Neo-Bio-ADAURA: a Phase II Study to Evaluate Mechanisms of Resistance to Neoadjuvant Osimertinib

NCT06206850 | Recruiting Phase 2

• 1 other identifier: ESR-21-21629
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a single-arm phase II study of neoadjuvant osimertinib as monotherapy for the treatment of patients with resectable stage II-III non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) sensitizing mutation (L858R or deletion in exon 19 \[Ex19del\]).

Conditions

Non-squamous NSCLC

Keywords

NSCLC; Resectable; EGFR; stage II-III

Outcome Measures

Primary Outcomes (3)

• Identification of mechanisms of resistance to EGFR in surgical specimens

  Identification of mechanisms of resistance to osimertinib (alone or in combination with chemotherapy), based on assessment of the post-osimertinib surgical specimens.

  Up to approximately 5 years

• Frequency of various resistance mechanisms to EGFR

  The proportion of cells harbouring each mechanism within each tumour.

  Up to approximately 5 years

• Identify mechanisms of resistance to EGFR in surgical specimens

  Mechanisms that correlate with different levels of pathologic response.

  Up to approximately 5 years

Secondary Outcomes (6)

• Evaluate the efficacy of neoadjuvant osimertinib for resectable EGFR mutant NSCLC per rate of pathological complete response (pCR)

  Up to approximately 5 years

• Evaluate the efficacy of neoadjuvant osimertinib for resectable EGFR mutant NSCLC per major pathologic response (MPR)

  Up to approximately 5 years

• Rate of pathological downstaging

  Up to approximately 5 years

• Event-free survival (EFS defined as time to disease progression that precludes surgery, disease recurrence or death of any cause) of treated patients.

  Up to approximately 5 years

• Overall survival (OS) of treated patients

  Up to approximately 5 years

Study Arms (1)

neoadjuvant osimertinib

EXPERIMENTAL

Osimertinib 80 mg QD

Drug: Osimertinib

Interventions

Osimertinib DRUG

Oral Osimertinib 80 mg once daily (QD) for the duration of 9 weeks (3 cycles).

Also known as: Tagrisso

neoadjuvant osimertinib

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent for the trial prior to any study specific procedures. The subject must also provide consent for correlative translational study.
• Male or female subjects who are ≥18 years of age on the day of signing the informed consent.
• Histologically or cytologically documented non-squamous NSCLC with completely resectable (Stage II-III) disease.
• Note: thick needle biopsy of endobronchial ultrasound (EBUS)/bronchoscopy is acceptable.
• Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by a multi-disciplinary team evaluation (which should include a thoracic surgeon, specialised in oncologic procedures).
• Performance status (ECOG) 0-1 at enrolment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
• Lung function test results allowing curative surgery by thoracic surgeon's assessment.
• Cardiac function by ECHO cardiography results allowing curative surgery by thoracic surgeon's assessment.
• Have adequate normal organ and marrow function, including the following:
• Absolute neutrophil count ≥1.5×109/L.
• Platelet count ≥ 100×109/L.
• Haemoglobin ≥ 9.0 g/dL. Note: The use of granulocyte colony stimulating factor (G-CSF) support, platelet transfusion and blood transfusions to meet these criteria is not permitted.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal (ULN).
• Total bilirubin (TBL) ≤1.5 times the ULN or for patients with documented/suspected Gilbert's disease, bilirubin ≤2 times the ULN.
• Creatinine ≤1.5 times the ULN or creatinine clearance ≥50 mL/min (creatinine clearance can be measured or calculated by Cockcroft and Gault equation). If neoadjuvant chemotherapy is part of the neoadjuvant treatment regimen3, calculated creatinine clearance must be ≥60 mL/min.

You may not qualify if:

• Known active infection with hepatitis C virus (HVC) or tuberculosis. Patients positive for HCV antibody are eligible only if the polymerase chain reaction is negative for HCV RNA. Screening for chronic conditions is not required.
• Known active or uncontrolled infection with hepatitis B virus (HBV) (i.e., known positive HBV surface antigen \[HBsAg\] result).
• Participants with HBV infection may be included only if they meet all the following criteria:
• Demonstrated absence of HCV co-infection or history of HCV co-infection
• Demonstrated absence of HIV infection
• Participants with active HBV infection are eligible if they are:
• Receiving anti-viral treatment for at least 6 weeks prior to study treatment
• HBV DNA is suppressed to \<100 IU/mL
• transaminase levels are below ULN.
• Participants with a resolved or chronic infection HBV are eligible if they are:
• Negative for HBsAg and positive for hepatitis B core antibody \[anti-HBc IgG\].
• Receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment and 6-12 months (to be determined by a hepatologist) post-treatment or
• Positive for HBsAg, but for \>6 months have had transaminases levels below ULN and HBV DNA levels below \<100 IU/mL (i.e., are in an inactive carrier state).
• Receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment and 6-12 months (to be determined by a hepatologist) post-treatment.
• HIV active infection (e.g. patients receiving treatment for infection)

Sponsors & Collaborators

• Jair Bar, M.D., Ph.D.: lead

Study Sites (2)

Sheba Medical Center

Ramat Gan, Israel, 522651, Israel

RECRUITING

Sheba Medical Center, Jusidman Cancer Center

Ramat Gan, Israel, 5590000, Israel

RECRUITING

MeSH Terms

Interventions

osimertinib

Central Study Contacts

Sheba medical center

CONTACT

+972546288901; Jair.Bar@sheba.health.gov.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Deputy Director - Institute of Oncology. Head of Thoracic Oncology Unit

Model Details: Single arm

Study Record Dates

• First Submitted: December 19, 2023
• First Posted: January 16, 2024
• Study Start: February 19, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2030
• Last Updated: December 4, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

IL (2)