A Multicenter, Open-label, Phase 2 Study to Evaluate the Efficacy and Safety of Sutetinib Maleate Capsule in Locally Advanced or Metastatic NSCLC (Uncommon EGFR Mutations Only)

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Overview

Sutetinib is an investigational, orally administered, irreversible EGFR tyrosine-kinase inhibitor being developed for locally advanced or metastatic non-small-cell lung cancer (NSCLC) with uncommon, non-resistant EGFR mutations—principally G719X, S768I, and L861Q, including compound mutations. Clinical evidence currently comes from single-arm phase II studies; randomized comparative data have not been reported. (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

Sutetinib irreversibly inhibits mutant EGFR signaling, which promotes cancer-cell proliferation and survival. It is intended to target uncommon EGFR variants whose sensitivity to existing EGFR inhibitors can vary. (pubmed.ncbi.nlm.nih.gov)

Efficacy

In a multicenter, open-label phase IIb trial, 99 patients without prior EGFR-TKI treatment received sutetinib 80 mg once daily; 96 were evaluable for efficacy. At a median follow-up of 16.6 months:

• Independently reviewed objective response rate: 70.8% (95% CI, 60.7–79.7)
• Disease-control rate: 90.6%
• Median duration of response: 12.0 months
• Median progression-free survival: 13.7 months
• Median overall survival: not reached
• ORR was 84.4% with compound mutations and 64.1% with solitary uncommon mutations.

The study was non-randomized, so efficacy relative to other EGFR inhibitors remains uncertain. (pubmed.ncbi.nlm.nih.gov)

An earlier 30-patient phase IIa study reported an ORR of 71.4% among 28 evaluable patients, supporting selection of the 80-mg dose for further study. (asco.org)

Safety

In the phase IIb trial, treatment-related adverse events occurred in 97.0% of patients, with grade 3 or higher events in 42.4%. The most frequent grade 3 or higher treatment-related events were:

• Diarrhea: 28.3%
• Hypokalemia: 8.1%
• Increased gamma-glutamyl transferase: 5.1%

Dose reductions were required in 34.3%, and 4.0% discontinued treatment because of treatment-related toxicity. No treatment-related deaths were reported. (pubmed.ncbi.nlm.nih.gov)

Further reading

• Phase IIb trial publication in the Journal of Thoracic Oncology
• 2023 ASCO phase IIa abstract
• Phase IIb study record: NCT05168566
• Ongoing U.S. phase II study: NCT06010329

Last updated: Sep 2026

Inclusion Criteria:

1. Age 18 years old and above, male or female

2. Histopathological and/or cytopathological confirmation of locally advanced or metastatic NSCLC

3. Confirmation that the tumor harbors an uncommon epidermal growth factor receptor (EGFR) mutation (tumor tissue biopsy)

4. At least one measurable lesion

5. Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2

6. A minimum life expectancy of \> 3 months

7. Adequate bone marrow reserve, hepatic, renal, and coagulation function

Other inclusion criteria apply for participating in the study.

Exclusion Criteria:

1. Participant ever used the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR TKI) for anti-tumor therapy prior to enrollment (Cohort 1), or second generation EGFR TKI (Cohort 2)

2. Any systemic anti-tumor therapy such as chemotherapy and radiation therapy (including curative radiotherapy or spinal radiotherapy portion \>30%) used within 3 weeks prior to enrollment; immunotherapy within 4 weeks; any palliative radiotherapy for non-target lesions used to relieve symptoms and traditional Chinese medicines indicated for the tumor within 2 weeks prior to enrollment; Cohort 2: any EGFR TKIs within 5 half-lives.

3. Use or intake of drugs or foods containing potent inhibitors or inducers of cytochrome P450 isozyme 3A4 (CYP3A4) within 14 days or 5 half-lives, whichever is the longer, prior to enrollment

4. Surgical operation (excluding aspiration biopsy) of main organs or a significant injury within 4 weeks prior to enrollment

5. Any unresolved toxicities from prior therapy greater than National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAEv5.0) Grade 1, at the time of screening except for alopecia

6. Inability to swallow the study medication, any seriously (NCI-CTCAEv5.0 ≥ Grade 3) chronic gastrointestinal disorder, malabsorption syndrome or any other conditions with influence on gastrointestinal absorption

7. Active central nervous system metastases

8. Any active infection which has not been controlled at screening

Other exclusion criteria apply for participating in the Study.