Efficacy study of osimertinib in treatment-naïve patients with EGFR mutant NSCLC according to TP53 mutational status (TEMPLE-2)

Phase 1

• Conditions: Patients with EGFR mutant NSCLC according to TP53 mutational status; MedDRA version: 20.0Level: LLTClassification code 10051054Term: Lung diseaseSystem Organ Class: 100000004855; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-001879-33-IT
• Lead Sponsor: FONDAZIONE POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI IRCCS UNIVERSITA' CATTOLICA DEL SACRO CUORE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-10-07
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 122

Inclusion Criteria

oProvision of informed consent prior to any study specific procedures.
oPatients (male/female) must be > 18 years of age.
oLocally advanced or metastatic EGFR mutant NSCLC, not amenable to curative surgery or radiotherapy with confirmation of the presence of EGFR exon 19 deletion or exon 21 p.L858R.
oMandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow central analysis.
oPatients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with osimertinib. Prior adjuvant and neo-adjuvant therapy is permitted (chemotherapy, radiotherapy) if at least 6 months has elapsed between the end of chemotherapy and enrolment.
oWorld Health Organization (WHO) performance status 0-2.
oPatients must have a life expectancy = 12 weeks.
oFemales should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
•Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.
•Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution.
•Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
oMale patients should be willing to use barrier contraception.
oPatient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
oAt least one lesion, not previously irradiated, that can be accurately measured at baseline as = 10 mm in the longest diameter (except lymph nodes which must have short axis = 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 22

Exclusion Criteria

•Subjects (sponsor and/or enrollment center staff) involved in planning and/or conducting the study
•Previous treatment with Osimertinib or any other anti-EGFR target drug
•Treatment with any other experimental drug in the previous 3 months of enrollment
•Patients who are currently being treated (or are unable to stop treatment before receiving the first dose of the experimental drug) with medications or homeopathic remedies included in Annex 6.
•Any residual toxicity from previous treatments that is grade > 1 at the time of enrollment, with the exception of alopecia. Grade 2 residual toxicity is permissible for platinum-related neuropathy
•Concomitant uncontrolled or severe systemic disease, including hypertension or haemorrhagic diathesis, active hepatitis B infection, hepatitis C or HIV
•Patients with spinal cord compression or symptomatic and / or unstable brain metastases. Corticosteroid therapy is allowed for the control of brain metastases as long as they are asymptomatic and treated with the same dosage for at least 14 days before starting treatment with Osimertinib
•Personal history of pulmonary interstitial disease, actinic pneumonia requiring corticosteroid therapy, or any evidence of active interstitial disease
•Any cardiac alteration between:
oCorrect QT interval (using Fredericia's formula)> 470 msec or the presence of risk factors that prolong the QT interval (electrolyte changes)
oAny clinically significant alteration of the rhythm, conduction or alterations of the resting ECG (e.g., complete left branch block).
•Inadequate blood chemistry values:
oAbsolute neutrophil count <1.5 x 109 / L.
oPlatelets <100 x 109 / L.
oHemoglobin <9 g / dL.
oAlanine aminotransferase and aspartate aminotransferase> 2.5 times the upper limit (ULN) in the absence of liver metastases> 5 times ULN in the presence of liver metastases
oTotal bilirubin> 1.5 times ULN in the absence of liver metastases or> 3 times ULN in the presence of Gilbert's syndrome (indirect hyperbilirubinemia) or liver metastases
oCreatinine> 1.5 times ULN concomitant with a creatinine clearance <50 ml / min (using the Cockcroft and Gault formula
•Refractory nausea or vomiting, or any gastrointestinal disease that does not allow the intake / absorption of osimertinib
•Second active neoplasms or previous treatments for other neoplasms for which at least 6 months have elapsed since the first day of Osimertinib therapy (or at least 2 years in case of bone marrow transplant)
•Patients with other medical conditions or serious clinical conditions, including those with uncontrolled active infection.
•History of hypersensitivity to osimertinib or to chemically similar drugs or to any excipient
•Women who are pregnant or breastfeeding
•Decision by the Investigator not to enroll the patient who is unable to comply with the procedures envisaged by the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the efficacy in terms of PFS of osimertinib in the treatment of patients with advanced EGFR mutant NSCLC, according to the TP53 mutational status.;Secondary Objective: To determine the efficacy in terms of OS of osimertinib in the treatment of patients with advanced EGFR mutant NSCLC, according to the TP53 mutational status.<br>To determine the activity in terms of ORR of osimertinib in the treatment of patients with advanced EGFR mutant NSCLC, according to the TP53 mutational status.;Primary end point(s): To determine the efficacy in terms of PFS of osimertinib in the treatment of patients with advanced EGFR mutant NSCLC, according to the TP53 mutational status.;Timepoint(s) of evaluation of this end point: PFS