Osimertinib for NSCLC With Uncommon EGFR Mutations

Suspended

• Conditions: Carcinoma, Non-Small-Cell Lung; Genes, erbB-1

• Registration Number: NCT05421936
• Lead Sponsor: Sheba Medical Center

Brief Summary

This is a multi-center, retrospective study of ucEGFRmut (exon 20 insertions excluded) metastatic NSCLC osimertinib-treated as first EGFR inhibitor. RECIST and RANO-BM brain objective response rate (ORR) were evaluated by investigators. mPFS, mOS and mDOR were calculated from osimertinib initiation. Mutations found at resistance were collected.

Detailed Description

The epidermal growth factor receptor ( EGFR) is the most common targetable driver in non-small cell lung cancer (NSCLC). Approximately 90% of the EGFR mutations include an exon 19 deletion and a L858R point mutation at exon 21. Less common mutations include, among others, G719X in exon 18, L861Q in exon 21, exon 20 insertions, S768I in exon 20, and T790M in exon 20. Osimertinib is an EGFR TKI that has been developed as non-competitive inhibitor targeting a range of EGFR mutant molecules, currently regarded as the first-line treatment of choice to EGFR mutant (EGFRm) patients. Inhibition of the less common EGFR mutant by osimertinib has been demonstrated.

Real-world data showed lower response rate (RR) and progression free survival (PFS) in patients harboring uncommon EGFR mutations compared to the ones with common mutations treated with EGFR TKIs. Osimertinib as treatment for patients with rare mutations has been assessed in a single arm phase II study in Korea. RR was 50%, PFS was 8.2 months, mOS was not reached. Osimertinib activity in patients with uncommon mutations was assessed also in a retrospective US study, time on treatment ranged from 7.7 months to 19.3 months.

This is a multi-centric, retrospective, real-world study. Study goal is to collect high quality data regarding the efficacy of osimertinib in TKI naive NSCLC patients with uncommon EGFR mutations. The primary endpoints are progression-free survival and overall survival, from osimertinib start. Secondary endpoints would be RECIST response, adverse events, time on treatment and time to CNS progression, CNS response and mechanisms of resistance if tested.

The study includes researchers from Belgium, Denmark, Israel, Switzerland, Netherlands, Germany, France, Italy and USA. Data collection will be conducted at each participating site, following ethics approval. No patient identifying information will leave each of the participating centers. Data will be collected centrally by the lead investigators and analyzed for the entire study cohort and for subgroups if deemed appropriate.

Study Timeline

• Study Start: 2020-09-27
• Study First Submitted: 2022-03-30
• Study First Submitted QC: 2022-06-14
• Study First Posted: 2022-06-16
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-20
• Last Update Posted: 2023-11-22
• Primary Completion: 2024-09
• Study Completion: 2024-09

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Age ≥ 18 years
2. NSCLC by histologic or cytologic diagnosis
3. Stage IV or stage III not amendable to curative treatment (i.e., advanced disease)
4. Uncommon mutation of EGFR (exon 20 insertion excluded)
5. Treated with osimertinib for advanced disease as first TKI
6. Osimertinib initiated not later than end of January 2021

Exclusion criteria:

1. Lack of any follow-up data
2. Lack of consent for data collection or ethics committee approval for the waiver of informed consent (i.e. for deceased patients)

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Progression free survival	From date of osimertinib initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months	investigator-defined PFS
Overall survival	From date of osimertinib initiation until date of death from any cause, assessed up to 100 months	OS

Secondary Outcome Measures

Name	Time	Method
Brain response	From date of osimertinib initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months	RANO-BM
Adverse events on osimertinib	From date of osimertinib initiation until 30 days after the date of last osimertinib treatment or date of death from any cause, whichever came first, assessed up to 100 months	Adverse events on osimertinib
Time to CNS progression	From date of osimertinib initiation until the date of first documented CNS progression or censured at last follow up or at date of death from any cause, whichever came first, assessed up to 100 months	Time to CNS progression
Overall response rate	From date of osimertinib initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months	RECIST-defined ORR
Time on treatment (TOT, on osimertinib)	From date of osimertinib initiation until the date of last osimertinib treatment or date of death from any cause, whichever came first, assessed up to 100 months	Time on treatment (TOT, on osimertinib)
Mechanisms of resistance	From date of osimertinib initiation until the date of molecular test performed after any documented progression, assessed up to 100 months	Results of molecular tests done at time of progression on osimertinib (if done)

Trial Locations

Locations (1)

Sheba Medical Centre; 🇮🇱 Ramat Gan, Israel