A Phase 2 Study of Osimertinib and S-1 in Treatment Resistant EGFR Mutant NSCLC

NCT05773092 | Active Not Recruiting Phase 2

• 1 other identifier: 2022/2640
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to determine best overall response rate (BOR) based on radiological assessment per RECIST v1.1 to combination of S-1 and Osimertinib in treatment-resistant EGFR mutant lung cancer.

Conditions

NSCLC

Keywords

EGFR mutant lung cancer; Progression on Osimertinib

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  The efficacy of S-1 and Osimertinib. ORR is defined as the proportion of subjects who have best objective response (BOR) of CR or PR from start of combination treatment until disease progression or death due to any cause.

  Up to 2 years

Secondary Outcomes (3)

• Disease control rate (DCR)

  Up to 2 years

• Progression-free survival (PFS)

  Up to 3 years after end of treatment

• Overall survival (OS)

  Up to 3 years after end of treatment

Study Arms (1)

Intervention

EXPERIMENTAL

Oral S-1 + Oral Osimertinib

Drug: Oral S-1 + Oral Osimertinib

Interventions

Oral S-1 + Oral Osimertinib DRUG

S-1 (40mg) will be given orally twice a day (daily) from Day 1 to 14 (21 day cycle), and Osimertinib (80mg) will be given orally daily continuously.

Intervention

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed EGFR mutant NSCLC.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan, MRI, or calipers by clinical exam.
• Prior therapy: Patient with recurrent and/or metastatic EGFR mutant NSCLC, that has progressed on osimertinib as most recent line of treatment, and the primary doctor intends to continue with osimertinib treatment.
• Patients with no matched alterations (tumor or plasma) where clinical trials or approved systemic anti-cancer therapy are available, are eligible
• Patients with matched alterations on rebiopsy (tumor or plasma) who declined matching clinical trials, or approved systemic anti-cancer therapy, are eligible
• Age ≥21 years.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
• Patients must have adequate organ and marrow function as defined below:
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• total bilirubin ≤ institutional upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
• creatinine ≤ institutional ULN OR glomerular filtration rate (GFR) ≥50 mL/min/1.73 m2
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial provided that DDI with osimertinib has been addressed.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier (i.e., have residual toxicities \> Grade 1) with the exception of alopecia.
• Patients who are receiving any other investigational agents.
• Patients are excluded if they have symptomatic brain metastases or leptomeningeal metastases.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to S-1.
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations
• Pregnant women are excluded from this study because both compounds are potentially teratogenic.
• Subjects with concomitant second malignancies (except adequately treated non-melanomatous skin cancers, in situ cervical cancers, localized prostate cancer or in situ breast cancer) are excluded unless a complete remission was achieved at least 3 years prior to study entry and no additional therapy is required or anticipated to be required
• Prior organ allograft or allogeneic bone marrow transplantation
• Prisoners or subjects who are involuntarily incarcerated
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
• Inability to comply with restrictions and prohibited activities/treatments in this study.

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead
• Taiho Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

National Cancer Center Singapore

Singapore, 169690, Singapore

Location

MeSH Terms

Interventions

S 1 (combination); osimertinib

Study Officials

• Darren Wan-Teck Lim, MD

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2023
• First Posted: March 17, 2023
• Study Start: August 1, 2023
• Primary Completion: March 31, 2026
• Study Completion (Estimated): March 31, 2028
• Last Updated: September 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)