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A Phase I Study of Adagrasib and Durvalumab for Treatment of Advanced Non-small Cell Lung Cancers and Gastro-intestinal Cancers Harboring KRAS G12C Mutations

ABSTRACT: To find a recommended dose of the combination of adagrasib and durvalumab that can be given to patients with cancers that have a KRAS G12C mutation.

DISEASE(S): Gastrointestinal Neoplasms,Lung Cancer,Gastro-intestinal Cancer,Lung Neoplasms,Intestinal Neoplasms

PROVIDER: 59321 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Transcriptome profiling of NCI-H2030 cell line treated with adagrasib, K-975 and adagrasib+K-975

Project description:NCI-H2030 lines were seeded in 6-well plates in complete culture medium and cultured at densities allowing exponential growth: 50000 cells/well. After 24 h, compounds were added (DMOS, adagrasib (30 nM), K-975 (100 nM) and adagrasib (30 nM)+K-975 (100 nM)) at a final percentage of 0.2% DMSO. Twenty-four hours after compounds addition, cells were used for transcriptomic profiling.

2023-02-09 | GSE224439 | GEO

Adagrasib in Advanced Solid Tumors Harboring a KRASG12C Mutation.

Project description:PurposeAdagrasib, a KRASG12C inhibitor, has demonstrated clinical activity in patients with KRASG12C-mutated non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). KRASG12C mutations occur rarely in other solid tumor types. We report evaluation of the clinical activity and safety of adagrasib in patients with other solid tumors harboring a KRASG12C mutation.MethodsIn this phase II cohort of the KRYSTAL-1 study (ClinicalTrials.gov identifier: NCT03785249; phase Ib cohort), we evaluated adagrasib (600 mg orally twice daily) in patients with KRASG12C-mutated advanced solid tumors (excluding NSCLC and CRC). The primary end point was objective response rate. Secondary end points included duration of response, progression-free survival (PFS), overall survival, and safety.ResultsAs of October 1, 2022, 64 patients with KRASG12C-mutated solid tumors were enrolled and 63 patients treated (median follow-up, 16.8 months). The median number of prior lines of systemic therapy was 2. Among 57 patients with measurable disease at baseline, objective responses were observed in 20 (35.1%) patients (all partial responses), including 7/21 (33.3%) responses in pancreatic and 5/12 (41.7%) in biliary tract cancers. The median duration of response was 5.3 months (95% CI, 2.8 to 7.3) and median PFS was 7.4 months (95% CI, 5.3 to 8.6). Treatment-related adverse events (TRAEs) of any grade were observed in 96.8% of patients and grade 3-4 in 27.0%; there were no grade 5 TRAEs. TRAEs did not lead to treatment discontinuation in any patients.ConclusionAdagrasib demonstrates encouraging clinical activity and is well tolerated in this rare cohort of pretreated patients with KRASG12C-mutated solid tumors.

| S-EPMC10852394 | biostudies-literature

Combination of a SOS1-KRAS interaction inhibitor with a KRASG12C inhibitor combination can address intrinsic and acquired resistance leading to stronger and more durable response (Quant-Seq 2)

Project description:To investigate the transcriptomic changes associated with KRAS G12C inhibitor Adagrasib resistance and Adagrasib + SOS1 inhibitor (BI-3406) or Adagrasib + EGFR inhibitor (Cetuximab) combination treatment to overcome resistance. We performed differential gene expression analysis using RNA-seq generated from cell line derived xenograft (CDX) in vivo models. We compared different treatment conditions with DMSO treated condition.

2024-05-03 | GSE250032 | GEO

Combination of a SOS1-KRAS interaction inhibitor with a KRASG12C inhibitor combination can address intrinsic and acquired resistance leading to stronger and more durable response (Quant-Seq).

2024-05-03 | GSE225059 | GEO

Combination of a SOS1-KRAS interaction inhibitor with a KRASG12C inhibitor combination can address intrinsic and acquired resistance leading to stronger and more durable response [Tru-seq]

2024-05-03 | GSE255847 | GEO

Combination of a SOS1-KRAS interaction inhibitor with a KRASG12C inhibitor combination can address intrinsic and acquired resistance leading to stronger and more durable response (RNA-Seq).

2024-05-03 | GSE225060 | GEO

Targeting KRAS mutant cancers with a covalent G12C-specific inhibitor

Project description:We report RNAseq gene expression data following ARS-1620 treatment and shKRAS expressing cells (NCI-H358). We also compare gene expression changes following treatment with ARS-1620 or trametinib in NCI-H358, LU65 (KRAS-G12C+), and A549 (KRAS-G12S+) cells. Additionally we report a time course (4, 24, 48hr) of ARS-1620 and trametinib treated NCI-H358 cells.

2018-01-24 | GSE103021 | GEO

A Study of BMS-986466 With Adagrasib With or Without Cetuximab in Participants With Kirsten Rat Sarcoma Virus Glycine 12 to Cysteine (KRAS G12C)-Mutant Solid Tumors

Project description:The purpose of this study is to find a safe, tolerable, and efficacious dose of BMS-986466 when given orally, in combination with adagrasib with or without cetuximab in participants with advanced KRAS G12C-mutant non-small cell lung cancer (NSCLC), pancreatic duct adenocarcinoma (PDAC), biliary tract cancer (BTC), or colorectal cancer (CRC).

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Transcriptome profiling of NCI-H2030 cell line treated with adagrasib, K-975 and adagrasib+K-975

Project description:Transcriptome profiling of NCI-H2030 cell line treated with adagrasib, K-975 and adagrasib+K-975

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A Study of INCB099280 in Combination With Adagrasib in Adults With Advanced Solid Tumors Harboring a KRASG12C Mutation

Project description:The purpose of this study is to evaluate the safety and tolerability of INCB099280 in combination with adagrasib and to establish the MTD or identify RDE(s) for the combination of INCB099280 and adagrasib.

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