Astellas Starts Phase 3 Study of Setidegrasib in Lung Cancer

Tokyo, Japan, September 24, 2026

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Setidegrasib is an investigational targeted protein degrader designed to selectively eliminate the KRAS G12D protein, a cancer-driving protein involved in abnormal signaling and tumor growth. Rather than simply inhibiting the activity of KRAS G12D, the drug is designed to recruit the cancer cell’s natural protein-degradation machinery to the disease-driving protein. This mechanism is intended to reduce the presence of KRAS G12D inside cancer cells and potentially disrupt signaling pathways that support tumor growth. KRAS mutations represent an important molecular driver across several cancers, while KRAS G12D is a specific mutation that occurs in a subset of patients with NSCLC and other solid tumors. Astellas stated that approximately 5% of people with NSCLC have a KRAS G12D mutation. Despite advances in targeted therapies for several other molecularly defined forms of lung cancer, there are currently no approved therapies specifically targeting KRAS G12D-mutated NSCLC, leaving patients who progress after standard treatment with limited targeted options.

Phase 3 Trial Will Compare Setidegrasib With Docetaxel

The new randomized, open-label Phase 3 study will compare setidegrasib with docetaxel, a chemotherapy treatment, in patients with KRAS G12D-mutated locally advanced or metastatic NSCLC whose disease has progressed following platinum-based chemotherapy and checkpoint inhibitor therapy. Astellas plans to enroll approximately 356 patients across multiple countries. The study’s dual primary endpoints are progression-free survival (PFS), assessed by blinded independent central review, and overall survival (OS). The study is registered as NCT07566052. Its design is intended to generate comparative evidence on whether the investigational targeted protein degrader can provide clinical benefit for patients whose disease has progressed after commonly used initial treatment approaches. Because setidegrasib remains investigational, its safety and efficacy for this use have not been established, and successful completion of the trial and regulatory review would be required before any potential approval for this indication.

Development Builds on Earlier Clinical Evidence

The Phase 3 program follows earlier clinical research evaluating setidegrasib in KRAS G12D-mutated solid tumors. Astellas said clinical findings published in The New England Journal of Medicine in March 2026 demonstrated antitumor activity and a manageable safety profile in patients with KRAS G12D-mutated advanced NSCLC and pancreatic cancer. These findings provided clinical evidence supporting continued investigation of the drug’s targeted protein-degradation approach. The NSCLC study follows another Phase 3 program initiated by Astellas in April 2026 evaluating setidegrasib in first-line pancreatic ductal adenocarcinoma (PDAC). Together, the programs are evaluating the investigational therapy across two major cancers in which KRAS G12D alterations are relevant to disease biology.

Astellas will also present translational analyses from its Phase 1 PDAC study at the AACR Conference on Pancreatic Cancer, examining mechanisms of response and resistance and potential combination strategies. For Astellas, the initiation of this Phase 3 NSCLC study represents another step in advancing targeted protein degradation as a potential therapeutic strategy in oncology. The ongoing trial will provide further evidence regarding setidegrasib’s clinical activity, safety, and potential role in patients with KRAS G12D-mutated advanced NSCLC. Future regulatory decisions will depend on the results of clinical development and subsequent assessment by health authorities.

Source: Astellas press release