- |||||||||| ulixertinib (BVD-523) / BioMed Valley Discoveries, Truqap (capivasertib) / Otsuka, AstraZeneca
Journal: Proteomic profiling reveals CEACAM6 function in driving gallbladder cancer aggressiveness through integrin receptor, PRKCD and AKT/ERK signaling. (Pubmed Central) - Oct 29, 2024 ERK and AKT signaling and their downstream target genes were regulated by CEACAM6 and thus the treatment with AKT inhibitor capivasertib or ERK inhibitor ulixertinib mitigated the CEACAM6-induced migration. These findings demonstrate that CEACAM6 is crucially involved in gallbladder cancer progression by promoting migration and inhibiting cell adhesion through ERK and AKT signaling providing specific options for treatment of CEACAM6-positive cancers.
- |||||||||| Ibrance (palbociclib) / Pfizer, ulixertinib (BVD-523) / BioMed Valley Discoveries
Trial completion date, Trial primary completion date, Combination therapy, Metastases: Ulixertinib/Palbociclib in Patients With Advanced Pancreatic and Other Solid Tumors (clinicaltrials.gov) - Aug 1, 2024 P1, N=45, Recruiting, Trial primary completion date: Mar 2026 --> Mar 2028 Trial completion date: Apr 2026 --> Nov 2026 | Trial primary completion date: Jul 2024 --> Aug 2025
- |||||||||| RMC-6236 / Revolution Medicines
RRAS and RRAS2 Mutations Are Oncogenic Drivers in Lung Cancer and are Sensitive to the Pan-RAS Inhibitor RMC-6236 (Exhibit Hall) - Jul 24, 2024 - Abstract #IASLCWCLC2024IASLC_WCLC_1488; P1 Oncogenic R RAS/RRAS2 mutations were detected in LUAD at a rate similar to some other well-characterized lung cancer drivers, such as HRAS/NRAS hotspot mutations or NRG1 fusions. Our study supports the inclusion of RRAS /RRAS2 into routine molecular diagnostic protocols for precision oncology and clinical development of pan-RAS inhibitors, such as RMC-6236, for patients with these driver mutations in order to fully realize the potential benefit of RAS-targeted therapies.
- |||||||||| ulixertinib (BVD-523) / BioMed Valley Discoveries
Enrollment change, Trial completion date, Trial termination, Trial primary completion date, Combination therapy, Pan tumor, Metastases: Trial of Ulixertinib in Combination With Hydroxychloroquine in Patients With Advanced Gastrointestinal (GI) Malignancies (clinicaltrials.gov) - Jul 22, 2024 P2, N=47, Terminated, Our study supports the inclusion of RRAS /RRAS2 into routine molecular diagnostic protocols for precision oncology and clinical development of pan-RAS inhibitors, such as RMC-6236, for patients with these driver mutations in order to fully realize the potential benefit of RAS-targeted therapies. N=215 --> 47 | Trial completion date: Mar 2025 --> Jul 2024 | Recruiting --> Terminated | Trial primary completion date: Dec 2024 --> May 2024; Lack of Enrollment for Remaining Open Baskets
- |||||||||| FGFR3 altered bladder cancer exhibits a lineage-dependent vulnerability (Section 23) - Mar 5, 2024 - Abstract #AACR2024AACR_6731;
Moreover, the synergy in FGFR3-mutant cells was superior to that of SHP2 inhibitor SHP099 or the ERK inhibitor BVD-523...By contrast, Sel120+Erdafitinib induced complete responses in 8/10 mice compared to 6/10 mice for SHP099+Erdafitinib...Our results suggest an immediate and promising benefit in combining either CDK8/19 or SHP2 inhibitors with Erdafitinib in treating patients with FGFR3 alteration driven bladder cancers. Furthermore, we identified a strategy in targeting lineage modulators as sensitizers to existing therapies.
- |||||||||| ulixertinib (BVD-523) / BioMed Valley Discoveries
Impaired PPAR? Activation Exacerbates Infection-Induced Lung Injury (Walter E. Washington Convention Center, Room 151 A (Street Level)) - Mar 25, 2023 - Abstract #ATS2023ATS_2664; in monocyte-derived macrophages exacerbates lung injury and the severity of LRTIs. Targeting ERK activationmay provide a novel therapeutic target to protect against cadmium and infection-induced lung injury.
- |||||||||| ulixertinib (BVD-523) / BioMed Valley Discoveries
Journal: The first-in-class ERK inhibitor ulixertinib shows promising activity in MAPK-driven pediatric low-grade glioma models. (Pubmed Central) - Mar 16, 2023 Targeting ERK activationmay provide a novel therapeutic target to protect against cadmium and infection-induced lung injury. These data indicate a high clinical potential of ulixertinib for the treatment of pLGG and strongly support its first clinical evaluation in pLGG as single agent and in combination therapy in a currently planned international phase I/II umbrella trial.
- |||||||||| zunsemetinib (ATI-450) / Aclaris, ulixertinib (BVD-523) / BioMed Valley Discoveries
TNF-MK2 signaling drives protective autophagy following MAPK pathway inhibition in pancreatic cancer (Section 15; Poster Board #20) - Mar 14, 2023 - Abstract #AACR2023AACR_6095; The combination of MK2 inhibitor ATI-450 and ERK inhibitor ulixertinib was more effective in curbing the growth of PDAC patient-derived xenograft in vivo and prolonged the survival of autochthonous PDAC mice (KPC model). Overall, our study provided novel insights on the mechanisms that drive protective autophagy following MAPK pathway inhibition and a rationale and feasible therapeutic combination that can be tested in clinical trials for PDAC patients.
- |||||||||| ulixertinib (BVD-523) / BioMed Valley Discoveries
The combination of ulixertinib (ERK1/2 Inhibitor) and KRASG12C inhibition demonstrates significant efficacy in preclinical models (Section 14; Poster Board #28) - Mar 14, 2023 - Abstract #AACR2023AACR_4914; Expression of the mutant KRAS alleles were readily confirmed from RNA sequencing data in all models. Gene expression analysis showed differential expression of MAPK pathway genes in monotherapy versus combination therapy treated groups.In summary, ulixertinib combined with adagrasib exhibited robust pre-clinical activity in a variety of xenograft models with KRASG12C and should be further evaluated.
- |||||||||| ulixertinib (BVD-523) / BioMed Valley Discoveries
CRISPR and drug screens identify ERK as the mediator of IFNg-induced melanoma growth inhibition (Section 23; Poster Board #14) - Mar 14, 2023 - Abstract #AACR2023AACR_2684; In live imaging experiments, we found that blocking ERK activity with the ERK inhibitor Ulixertinib blocks the induction of cell death after IFNg treatment in 17 of 23 (~74%) IFNg-sensitive PDM lines covering all the MAPK mutant and triple wildtype molecular subtypes of melanoma...This pathway is active in all melanoma subtypes, making it an attractive target to enhance IFNg GI in tumor cells. Our results provide a new understanding of the IFNg GI pathway that will also be crucial to define mechanisms of GI resistance in tumor cells.
- |||||||||| Biomarker, Enrollment closed, Metastases: NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) (clinicaltrials.gov) - Jan 4, 2023
P2, N=6452, Active, not recruiting, SARS-CoV-2-correlated ASGR1 is a novel marker that can be used for treating and identifying multiple human cancers. Recruiting --> Active, not recruiting
- |||||||||| ulixertinib (BVD-523) / BioMed Valley Discoveries
Preclinical, Journal: ERK Inhibitor Ulixertinib Inhibits High-Risk Neuroblastoma Growth In Vitro and In Vivo. (Pubmed Central) - Nov 27, 2022 Furthermore, ulixertinib potently inhibited NB tumor growth and prolonged the overall survival of the treated mice in two different NB mice models. Our preclinical study demonstrates that ulixertinib, either as a single agent or in combination with current therapies, is a novel and practical therapeutic approach for NB.
- |||||||||| ulixertinib (BVD-523) / BioMed Valley Discoveries
P1 data, Journal: Phase Ib Study of Ulixertinib Plus Gemcitabine and Nab-Paclitaxel in Patients with Metastatic Pancreatic Adenocarcinoma. (Pubmed Central) - Nov 26, 2022 P1 Our preclinical study demonstrates that ulixertinib, either as a single agent or in combination with current therapies, is a novel and practical therapeutic approach for NB. Ulixertinib plus GnP had similar frequency of grade ≥3 TRAEs and potentially efficacy as GnP, however was complicated by a high rate of all-grade TRAEs (ClinicalTrials.gov Identifier: NCT02608229).
- |||||||||| Ibrance (palbociclib) / Pfizer, ulixertinib (BVD-523) / BioMed Valley Discoveries
Enrollment open, Combination therapy, Metastases: Ulixertinib/Palbociclib in Patients With Advanced Pancreatic and Other Solid Tumors (clinicaltrials.gov) - Nov 22, 2022 P1, N=45, Recruiting, Ulixertinib plus GnP had similar frequency of grade ≥3 TRAEs and potentially efficacy as GnP, however was complicated by a high rate of all-grade TRAEs (ClinicalTrials.gov Identifier: NCT02608229). Active, not recruiting --> Recruiting
- |||||||||| Ibrance (palbociclib) / Pfizer, ulixertinib (BVD-523) / BioMed Valley Discoveries
Journal, Combination therapy: Combination Therapies with CDK4/6 Inhibitors to Treat KRAS-mutant Pancreatic Cancer. (Pubmed Central) - Nov 9, 2022 P1 Additionally, genes whose loss imparts a survival advantage were identified (e.g., RB1, PTEN, FBXW7), suggesting possible resistance mechanisms to CDK4/6 inhibition. In summary, this study has identified novel combinations with CDK4/6i that may have clinical benefit to PDAC patients.
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