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Article

The SOS1 Inhibitor BI 1701963 as Monotherapy or in Combination with Trametinib in Patients with KRAS Mutation-Positive Solid Tumors.

Clinical cancer research : an official journal of the American Association for Cancer Research - 3 Aug 2026

Jänne Pasi A, Johnson Melissa L, Li Jin, Pant Shubham, Dünzinger Ulrich, Ilia Luis, Möldner Kerstin, Soh Jae Eui, Yamamoto Noboru

Abstract excerpt

PURPOSE: BI 1701963 is a small-molecule son of sevenless 1 (SOS1) inhibitor that selectively binds to SOS1, blocking the protein-protein interaction of SOS1 with guanosine diphosphate-bound rat sarcoma virus (RAS) proteins [Kirsten RAS (KRAS), Harvey RAS, and neuroblastoma RAS], thereby inhibiting the growth of RAS-dependent cancer cells. PATIENTS AND METHODS: Three phase I dose-escalation studies evaluated BI...

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Identifiers

PMID: 42048384
DOI: 10.1158/1078-0432.CCR-25-3725
PMCID: PMC13430219

Genes

KRAS
SOS1

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026.

Related research

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Research trail→

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The SOS1 Inhibitor BI 1701963 as Monotherapy or in Combination with Trametinib in Patients with KRAS Mutation-Positive Solid Tumors.PMID 42048384Read ↗

SOS1: tracking the evolving path from promising to actionable therapeutic target in RAS-dependent cancers.Semantic proximity Read ↗

BI-3406, a Potent and Selective SOS1-KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition.Semantic proximity Read ↗

Targeted Degradation of SOS1 Exhibits Potent Anticancer Activity and Overcomes Resistance in KRAS-Mutant Tumors and BCR-ABL-Positive Leukemia.Semantic proximity Read ↗

Discovery of a potent and orally available SOS1 inhibitor with antitumor efficacy in KRAS-mutant colorectal cancers.Semantic proximity Read ↗

Combinations of RAS pathway inhibitors with targeted agents are active in spheroids of patient-derived cells with oncogenic KRAS variants from multiple cancer typesSemantic proximity Read ↗

Targeting Son of Sevenless 1: The pacemaker of KRAS.Semantic proximity Read ↗

SOS1 and KSR1 modulate MEK inhibitor responsiveness to target resistant cell populations based on PI3K and KRAS mutation status.Semantic proximity Read ↗

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Cereblon-based Bifunctional Degrader of SOS1, BTX-6654, Targets Multiple KRAS Mutations and Inhibits Tumor Growth.Semantic proximity Read ↗

Discovery of the First-in-Class Agonist-Based SOS1 PROTACs Effective in Human Cancer Cells Harboring Various KRAS Mutations.Semantic proximity Read ↗

Breaking Oncogene Addiction: Getting RTK/RAS-Mutated Cancers off the SOS.Semantic proximity Read ↗

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