CHICAGO & SHANGHAI
JS InnoPharm Ltd initiated the JSI-1187 plus dabrafenib combination dose-escalation phase of the Phase 1 study for patients with locally advanced or metastatic solid tumors with confirmed BRAF V600E/K mutations (NCT04418167). The clinical study is being conducted at 8 NCI-designated Comprehensive Cancer Centers in the U.S.
JSI-1187 is a potent, orally active ERK1 and ERK2 inhibitor. JS InnoPharm holds the U.S. IND for JSI-1187, and this trial is being managed by Strategia Pharmaceuticals LLC, JS InnoPharm’s clinical development partner in the United States.
The JSI-1187 monotherapy dose escalation phase of this study was initiated in 2020 for the treatment of patients with relapsed or refractory, locally advanced or metastatic solid tumors with MAPK pathway mutations, including hyperactivating mutations or gene fusions.
“JSI-1187 is a selective ERK1/2 inhibitor. By utilizing an ERK inhibitor against tumors harboring mutations in the MAPK pathway, we hope to develop more effective single-agent and combination therapies by preventing the early development of resistance seen with current MAPK targeted agents,” said Dr. Linda Paradiso, Chief Development Officer for Strategia Pharmaceuticals.
“Our preclinical studies have demonstrated significant potential of JSI-1187 in combination with dabrafenib, and we are excited to initiate the ERK/BRAF combination treatment at these important clinical cancer sites in the US,” said Dr. Jintao Zhang, Chief Executive Officer for JS InnoPharm.
The Role of ERK in Cancer
MAPK signaling via the RAS-RAF-MEK-ERK pathway plays a critical role in cancer growth and proliferation. Alterations in the MAPK-ERK pathway are found in a variety of cancer types, including KRAS mutations in pancreatic (>90%), biliary tract (3-50%), colorectal (30-50%), lung (25-30%), ovarian (15-39%) and endometrial (18%) cancers; NRAS mutations in melanoma (20%); BRAF V600 mutations in melanoma (50%) and a variety of other tumor types (7% overall).
BRAF/MEK inhibitor combination therapy provides a significant benefit beyond single agent therapy in melanoma and other cancers. However, many patients don’t respond to the combination therapy and most responding patients eventually develop acquired resistance and disease progression. Several mechanisms of acquired resistance have been identified and the reactivation of ERK signaling is central to these mechanisms. Therefore, a combination of ERK inhibition with JSI-1187 and dabrafenib may provide a targeted approach to delay or overcome resistance, as ERK is the most distal kinase of the MAPK signaling pathway.
About JSI-1187
JSI-1187 is a selective and orally administered small molecule inhibitor of ERK1 and ERK2. In preclinical studies, JSI-1187 demonstrated high potency against a variety of tumors with MAPK pathway mutations.
About JS InnoPharm Ltd
JS InnoPharm is a clinical stage biopharmaceutical company, dedicated to the discovery and development of novel chemical entities for cancer therapy, leveraging cutting edge knowledge in mutations, biomarkers, and precision medicine. JS InnoPharm is building an innovative pipeline by internal R&D as well as global partnering and licensing, and developing multiple clinical candidates with differential clinical strategies.
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CONTACT
Vanessa Yan
contact@jsinnopharm.com