Browse
Submit Data
Databases
API
Help

Dataset Information

47 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Dose Escalation Study of HBI-2438 in Patients With Solid Tumors Harboring KRAS G12C Mutation

ABSTRACT: A Phase 1 dose escalation study in patients with advanced solid tumors harboring KRAS G12C mutation to determine the maximum tolerated dose and recommended Phase II dose of HBI-2438 and characterize its pharmacokinetic profile.

DISEASE(S): Lung Cancer,Solid Tumor,Colon Cancer,Colorectal Cancer,Cancer Of Pancreas,Non Small Cell Lung Cancer,Pancreatic Neoplasms,Lung Neoplasms,Cancer

PROVIDER: 2743980 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

ACCESS DATA

Json Xml

Similar Datasets

First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation

Project description:The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JNJ-74699157 in participants with advanced solid tumors harboring a kirsten rat sarcoma virus homolog (KRAS) glycine-to-cysteine (G12C) mutation (Part 1: Dose escalation) and to determine the safety and preliminary antitumor activity of JNJ-74699157 at the RP2D regimen in participants with advanced solid tumors harboring a KRAS G12C mutation (Part 2: Dose expansion).

| 2309880 | ecrin-mdr-crc

A Dose Escalation Study of SHP2 Inhibitor in Patients With Solid Tumors Harboring KRAS of EGFR Mutations

Project description:A Phase 1 dose escalation study in patients with advanced solid tumors harboring KRAS or EGFR mutations to determine the maximum tolerated dose and recommended Phase II dose of HBI-2376 and characterize its pharmacokinetic profile.

| 2398774 | ecrin-mdr-crc

Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation

Project description:This is Phase Ib/II, multicenter, open-label adaptive platform study of JDQ443 with select therapies in patients with advanced solid tumors harboring the KRAS G12C mutation.

| 2726548 | ecrin-mdr-crc

JAB-21822 Activity in Adult Patients With Advanced Solid Tumors Harboring KRAS G12C Mutation

Project description:This study is to evaluate the safety and tolerability of JAB-21822 monotherapy and combination therapy in adult participants with advanced solid tumors harboring KRAS G12C mutation.

| 2386408 | ecrin-mdr-crc

Expression data from mouse MLL/AF10(OM-LZ) myeloid leukemia cells harboring wild-type KRAS, KRAS-G12C, wild-type PTPN11, PTPN11-G503A, without or with Hoxa11

Project description:Cooperation of MLL/AF10 with RAS pathway mutations accelerated myeloid leukemia development. The detail molecular mechanism is analyzed by identification of the differentially expressed genes between MLL/AF10 cells harboring wild-type and mutant RAS pathway genes and by with or without Hoxa11. We used cDNA microarray to compare transcriptomes between mouse MLL/AF10 myeloid leukemia cells harboring wild-type KRAS and harboring KRAS-G12C (AKw1G and AK3G), or between MLL/AF10 cells harboring wild-type PTPN11 and harboring PTPN11-G503A (APw-1 and APm-1), or between MLL/AF10 cells without and with Hoxa11 (12G-V and 12G-H11).

2020-07-01 | GSE134586 | GEO

Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation

Project description:This is a phase Ib/II open label study. The escalation part will characterize the safety and tolerability of JDQ443 single agent and JDQ443 in combination with the other study treatments (TNO155 and tislelizumab) in advanced solid tumor patients. After the determination of the maximum tolerated dose / recommended dose for a particular treatment arm, dose expansion will assess the anti-tumor activity and further assess the safety, tolerability, and PK/PD of each regimen at the maximum tolerated dose / recommended dose or lower dose.

| 2363112 | ecrin-mdr-crc

Transcriptomic characterization of sotorasib-resistant tumors in Kras-G12C/Trp53-driven LUAD in genetically engineered mice

Project description:To characterize sotorasib resistance in lung adenocarcinomas (LUAD), we generated genetically engineered mice (Kras-G12C, Trp53-KO) and compared the transcriptional profiles of untreated and sotorasib-resistant tumors

2023-03-05 | GSE204752 | GEO

SHP2 Inhibition Abrogates Adaptive Resistance to KRAS-G12C-Inhibition and Remodels the Tumor Microenvironment of KRAS-Mutant Tumors

Project description:KRAS is the most frequently mutated oncogene in human cancer, and KRAS inhibition has been a longtime goal. Recently, inhibitors (G12C-Is) that bind KRAS-G12C-GDP and react with Cys-12 were developed. Using new affinity reagents to monitor KRAS-G12C activation and inhibitor engagement, we found that SHP2 inhibitors (SHP2-Is) increased KRAS-GDP occupancy, enhancing G12C-I efficacy. SHP2-Is abrogated feedback signaling by multiple RTKs and adaptive resistance to G12C-Is in vitro, in xenografts, and in syngeneic KRAS-G12C-mutant pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC) models. The combination of SHP2-I and G12C-I evoked favorable changes in the immune microenvironment, decreasing myeloid suppressor cells, increasing CD8+ T cells, and sensitizing tumors to PD-1 blockade. Experiments using an inhibitor-resistant SHP2 mutant showed that SHP2 inhibition in PDAC cells is required for tumor regression and remodeling of the immune microenvironment, but SHP2-Is also had direct effects on angiogenesis. Our results demonstrate that SHP2-I/G12C-I combinations confer a substantial survival benefit in PDAC and NSCLC and identify additional potential combination strategies. G12C-Is show significant, but limited, efficacy as single agents, in part because of “adaptive resistance”. We find that combining G12C-Is with SHP2-Is abrogates adaptive resistance and results in favorable changes in the immune microenvironment that potentiate PD-1 blockade in KRAS-mutant malignancies. SHP2-Is also can have direct, context-dependent, effects on tumor vasculature.

2020-10-01 | GSE149815 | GEO

Phase 1/2a Study of JAB-21822 Plus JAB-3312 in Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation

Project description:This is a multicenter, open-label phase 1/2a study consisting of two parts: dose escalation phase and dose expansion phase. The objective of the dose escalation phase is to evaluate the safety, tolerability and pharmacokinetics of JAB-21822 in combination with JAB-3312 in patients with advanced solid tumors harboring KRAS p.G12C mutation and to determine the RP2D for the combination therapy. In the dose expansion phase, preliminary efficacy and safety of the combination therapy at the RP2D will be further explored in patients with specific cancer harboring KRAS p.G12C mutation.

| 2710011 | ecrin-mdr-crc

Genome-Wide CRISPR Screen Identifies Multiple Synthetic Lethal Targets That Enhance KRAS (G12C) Inhibitor Efficacy [CRISPR]

Project description:KRAS G12C inhibitors (G12Ci) alone and in various combinations are being tested in multiple tumors with over-activation of the RAS/ERK pathway. KRAS plays a critical role in normal cell signaling; hence, G12Cis has been reported to create resistance. We found several novel pathways, including Hippo pathways, are enriched from significant dropouts upon MRTX849 treatment. Our results argue for testing KRAS G12C and TEAD inhibitor combinations in NSCLC patients.

2023-09-11 | GSE240110 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data