Osimertinib for NSCLC With Uncommon EGFR Mutations (UNICORN)

Uncommon EGFR Mutations: International Case Series on Efficacy of Osimertinib in Real-life Practice in First Line Setting

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.

Study Overview

• Status: Suspended
• Conditions: Carcinoma, Non-Small-Cell Lung; Genes, erbB-1
• Intervention / Treatment: Drug: Osimertinib

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 Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

Study Locations

• Israel
  • Ramat Gan, Israel, 5265601
    • Sheba Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Advanced NSCLC with uncommon EGFR mutation

Description

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)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	investigator-defined PFS	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
Overall survival	OS	From date of osimertinib initiation until date of death from any cause, assessed up to 100 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	RECIST-defined ORR	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
Brain response	RANO-BM	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
Adverse events on osimertinib	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
Time on treatment (TOT, on osimertinib)	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 to CNS progression	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
Mechanisms of resistance	Results of molecular tests done at time of progression on osimertinib (if done)	From date of osimertinib initiation until the date of molecular test performed after any documented progression, assessed up to 100 months

Collaborators and Investigators

• Sponsor: Sheba Medical Center
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Jair Bar, MD-PhD, Sheba Medical Center, Ramat Gan, Israel; Principal Investigator: Alfredo Addeo, MD, Geneva University Hospital, Geneva, Switzerland

Publications and helpful links

Helpful Links

• Initial results presented at ESMO 2021

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2020
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: March 30, 2022
• First Submitted That Met QC Criteria: June 14, 2022
• First Posted (Actual): June 16, 2022

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Osimertinib
• Other Study ID Numbers: UNICORN_226_13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No