ERK2

HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM; HKEX:​13) today highlights that new clinical data from several ongoing studies with HUTCHMED investigational drug candidates fruquintinib, surufatinib and HMPL-295, which will be presented at the upcoming European Society for Medical Oncology (“ESMO”) Asia Congress, taking place on December 1-3, 2023 in Singapore, and the ESMO Immuno-Oncology Congress, taking place on December 6-8, 2023 in Geneva, Switzerland. This presentation will report data from a multi-center, open-label clinical trial to evaluate safety, tolerability, pharmacokinetics and preliminary efficacy profile of HMPL-295, and to determine the maximum tolerated dose (“MTD”) and recommended Phase II dose in patients with advanced malignant solid tumors. The continuous-administration MTD was determined to be 50 mg QD, and intermittent administration studies are ongoing. HMPL-295 is an investigational, selective, oral inhibitor of extracellular signal-regulated kinase 1 & 2 (ERK1/2), which is a downstream component of the RAS-MAPK pathway signaling cascade. The investigational compound has the potential to address intrinsic or acquired resistance from upstream mechanisms such as RAS, RAF and MEK. HMPL-295 is one of several investigational compounds discovered by HUTCHMED that target the RAS-MAPK pathway. These presentations will report results from the cervical cancer and NSCLC patient cohorts of the basket clinical trial in China of fruquintinib plus sintilimab. This trial is an open-label, multi-center, non-randomized, Phase ІІ study to assess the safety and efficacy of fruquintinib in combination with sintilimab in patients with advanced cervical cancer, endometrial cancer (“EMC”), gastric cancer (GC), hepatocellular carcinoma (HCC), NSCLC or renal cell carcinoma (“RCC”). Data from the EMC and RCC cohorts of this trial led to the initiation of registration enabling programs. This combination treatment showed promising antitumor activity in advanced cervical cancer and NSCLC patients, particularly for patients with PD-L1 positive status. This combination treatment also showed manageable toxicity profiles consistent with that seen in other cohorts. Fruquintinib is a selective oral inhibitor of vascular endothelial growth factor receptors (“VEGFR”) -1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for high drug exposure, sustained target inhibition, and flexibility for the potential use as part of combination therapy. Fruquintinib has demonstrated a manageable safety profile and is being investigated in combination with other anti-cancer therapies including the approved PD-1 inhibitor, sintilimab. Investigator-initiated studies presentations: HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch-med.com or follow us on LinkedIn. The content above comes from the network. if any infringement, please contact us to modify.

CHICAGO & SHANGHAI--(BUSINESS WIRE)-- 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.

Promising preliminary monotherapy data for ERK1/2 inhibitor ERAS-007 and SHP2 inhibitor ERAS-601 in advanced solid tumors, which had favorable safety, tolerability, and efficacy profiles that support combination development BRAF Class 2 and 3 alterations have no approved targeted therapies and represent up to 25% of all BRAF-driven tumors SAN DIEGO, CA, USA I December 20, 2022 I Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, today announced dosing of the first patient in the HERKULES-1 Phase 1b trial evaluating ERK1/2 inhibitor ERAS-007 in combination with SHP2 inhibitor ERAS-601 (together, Erasca’s first MAPKlamp) in patients with RAS/MAPK pathway-altered solid tumors. “We are pleased with our team’s efficient execution that resulted in dosing the first patient in our MAPKlamp trial in 2022 ahead of schedule,” said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. “ERK and SHP2 inhibition with ERAS-007 and ERAS-601 targets critical downstream and upstream nodes in the RAS/MAPK pathway, offering a rational approach that is supported by early clinical data that we presented at our R&D Day in September. Notably, we reported four responses in nine patients with BRAF-driven tumors to either monotherapy ERAS-007 or ERAS-601. Three of these responses were in tumors with BRAF Class 2 or 3 alterations, including a confirmed response to monotherapy SHP2 inhibition in a patient with a BRAF Class 3 alteration, which is dependent on upstream receptor tyrosine kinase (RTK) activation. We look forward to exploring the potential to address the high unmet need in these BRAF subtypes, which have no approved targeted therapies and represent up to 25% of all BRAF-driven tumors.” The MAPKlamp portion of HERKULES-1 will initially examine the safety, tolerability, and preliminary efficacy of ERAS-007 in combination with ERAS-601 in patients with RAS/MAPK pathway-altered solid tumors. After a recommended dose is determined, the Phase 2 expansion portion will further evaluate the safety and efficacy of the combination in patients with different mutational subtypes, including BRAF Class 2 and 3 patients. ERAS-007 and ERAS-601 had favorable monotherapy safety and tolerability profiles with largely non-overlapping treatment-related adverse events that support combination development. Forty-four percent (4/9) of patients with BRAF-driven tumors responded (one confirmed and three unconfirmed PRs) to single agent ERAS-007 or ERAS-601, including three (one confirmed and two unconfirmed PRs) in tumors with BRAF Class 2 and 3 alterations. The clinical data referred to above was presented at Erasca’s September 7, 2022 R&D Day, and consisted of a retrospective pooled interim analysis of monotherapy ERAS-007 and ERAS-601 data, with data cutoff dates of 11/6/20, 7/11/22, and 5/16/22 for the ASN007-101, FLAGSHP-1, and HERKULES-1 trials, respectively. About ERAS-007 ERAS-007 is a potential best-in-class ERK1/2 inhibitor being investigated alone or in combination with different inhibitors targeting upstream nodes of the RAS/MAPK pathway as part of Erasca’s MAPKlamp strategy. The extracellular signal-regulated kinases (ERK), ERK1 and ERK2, belong to a family of serine-threonine kinases that regulate cellular signaling and comprise the terminal node of the RAS/MAPK pathway. ERAS-007 is being investigated across the series of HERKULES clinical trials that span multiple tumor types and includes both monotherapy and combinations with approved and investigational agents, such as RTK, SHP2, RAS, RAF, and/or cell cycle inhibitors. HERKULES-1 is a Phase 1b/2 clinical trial for ERAS-007 as a single agent and in combination with the SHP2 inhibitor ERAS-601 (together, Erasca’s first MAPKlamp) in advanced solid tumors. HERKULES-2 is a Phase 1b/2 master protocol clinical trial for ERAS-007 in combination with various agents in patients with non-small cell lung cancer (NSCLC). HERKULES-3 is a Phase 1b/2 master protocol clinical trial for ERAS-007 in combination with various agents in patients with gastrointestinal (GI) cancers. About ERAS-601 ERAS-601 is a potential best-in-class oral, selective SHP2 inhibitor being investigated alone or in combination. SHP2 acts as a convergent node for receptor tyrosine kinase (RTK) signaling, relaying growth and survival signals from RTKs to intracellular signaling pathways. ERAS-601 combined with the ERK1/2 inhibitor ERAS-007 makes up Erasca’s first innovative MAPKlamp strategy. ERAS-601 is being investigated across a series of clinical trials that span multiple tumor types and include both monotherapy and combinations with approved and investigational agents. FLAGSHP-1 is a Phase 1/1b clinical trial evaluating ERAS-601 as a monotherapy in advanced solid tumors and in combination in triple wildtype (KRAS/NRAS/BRAF wildtype) CRC and human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). HERKULES-1 is a Phase 1b/2 clinical trial that includes evaluation of ERAS-601 in combination with ERAS-007 in advanced solid tumors. HERKULES-2 is a Phase 1b/2 master protocol clinical trial that includes evaluation of ERAS-601 in combination with various agents in patients with non-small cell lung cancer (NSCLC). About Erasca At Erasca, our name is our mission: To eras e ca ncer. We are a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers. Our company was co-founded by leading pioneers in precision oncology and RAS targeting to create novel therapies and combination regimens designed to comprehensively shut down the RAS/MAPK pathway for the treatment of cancer. We have assembled what we believe to be the deepest RAS/MAPK pathway-focused pipeline in the industry. We believe our team’s capabilities and experience, further guided by our scientific advisory board which includes the world’s leading experts in the RAS/MAPK pathway, uniquely position us to achieve our bold mission of erasing cancer. SOURCE: Erasca