Astellas begins Phase III trial of setidegrasib in KRAS G12D mutated advanced lung cancer

Astellas has dosed the first patient in a Phase III study evaluating setidegrasib in previously treated patients with KRAS G12D mutated advanced non small cell lung cancer.

The study will compare the investigational treatment with docetaxel in patients with locally advanced unresectable or metastatic NSCLC whose disease has progressed during or after initial platinum based chemotherapy and checkpoint inhibitor treatment.

Setidegrasib is an investigational targeted protein degrader designed to selectively degrade and eliminate the KRAS G12D protein, which can drive tumour growth.

By removing the disease causing protein rather than simply blocking its activity, the therapy is intended to interfere with cancer signalling and promote destruction of tumour cells.

Around 5% of people with NSCLC are estimated to have a KRAS G12D mutation.

Although targeted treatments are available for several other molecularly defined forms of NSCLC, there are currently no therapies specifically approved for patients with KRAS G12D mutated disease.

Patients whose cancer progresses after initial treatment therefore continue to rely on systemic options such as chemotherapy.

The Phase III programme follows early clinical findings published in The New England Journal of Medicine in March 2026.

Those results demonstrated antitumour activity and a manageable safety profile for setidegrasib in patients with KRAS G12D mutated solid tumours.

Hidenori Kitai, MD, PhD, from the Department of Respiratory Medicine at Hokkaido University in Japan, said patients with KRAS G12D mutated NSCLC have historically had limited options once standard treatments stop working.

He said the Phase III study will help determine whether setidegrasib can provide a new targeted treatment approach for this molecularly defined group.

Tadaaki Taniguchi, MD, PhD, Chief Research and Development Officer at Astellas, said initiation of the trial marks continued progress in the development of setidegrasib.

He said the study will assess whether degrading KRAS G12D can address an important unmet need in patients with previously treated NSCLC.

The new trial is the second Phase III study of setidegrasib to begin within six months.

Astellas started another Phase III study in April 2026 evaluating the therapy in first line pancreatic ductal adenocarcinoma.

Setidegrasib is currently Astellas’ lead investigational targeted protein degrader.

The company is also continuing translational research into KRAS G12D driven cancers.

Astellas plans to present analyses from its Phase I study of setidegrasib in KRAS G12D mutated pancreatic ductal adenocarcinoma at the AACR Conference on Pancreatic Cancer.

The research will explore mechanisms associated with treatment response and resistance as well as potential combination strategies.

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Astellas, cancer research, clinical trials, lung cancer, NSCLC, Oncology, pharma news, precision oncology, Protein Degradation, setidegrasib, targeted therapy