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Zie ook in gerelateerde artikelen hiernaast of hieronder

12 november 2026: Bron: NEJM september 2026

Daraxonrasib (RMC-6236) geeft bij patiënten met eerder behandelde gevorderde niet-kleincellige longkanker met een KRAS mutatie alsnog opmerkelijk veel complete en gedeeltelijke remissies. Het percentage patiënten met een objectieve gedeeltelijke of complete remissie bedroeg 31% bij gebruik van Daraxonrasib (RMC-6236) in een dosering van 120 mg of minder, 34% bij doseringen van 160 tot 220 mg, en 37% bij een dosering van 300 mg. Dat blijkt uit een fase 1/2 doserings- en veiligheidsstudie bij totaal 136 patiënten met niet-kleincellige longkanker met een aangetoonde KRAS mutatie.

Bijwerkingen van graad 3 of hoger werden gerapporteerd bij 54% van de patiënten, waarbij longontsteking (bij 10%), diarree (bij 9%), huiduitslag (bij 8%) en bloedarmoede (bij 5%) bij ten minste 5% van de patiënten optraden; er deden zich vier bijwerkingen van graad 5 voor.

Een uitgebreidere studie bij patiënten met andere vormen van kanker met een KRAS mutatie is deze studie die oktober 2026 werd gepubliceerd:

KRAS Mutations in Cancers: From Undruggable Dilemma to Precision Medicine

met een grafische weergave van genoemde studies gekopieerd uit studieverslag. Abstract van deze studie waarvan het volledige studieverslag gratis is in te zien staat verderop in dit artikel:

graphic file with name MCO2-7-e71050-g002.webp

graphic file with name MCO2-7-e71050-g002.webp

De studie bij niet-kleincellige longkanker is gepubliceerd in het New England Journal of Medicine. Hier het abstract van de studie:

Daraxonrasib for Previously Treated RAS-Mutant Non–Small-Cell Lung Cancer

Authors: Kathryn C. Arbour, M.D., Salman Punekar, M.D., Jia Luo, M.D. https://orcid.org/0000-0003-3606-827X, Melissa Johnson, M.D., Alexander Spira, M.D., Ph.D., Benjamin Herzberg, M.D., Alexander Starodub, M.D., +13 , for the RMC-6236-001 Investigators*Author Info & Affiliations

Published September 2, 2026

N Engl J Med 2026;395:882-893

DOI: 10.1056/NEJMoa2504059

VOL. 395 NO. 9

Abstract

Background

RAS mutations, as a group, are the most common oncogenic drivers of non–small-cell lung cancer (NSCLC), and they occur in approximately 30% of patients. Whether daraxonrasib (RMC-6236) — an oral RAS(ON) multiselective, tri-complex inhibitor of guanosine triphosphate–bound mutant and wild-type RAS protein isoforms — is safe and effective in patients with RAS-mutant NSCLC is unknown.

Methods

In this phase 1–2, multicenter, dose-escalation and dose-expansion study of daraxonrasib, we enrolled patients with previously treated advanced RAS-mutant NSCLC and administered daraxonrasib in doses of 10 to 400 mg orally once daily in 21-day cycles. The primary end point was safety. Secondary end points included investigator-assessed objective response (complete or partial response) and the duration of response, with response assessed according to Response Evaluation Criteria in Solid Tumors, version 1.1.

Results

As of the data-cutoff date of July 21, 2025, a total of 136 patients with NSCLC who had been enrolled and treated with daraxonrasib at doses of 300 mg or less had been evaluated for safety and efficacy. Adverse events of any grade occurring with a dose of 300 mg or less, regardless of attribution, were reported in 99% of the patients, with rash, diarrhea, nausea, vomiting, and mucositis or stomatitis occurring in at least 30% of patients. Adverse events of grade 3 or higher were reported in 54% of the patients, with pneumonia (in 10%), diarrhea (in 9%), rash (in 8%), and anemia (in 5%) occurring in at least 5% of patients; four grade 5 adverse events occurred. The percentage of patients who had an objective response was 31% with daraxonrasib at a dose of 120 mg or less, 34% at doses of 160 to 220 mg, and 37% at a dose of 300 mg.

Conclusions

Among patients with previously treated metastatic RAS-mutant NSCLC receiving daraxonrasib at a dose of 300 mg or less daily, 54% had adverse events of grade 3 or higher, and antitumor activity was reported in more than 30%. (Funded by Revolution Medicines; RMC-6236-001 ClinicalTrials.gov number, NCT05379985.)

Cited by

KRAS Mutations in Cancers: From Undruggable Dilemma to Precision Medicine.
Cai J, Wu Y, Jia X, Yang L, Yang W, Lu W, Huang Z, Pan Y, Fei Z, Ru J, Zhao J, Shen J, Luo T, Chen D, Yu H, Deng H, Zeng J, Jiang W, Wu L.MedComm (2020). 2026 Oct 6;7(10):e71050. doi: 10.1002/mco2.71050. eCollection 2026 Oct.PMID: 42840361Free PMC article.Review.
Preliminary efficacy with daraxonrasib demonstrated in RAS-mutant NSCLC.
Romero D.Nat Rev Clin Oncol. 2026 Nov;23(11):826. doi: 10.1038/s41571-026-01207-1.PMID: 42749837No abstract available.

Hier het abstract van het studieverslag van vormen van kanker met een KRAS mutatie:

KRAS Mutations in Cancers: From Undruggable Dilemma to Precision Medicine

Jiaying Cai 1,#, Yimin Wu 2,#, Xing Jia 3,#, Li Yang 4, Wenjun Yang 4, Weishan Lu 5, Zhiye Huang 4, Yang Pan 5, Zixuan Fei 5, Junnan Ru 5, Jiazheng Zhao 3, Jue Shen 2, Taobo Luo 5, Da Chen 5, Haihong Yu 6, Haihan Deng 6, Jian Zeng 5,✉, Wenmei Jiang 3,✉, Leilei Wu 5,✉

PMCID: PMC13639538 PMID: 42840361

ABSTRACT

KRAS is one of the most frequently altered oncogenic drivers across human solid tumors and has long represented a central challenge in precision oncology. The clinical success of covalent KRAS G12C inhibitors has transformed a historically “undruggable” target into a tractable therapeutic class, but durable benefit remains limited by adaptive feedback, acquired resistance, co‐mutation context, and tumor‐lineage‐specific barriers. A major unresolved question is how to extend this success across diverse KRAS alleles and cancer types. This review summarizes the molecular epidemiology and therapeutic landscape of KRAS‐mutant cancers, with emphasis on non‐small cell lung cancer, colorectal cancer, and pancreatic ductal adenocarcinoma. We compare G12C‐directed therapy with emerging G12D‐, G12V‐, and pan‐KRAS strategies and dissect resistance architectures involving EGFR feedback, RTK/MAPK/PI3K pathway reactivation, phenotypic plasticity, stromal constraints, and immune or metabolic adaptation. We further discuss resistance‐informed combination therapy, targeted protein degraders, immune‐based approaches, antibody–drug conjugates, biomarker‐guided sequencing, and strategies for rare KRAS variants. Particular attention is given to how allele identity, tumor lineage, and adaptive signaling jointly shape therapeutic vulnerability. By framing KRAS therapy through the “same mutation, different outcomes” paradigm, this review provides a context‐informed roadmap for extending KRAS‐directed precision oncology beyond G12C monotherapy.

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