ERAS-801 / Erasca, Katmai Pharma - LARVOL DELTA

Study of ABBV-637 or ABBV-155 With ERAS-801 for People With Glioblastoma (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

New P1 trial • Brain Cancer • CNS Tumor • Glioblastoma • Gliosarcoma • Oncology • Sarcoma • Solid Tumor

A Study to Evaluate ERAS-801 in Patients With Recurrent Glioblastoma (THUNDERBBOLT-1) (clinicaltrials.gov) - P1 | N=52 | Active, not recruiting | Sponsor: Erasca, Inc. | Trial primary completion date: Jan 2025 ➔ Jun 2025

Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

ERAS-801 is a selective brain-penetrant EGFR inhibitor with improved activity against EGFR extracellular domain-mutant glioblastoma (SNO 2024) - "Epidermal growth factor receptor (EGFR) is a driver of nearly 50% of glioblastoma (GBM), yet EGFR inhibitors have failed in GBM (e.g., erlotinib, lapatinib, neratinib, gefitinib, and afatinib) due to poor CNS penetration and/or an inability to inhibit EGFR in its wildtype and extracellular domain (ECD) mutated forms (e.g., EGFRvIII)...Accordingly, relative to other EGFR inhibitors tested in GBM trials (e.g., erlotinib, lapatinib, and osimertinib), ERAS-801 showed superior survival benefit in EGFR altered orthotopic PDX models. Finally, further characterization of ERAS-801 in a preclinical trial of glioma orthotopic PDX models that capture the molecular heterogeneity of GBM, ERAS-801 demonstrated a significant survival benefit at a 25 mg/kg QD dose in the vast majority of EGFR-driven orthotopic GBM PDX models, with FDG-PET imaging serving as a non-invasive biomarker of response. Based on these nonclinical data, ERAS-801 is currently under clinical investigation for GBM."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

ERAS-801 is a selective brain-penetrant EGFR inhibitor with improved activity against EGFR extracellular domain-mutant glioblastoma (SNO 2024) - "Epidermal growth factor receptor (EGFR) is a driver of nearly 50% of glioblastoma (GBM), yet EGFR inhibitors have failed in GBM (e.g., erlotinib, lapatinib, neratinib, gefitinib, and afatinib) due to poor CNS penetration and/or an inability to inhibit EGFR in its wildtype and extracellular domain (ECD) mutated forms (e.g., EGFRvIII)...Accordingly, relative to other EGFR inhibitors tested in GBM trials (e.g., erlotinib, lapatinib, and osimertinib), ERAS-801 showed superior survival benefit in EGFR altered orthotopic PDX models. Finally, further characterization of ERAS-801 in a preclinical trial of glioma orthotopic PDX models that capture the molecular heterogeneity of GBM, ERAS-801 demonstrated a significant survival benefit at a 25 mg/kg QD dose in the vast majority of EGFR-driven orthotopic GBM PDX models, with FDG-PET imaging serving as a non-invasive biomarker of response. Based on these nonclinical data, ERAS-801 is currently under clinical investigation for GBM."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

A Phase 1 study of ERAS-801, a potent, selective, and central nervous system (CNS)-penetrant epidermal growth factor receptor (EGFR) inhibitor, for patients with recurrent glioblastoma multiforme (GBM) (SNO 2024) - "ERAS-801 shows well behaved PK with substantial CNS penetration, preliminary safety, and tolerability in patients with recurrent GBM. The TRAEs were reversible, manageable, and consistent with known toxicities of EGFR inhibitors."

Clinical • P1 data • Brain Cancer • CNS Tumor • Dermatitis • Dermatology • Glioblastoma • Immunology • Oncology • Solid Tumor

ERAS-801: a selective brain-penetrant EGFR inhibitor with improved activity against EGFR extracellular domain-mutant glioblastoma (EORTC-NCI-AACR 2024) - P1 | "Accordingly, relative to other EGFR inhibitors tested in GBM trials (e.g., erlotinib, lapatinib, and osimertinib), ERAS-801 provided superior efficacy in an EGFR-altered intracranial patient-derived orthotopic xenograft (PDOX). Finally, in a preclinical trial of glioma PDOX models that capture the molecular landscape of GBM, ERAS-801 demonstrated a significant overall survival benefit in the majority of EGFR-altered PDOX models at a clinically relevant dose. These preclinical findings have led to the current clinical evaluation of ERAS-801, where Phase I studies (NCT05222802) have confirmed its safety and tolerability at the MTD with plasma exposures exceeding concentrations required for inhibiting tumor growth in GBM PDOX models."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Erasca Announces Strategic In-Licensing of RAS-Targeting Franchise (GlobeNewswire) - "HERKULES-3: ERAS-007 + EC in EC-naïve patients with BRAFm CRC: Deprioritized as clinical efficacy data (data to be presented at ASCO 2024) do not support continued evaluation; THUNDERBBOLT-1: ERAS-801 in recurrent glioblastoma: Due to the desire to focus internal resources on developing naporafenib and the RAS-targeting franchise, Erasca is exploring further advancement of ERAS-801 via select investigator-sponsored trial(s); ERAS-4 pan-KRAS program...Erasca will discontinue its internal pan-KRAS program; provided that certain of the existing ERAS-4 molecules are included in the Medshine agreement as potential backup compounds for ERAS-4001."

Discontinued • Pipeline update • CNS Tumor • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Oncology • Solid Tumor

Erasca Reports Fourth Quarter 2023 and Full Year 2023 Business Updates and Financial Results (GlobeNewswire) - "Key Upcoming Anticipated Milestones:...(i) HERKULES-3: Phase 1b trial for ERAS-007 (ERK inhibitor) plus encorafenib (BRAFTOVI) + cetuximab (ERBITUX) (EC) in EC-naïve patients with BRAFm CRC: Phase 1b combination data expected in the first half of 2024; (ii) THUNDERBBOLT-1: Phase 1 trial for ERAS-801 (CNS-penetrant EGFR inhibitor) in patients with GBM: Initial Phase 1 monotherapy data expected in 2024."

P1 data • Colorectal Cancer • Glioblastoma

A Study to Evaluate ERAS-801 in Patients With Recurrent Glioblastoma (THUNDERBBOLT-1) (clinicaltrials.gov) - P1 | N=52 | Active, not recruiting | Sponsor: Erasca, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Erasca Achieves Key Milestones for Naporafenib and ERAS-801 Programs and Extends Cash Runway (GlobeNewswire) - "ERAS-801 – CNS-penetrant EGFR Inhibitor: Phase 1 monotherapy dose escalation and expansion data in rGBM expected in 2024; ERAS-007 – ERK1/2 Inhibitor: Initial dose expansion data from Phase 1b/2 HERKULES-3 trial further evaluating encouraging early efficacy data with ERAS-007 in combination with EC in EC-naïve patients with BRAF mutant CRC expected between H2 2023 and H1 2024."

P1 data • P1/2 data • Brain Cancer • CNS Tumor • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Oncology • Solid Tumor

Aberrant EGFR activation drives enhanced infiltration of immunosuppressive microglia and macrophages in the glioblastoma tumor immune microenvironment (SITC 2023) - "Lastly, MADR-mEGFRvIII conditioned media polarized bone marrow-derived macrophages to an immunosuppressive M2 (CD206+ CD163+) phenotype in vitro, which was subsequently impaired by pre-treatment of the tumor culture with ERAS-801 or doxycycline. Conclusions Collectively, our work suggests aberrant EGFR signaling supports the development of an immunosuppressive TIME driven by macrophage infiltration and T-cell exhaustion in GBM, and furthermore that EGFR inhibition has an immunostimulatory effect on the microenvironment beyond direct oncogene ablation."

Brain Cancer • CNS Tumor • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD163 • CD8 • EGFR • MRC1 • PD-1 • PTPRC

Erasca Reports Second Quarter 2023 Financial Results and Business Updates (Yahoo Finance) - "THUNDERBBOLT-1: Phase 1 trial for ERAS-801 in patients with recurrent GBM; Initial Phase 1 monotherapy dose escalation data in patients with recurrent GBM expected in the second half of 2023..."

P1 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Erasca Granted FDA Orphan Drug Designation for CNS-Penetrant EGFR Inhibitor ERAS-801 for the Treatment of Malignant Glioma (GlobeNewswire) - "Erasca...announced the United States Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to ERAS-801 for the treatment of malignant glioma, which includes glioblastoma (GBM). ERAS-801 is an orally bioavailable, small molecule EGFR inhibitor that exhibited substantial central nervous system (CNS) penetration in preclinical animal studies.....'We anticipate reporting initial monotherapy data for ERAS-801 from the Phase 1 THUNDERBBOLT-1 trial in patients with recurrent GBM in the second half of 2023.'"

Orphan drug • P1 data • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor

Erasca Granted FDA Fast Track Designation for CNS-Penetrant EGFR Inhibitor ERAS-801 in Patients with Glioblastoma (GlobeNewswire) - "Erasca...announced the United States Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to ERAS-801 for the treatment of adult patients with glioblastoma (GBM) with epidermal growth factor receptor (EGFR) gene alterations. ERAS-801 is an orally bioavailable, small molecule EGFR inhibitor that exhibited substantial central nervous system (CNS) penetration in animal studies."

Fast track designation • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • EGFR

Erasca Reports Fourth Quarter 2022 and Full Year 2022 Financial Results and Business Updates (GlobeNewswire) - "Key Upcoming Anticipated Milestones:...(i) THUNDERBBOLT-1: Phase 1 trial for ERAS-801 in patients with recurrent glioblastoma multiforme (GBM) - Initial Phase 1 data in recurrent GBM in second half of 2023; (ii) AURORAS-1: Phase 1 trial for ERAS-3490 in patients with KRAS G12Cm NSCLC - Initial Phase 1 data in 2024."

P1 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • KRAS

The CNS-penetrant EGFR inhibitor, ERAS-801, shows promising nonclinical activity in a CNS metastases model of EGFR mutant NSCLC (AACR-NCI-EORTC 2022) - P1 | "ERAS-801 at 10 and 25 mpk achieved significantly greater tumor regressions than osimertinib in an intracranial EGFR mutant NSCLC PC9 CDX study. Exhibiting both potent activity against EGFR alterations and high CNS penetration, ERAS-801 shows promising nonclinical activity in cancers outside of GBM, such as CNS metastases of EGFR mutant NSCLC."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Erasca Announces Four Poster Presentations at the Upcoming 34th EORTC-NCI-AACR Symposium (GlobeNewswire) - "High central nervous system (CNS) penetration and comprehensive inhibition of both mutated and wildtype forms are limiting therapeutic factors of approved EGFR inhibitors. ERAS-801 is an oral, highly selective EGFR inhibitor with CNS penetration that is four times higher than approved EGFR inhibitors and comprehensive inhibition against oncogenic EGFRvIII alterations and wildtype. ERAS-801 is highly CNS penetrant and has in vitro activity against EGFR alterations observed in NSCLC. Preclinical data characterizing the activity of ERAS-801 in a CNS metastases model of EGFR mutant NSCLC support superior anti-tumor activity in these lesions with ERAS-801 relative to osimertinib, the current standard of care treatment for patients with EGFR mutant NSCLC."

Preclinical • CNS Tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology

A Phase 1 Study to Evaluate ERAS-801 in Patients With Recurrent Glioblastoma (THUNDERBBOLT-1) (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: Erasca, Inc.

New P1 trial • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Erasca Announces FDA Clearance of IND Application for ERAS-801 in Glioblastoma Multiforme and Collaboration with GCAR for Potential Inclusion in GBM AGILE Clinical Trial (GlobeNewswire) - "Erasca, Inc...announced the United States Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for ERAS-801, an orally available small molecule epidermal growth factor receptor (EGFR) inhibitor specifically designed to have high central nervous system (CNS) penetration for the treatment of recurrent glioblastoma multiforme (rGBM). The company has also entered into a collaboration with the Global Coalition for Adaptive Research (GCAR) to determine the feasibility of the evaluation of ERAS-801 as part of the Glioblastoma Adaptive Global Innovative Learning Environment (GBM AGILE) trial....'We look forward to initiating our THUNDERBBOLT-1 Phase 1 trial evaluating ERAS-801 in patients with recurrent GBM in the first quarter of 2022.'"

IND • Licensing / partnership • New P1 trial • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Erasca Reports Third Quarter 2021 Financial Results and Business Updates (GlobeNewswire) - "Key Upcoming Milestones: (i) ERAS-801: CNS-penetrant EGFR inhibitor - IND filing expected in first quarter of 2022; (ii) HERKULES-4: Phase 1b/2 clinical trial for ERAS-007/MAPKlamp in combination with various agents in patients with hematological malignancies - Dosing of the first patient expected in first quarter of 2022."

IND • New P1/2 trial • Hematological Malignancies • Oncology

Erasca Announces Presentation of Preclinical Data on ERAS-801, a CNS-Penetrant EGFR Inhibitor with Broad Activity against Oncogenic EGFR Alterations, at AACR Conference on Brain Cancer (GlobeNewswire) - "Erasca...announced the presentation of preclinical data for ERAS-801, a small molecule epidermal growth factor receptor (EGFR) inhibitor specifically designed to have high central nervous system (CNS) penetration for the treatment of glioblastoma multiforme (GBM), at the American Association for Cancer Research (AACR) Special Virtual Conference on Brain Cancer....'In more than 30 GBM patient-derived preclinical models, ERAS-801 demonstrated potent activity across mutant and wildtype oncogenic EGFR alterations'."

Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology