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

Recruiting now · Phase 2

Conditions studied: Non-squamous NSCLC

In brief

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 \[Ex19del\]).

Key facts

Study ID

NCT06206850

Run by

Jair Bar, M.D., Ph.D.

People needed

20

Starts

2024-02-19

Expected to finish

2030-01-01

Last updated by the study team

2024-12-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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.
• Body weight >30 kg.
• Life expectancy of >6 months prior to enrolment.
• A tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations (ie, T790M, G719X, S7681 and L861Q). Exon 20 insertion co-mutation are not permitted.
• Female patients who are not abstinent (in line with the preferred and usual lifestyle choice of the patient) and intend to be sexually active with a male partner must use highly effective contraceptive measures. Women of child-bearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required prior to the first dose of any study treatment if they are of child-bearing potential; or must have evidence of non-child-bearing potential by fulfilling 1 of the following criteria at screening:
• Post-menopausal, defined as 50 years of age or more and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments.
• Women under 50 years old would be considered as postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and have luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the institution.
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation (Further information is available in Appendix B (Definition of Women of Childbearing Potential and Acceptable Contraceptive Methods).
• Male patients must be willing to use barrier contraception.

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)
• Should participants with HIV infection be included, patients are only eligible if they meet all the following criteria:
• Undetectable viral RNA load for 6 months
• CD4+ count of >350 cells/μL
• No history of AIDS-defining opportunistic infection within the past 12 months'
• Stable for at least 4 weeks on the same anti-HIV medications
• Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically significant ILD.
• A history of another primary malignancy, except for the following:
• Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of osimertinib and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease.

Where it is running

• Sheba Medical Center — Ramat Gan, Israel, Israel (enrolling)
• Sheba Medical Center, Jusidman Cancer Center — Ramat Gan, Israel, Israel (enrolling)

Full record on ClinicalTrials.gov

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