SW-682 / EMD Serono - LARVOL DELTA

Molecular profiling of SW-682, a pan-TEAD inhibitor, as monotherapy and in combination with other treatments across tumor types (AACR 2025) - "However, Hippo pathway gene alterations alone were not sufficient to predict sensitivity to combination of SW-682 and sotorasib. Therefore, we sought to characterize molecular signatures that correlated with combination benefits by analyzing baseline DNA mutation status and RNA expression levels in each model.In conclusion, these results help elucidate SW-682 molecular signatures across different tumor types and can support combination strategies for SW-682 in clinical investigation."

Combination therapy • Monotherapy • Head and Neck Cancer • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • KRAS • TAFAZZIN

Targeting YAP/TAZ-TEAD signaling as a therapeutic approach in head and neck squamous cell carcinoma. (PubMed, Cancer Lett) - "Here, we provide the pre-clinical evidence for the antitumor activity of novel smTEADi, SW-682 in HPV-negative HNSCC. A HNSCC-specific TEADi target gene set was defined from RNA-seq data, which is highly expressed in HNSCC tissues and predicts poor prognosis of HPV-negative HNSCC patients. Our results underscore that YAP/TAZ-TEAD-mediated growth-promoting programs represent a vulnerability in HPV-negative HNSCC, thus providing a pre-clinical rationale for the future evaluation of YAP/TAZ-TEAD targeting strategies as a therapeutic approach for HPV-negative HNSCC patients."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • FAT1 • WWTR1 • YAP1

SpringWorks Therapeutics Reports Preliminary Fourth Quarter and Full Year 2024 Financial Results and Provides Business Updates at 43rd Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "Emerging Pipeline: SpringWorks expects additional data to be presented by MapKure from the brimarafenib monotherapy trial in the second half of 2025. Continue enrolling patients in Phase 1 trial of SW-682 in Hippo-mutant solid tumors. File an Investigational New Drug (IND) application for SW-3431 by the end of 2025."

Enrollment status • IND • P1 data • Oncology • Solid Tumor

Rational combination of pan-TEAD inhibitor SW-682 and MEK inhibitor mirdametinib in head and neck squamous cell carcinomas leads to synergistic response (EORTC-NCI-AACR 2024) - "The pan-TEAD inhibitor SW-682 modulates tumor growth in HNSCC models harboring aberrant Hippo pathway signaling both in vitro and in vivo. The combination of SW-682 with mirdametinib resulted in enhanced anti-tumor responses in HNSCC models. These observations may provide a rational combination approach for clinical studies."

Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CCN1 • CTGF • FAT1 • WWTR1 • YAP1

TEAD inhibition by SW-682 potentiates activity of targeted therapies in NSCLC models (EORTC-NCI-AACR 2024) - "Combinations of SW-682 with EGFR (osimertinib), KRAS G12C (sotorasib or adagrasib), or MAPK inhibitors (brimafenib+mirdametinib dual combo) were tested in respective mutant-specific cell lines in vitro. TEAD inhibitor SW-682 exhibited synergistic activity with EGFR and RAS/MAPK pathway inhibitors in inhibiting proliferation of NSCLC cell models in vitro and sensitized the response of KRAS G12C NSCLC models to sotorasib treatment in vivo. The preclinical findings suggest that combination with SW-682 could enhance efficacy and response durability of targeted therapies in NSCLC models, thus supporting investigation of SW-682 combinations in clinical studies."

Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • TAFAZZIN

SpringWorks Therapeutics Reports Second Quarter 2024 Financial Results and Recent Business Highlights (GlobeNewswire) - "The Company expects to complete the submission of an MAA for mirdametinib for the treatment of children and adults with NF1-PN in the European Union in the second half of 2024....SpringWorks expects to publish the ReNeu trial results in a peer-reviewed journal in the second half of 2024....A Phase 1b trial evaluating brimarafenib (BGB-3245) in adult patients with RAF mutant solid tumors is ongoing; additional data from the dose expansion portion of the study is expected to be presented in the first half of 2025. SpringWorks initiated a Phase 1a trial of SW-682, an investigational novel, oral, potent, and selective pan-TEAD inhibitor, in Hippo-mutant solid tumors in the second quarter of 2024."

EMA filing • P1 data • P2b data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Neurofibromatosis • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

TEAD-AST-101: SW-682 in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=186 | Recruiting | Sponsor: SpringWorks Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Mesothelioma • Oncology • Solid Tumor

SpringWorks Therapeutics Reports First Quarter 2024 Financial Results and Highlights Recent Business Updates (GlobeNewswire) - "Emerging Pipeline: (i) On track to present additional data from the dose expansion portion of the Phase 1b trial evaluating brimarafenib (BGB-3245) in adult patients with RAF mutant solid tumors in the second half of 2024...; (ii) On track to initiate a Phase 1a trial of SW-682, an investigational novel, oral, potent, and selective pan-TEAD inhibitor, in Hippo-mutant solid tumors in the second quarter of 2024."

New P1 trial • P1 data • Solid Tumor

SpringWorks Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Highlights Recent Business Updates (GlobeNewswire) - "The FDA cleared the Investigational New Drug (IND) application submitted by MapKure for a combination study of brimarafenib with panitumumab, a monoclonal antibody targeting EGFR, in colorectal and pancreatic cancer patients with known MAPK pathway mutations. MapKure expects to initiate a Phase 1b trial in the first quarter of 2024....The FDA cleared the IND application for SW-682, a novel, oral, potent, and selective TEA Domain inhibitor designed to treat tumors driven by Hippo pathway mutations. SpringWorks plans to initiate a Phase 1a trial of SW-682 in Hippo mutant solid tumors in the first half of 2024."

IND • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

SW-682 in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=186 | Not yet recruiting | Sponsor: SpringWorks Therapeutics, Inc.

New P1 trial • Mesothelioma • Oncology • Solid Tumor

SpringWorks Therapeutics Reports Third Quarter 2023 Financial Results and Recent Business Highlights (GlobeNewswire) - "SpringWorks expects to present topline data from the pediatric and adult cohorts of the Phase 2b ReNeu trial evaluating mirdametinib, an investigational MEK inhibitor, in NF1-associated plexiform neurofibromas (NF1-PN) in the fourth quarter of 2023. If these data are positive, SpringWorks plans to submit an NDA to the FDA for mirdametinib for the treatment of NF1-PN in the first half of 2024; SpringWorks plans to file an IND for SW-682, the Company's TEAD inhibitor development candidate, in the fourth quarter of 2023."

IND • P2b data • Oncology • Solid Tumor

A novel irreversible TEAD inhibitor, SWTX-143, blocks Hippo pathway transcriptional output and causes tumor regression in preclinical mesothelioma models. (PubMed, Mol Cancer Ther) - "Finally, SWTX-143 also selectively impaired the growth of NF2-mutant kidney cancer cell lines, suggesting that the sensitivity of mesothelioma models to these YAP/TAZ-TEAD inhibitors can be extended to other tumor types with aberrations in Hippo signaling. In brief, we describe a novel and specific YAP/TAZ-TEAD inhibitor that has potential to treat multiple Hippo-mutant solid tumor types."

Journal • Preclinical • Genito-urinary Cancer • Kidney Cancer • Lung Cancer • Mesothelioma • Oncology • Renal Cell Carcinoma • Solid Tumor • LATS2 • NF2 • TAFAZZIN • TEAD1

SW-682: A novel TEAD inhibitor for the treatment of cancers bearing mutations in the Hippo signaling pathway (AACR 2023) - "Moreover, to identify new indications that may benefit from TEAD inhibition, we screened patient-derived 3D organoid tumor cells and matching patient-derived xenograft models that have been molecularly profiled. In summary, SW-682 is a potent and selective investigational TEAD inhibitor which demonstrated anti-tumor effects in models harboring aberrant expression of the Hippo pathway, suggesting therapeutic potential in multiple Hippo-mutant solid tumors."

Lung Cancer • Melanoma • Mesothelioma • Oncology • Solid Tumor • BRAF • CCN1 • CTGF • NRAS

SpringWorks Therapeutics Highlights 2022 Accomplishments and Anticipated Milestones for 2023 at the 41st Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "Anticipated 2023 Key Milestones: Present additional data from BeiGene-sponsored Phase 1b/2 trial evaluating mirdametinib in combination with lifirafenib in adult patients with RAS/RAF mutant and other MAPK pathway aberrant solid tumors at a medical conference in the first half of 2023; Dose first patient in BGB-3245 + mirdametinib combination study in MAPK-mutant solid tumors in the first half of 2023; File Investigational New Drug Application for TEAD inhibitor SW-682."

IND • P1/2 data • Trial status • Oncology • Solid Tumor