KRAS G12C Inhibitor(BioArdis)(KRAS G12C Inhibitor(BioArdis)) - 药物靶点：KRAS G12C_在研适应症：KRAS G12C突变的实体瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名-

靶点

KRAS G12C

作用方式

抑制剂

作用机制

KRAS G12C抑制剂(KRAS G12C突变抑制剂)

治疗领域

肿瘤

在研适应症

KRAS G12C突变的实体瘤

非在研适应症-

原研机构

BioArdis LLC

在研机构

BioArdis LLC

非在研机构-

权益机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 KRAS G12C Inhibitor(BioArdis) 相关的临床结果

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100 项与 KRAS G12C Inhibitor(BioArdis) 相关的转化医学

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100 项与 KRAS G12C Inhibitor(BioArdis) 相关的专利（医药）

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26

项与 KRAS G12C Inhibitor(BioArdis) 相关的文献（医药）

2025-04-01·Clinical Pharmacology in Drug Development

Impact of Sotorasib, a KRAS G12C Inhibitor, on the Pharmacokinetics and Therapeutic Window of Digoxin, a P‐Glycoprotein Substrate

Article

作者: Houk, Brett ; Cardona, Panli

AbstractSotorasib is a small‐molecule Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C inhibitor indicated for the treatment of KRAS G12C‐driven cancers. KRAS G12C is a common mutation in solid tumors, including non‐small cell lung cancer. In vitro studies suggested that sotorasib is a weak inhibitor of P‐glycoprotein transporter. Digoxin is a known substrate for P‐glycoprotein. The primary objective of this study was to assess the impact of sotorasib on digoxin pharmacokinetics in healthy subjects. This Phase 1, open‐label, fixed‐sequence study enrolled 14 healthy subjects. Each subject received 0.5 mg of digoxin on Day 1 and 960 mg of sotorasib followed by 0.5 mg of digoxin on Day 7. Blood samples for digoxin pharmacokinetics were collected before dosing and up to 144 hours after the digoxin dose. Digoxin median time to maximum observed plasma concentration and mean terminal half‐life were similar following coadministration of digoxin with sotorasib compared with those of digoxin alone. Geometric mean digoxin area under the concentration‐time curve from time 0 extrapolated to infinity following coadministration of digoxin with sotorasib (40.3 h•ng/mL) was similar to that of digoxin alone (33.2 h•ng/mL). Geometric mean digoxin maximum observed plasma concentration following coadministration of digoxin with sotorasib (3.64 ng/mL) was higher compared with that of digoxin alone (1.90 ng/mL). Coadministration of digoxin and sotorasib did not impact sotorasib exposure. Single doses of 0.5 mg of digoxin were safe and well tolerated when administered alone or coadministered with 960 mg of sotorasib. Coadministration of digoxin with a single dose of sotorasib increased digoxin area under the concentration‐time curve from time 0 extrapolated to infinity and maximum observed plasma concentration by factors of 1.21 and 1.91, respectively, compared with digoxin alone.

2025-03-10·The Oncologist

Overcoming amplification-mediated resistance to sotorasib by dose re-escalation in KRAS G12C mutant NSCLC: a case report

Article

作者: Vita, Emanuele ; Vitale, Antonio ; Stefani, Alessio ; Cancellieri, Alessandra ; Bria, Emilio ; Lococo, Filippo ; Tortora, Giampaolo

AbstractPrecision oncology has transformed non-small cell lung cancer (NSCLC) treatment by tailoring therapies to the genomic profile of the disease, significantly improving clinical outcomes. However, acquired resistance to molecularly targeted therapies remains a major challenge. This report details a 69-year-old woman with KRAS G12C-mutant metastatic NSCLC who developed resistance to sotorasib, a KRAS G12C inhibitor. Initially responding to the standard dose of 960 mg, the patient required a dose reduction to 480 mg due to liver toxicity. After 20 months, oligoprogression occurred, managed through surgical resection. Molecular analysis of the resected tissue identified KRAS amplification as a resistance mechanism. Following disease progression, re-escalation of sotorasib to 960 mg led to renewed tumor response without additional toxicity. This case highlights dose re-escalation as a potential strategy to address resistance in selected patients and underscores the critical role of molecular profiling and personalized approaches in optimizing targeted NSCLC treatments.

2025-01-02·Future Oncology

Sotorasib for the treatment of locally advanced/metastatic non-small cell lung cancer

Review

作者: Carlisle, Jennifer W. ; Leal, Ticiana ; Gupta, Shruti ; Moniri, Nader H. ; Higgins, Jordyn P. ; Oduah, Eziafa I.

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is prognostic of poor survival for patients with non-small cell lung cancer (NSCLC). KRAS G12C mutations occur in 13% of NSCLC cases and despite the frequency of this mutation, advances in drug development against KRAS have historically been impeded due to the extremely high affinity of KRAS for guanosine triphosphate (GTP) and the lack of a binding pocket on the surface of KRAS that is suitable for drug binding. Sotorasib, a first-in-class, highly selective KRAS G12C inhibitor overcomes this issue by irreversibly binding in the switch-II pocket. Sotorasib was granted accelerated FDA approval for the treatment of KRASG12C-mutated locally advanced/metastatic NSCLC who have received at least one prior systemic therapy. This review summarizes the pharmacology, clinical efficacy, adverse effects, and clinical considerations of sotorasib.

2

项与 KRAS G12C Inhibitor(BioArdis) 相关的新闻（医药）

2024-04-08

·Endpoints

Medicxi backs Chinese biotech's next-gen KRAS G12C drug with $40M injection

The search for next-generation KRAS drugs that can do what Amgen and Bristol Myers Squibb’s medicines can’t has led to Medicxi’s first-ever investment in China. The European VC firm is pouring $40 million into Shanghai-based D3 Bio, whose KRAS G12C inhibitor is currently in Phase 2 trials for non-small cell lung cancer, colorectal cancer and pancreatic cancer. While Amgen and Mirati (which was acquired by Bristol Myers) made a major breakthrough by drugging KRAS G12C — a target long considered undruggable — physicians are still hoping for better drugs, said Francesco de Rubertis, co-founder and partner at Medicxi, in an interview with Endpoints News . In particular, he cited the need for longer duration of response, higher response rates, depth of response and CNS penetration of brain metastases.

临床2期并购

2023-08-24

·EndPoints

KRAS latecomer Roche draws cautious comparisons to Amgen, Mirati in early data

On a quest not just to catch up with, but leapfrog, Amgen and Mirati in the KRAS race, Roche has released early monotherapy data on its in-house candidate across a variety of cancers. Roche, which presented some divarasib data at the AACR conference in April, spelled out the most comprehensive set of results to date around the KRAS G12C inhibitor developed by Genentech in the New England Journal of Medicine . The Phase I study, published late Wednesday, featured a total of 137 patients with non-small cell lung cancer, colorectal cancer and other solid tumors. You’ll get access to free articles each month, plus you can customize what newsletters get delivered to your inbox each week, including breaking news.