models with EGFR-sensitive and/or drug-resistant mutations, the combination of sunvozertinib and golidocitinib demonstrated a synergistic anti-tumor effect, offering a promising treatment option for this patient population.
Future Outlook
The approval for the Phase II clinical study of the sunvozertinib and golidocitinib combination highlights Dizal Pharmaceutical’s commitment to advancing innovative treatments for NSCLC. With demonstrated efficacy and safety profiles, the combination therapy has the potential to address significant unmet needs in patients who have failed standard treatments. Dizal’s ongoing efforts in clinical development underscore its dedication to improving patient outcomes in oncology.-Fineline Info & Tech
