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)

More details:

Overview

Sutetinib (also referenced as sutetinib maleate; development code SZMD4) is an investigational, oral, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor being developed for non–small-cell lung cancer (NSCLC) with non‑resistant, uncommon EGFR mutations, particularly G719X, S768I, and L861Q. Phase 2 studies are ongoing in the United States and China. (ascopubs.org)

Mechanism of action

Sutetinib is described as an irreversible EGFR TKI. A dedicated pharmacokinetic study in healthy volunteers identifies sutetinib and an active N‑oxide metabolite and characterizes it as an irreversible EGFR inhibitor; the study also evaluated food effects on exposure. While detailed kinase selectivity data have not been publicly reported, the clinical program targets tumors with uncommon activating EGFR mutations (G719X/S768I/L861Q), a subgroup where some third‑generation EGFR TKIs show variable activity. (pubmed.ncbi.nlm.nih.gov)

Efficacy

Human data to date come from a multicenter, open‑label phase 2a study reported at the 2023 ASCO Annual Meeting (Chinese registry CTR20190681). Thirty treatment‑naïve patients with advanced NSCLC harboring G719X, L861Q, S768I, or compound combinations of these mutations received sutetinib 80 mg (n=15) or 64 mg (n=15) once daily.

• Objective response rate (ORR): 71.4% (20/28 evaluable); 92.9% at 80 mg vs 50.0% at 64 mg.
• Disease control rate (DCR): 96.4% (100% at 80 mg; 92.8% at 64 mg).
• Median duration of response: 12.5 months (20.3 months at 80 mg; 9.2 months at 64 mg).
• One‑year overall survival: 84.7% (92.9% at 80 mg; 75.0% at 64 mg). Cutoff date for the analysis was January 15, 2022. (ascopubs.org)

Confirmatory and expansion studies are underway: - NCT06010329 (Phase 2, U.S.; start December 2023; estimated completion April 2026), single‑arm study in locally advanced/metastatic NSCLC with uncommon EGFR mutations; sponsor Teligene US. Sites include UC San Diego and MD Anderson. (clinicaltrials.ucsd.edu) - NCT05168566/Institutional listings (Phase 2b; U.S. and China; start September 2022; estimated completion June 2026). (fdaaa.trialstracker.net)

Safety

• In the ASCO 2023 phase 2a report (n=30), grade ≥3 treatment‑emergent adverse events occurred in 80.0% (80 mg) and 73.3% (64 mg). The most frequent grade ≥3 treatment‑related AEs were diarrhea (36.7%), abnormal liver function (13.3%), and rash (10.0%); one grade 4 hypokalemia event occurred (64 mg cohort). Investigators concluded toxicities were comparable to other EGFR TKIs. (ascopubs.org)
• A randomized crossover pharmacokinetic study in 18 healthy Chinese adults found that a high‑fat, high‑calorie meal modestly reduced sutetinib and metabolite exposure and delayed Tmax by ~2 hours; no serious adverse events were reported. (pubmed.ncbi.nlm.nih.gov)

Further reading

• Phase 2a ASCO abstract (efficacy and safety in uncommon EGFR‑mutant NSCLC). (ascopubs.org)
• Ongoing U.S. Phase 2 study NCT06010329 (trial overview and sites). (clinicaltrials.ucsd.edu)
• FDAAA TrialsTracker entry for NCT05168566 (Phase 2b; timelines and sponsor). (fdaaa.trialstracker.net)
• Pharmacokinetics/food‑effect study in healthy volunteers (Investigational New Drugs, 2024). (pubmed.ncbi.nlm.nih.gov)

Notes - No regulatory approvals have been announced as of October 7, 2025. Active interventional trials remain ongoing; reported efficacy is based on meeting‑abstract data and may evolve with full peer‑reviewed publications. (clinicaltrials.ucsd.edu)

Last updated: Oct 2025

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.