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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 May 2022 → ongoing

Decision date (initial)

2024-12-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-517424-18-00

EudraCT number

2020-001879-33

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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.

Conditions and MedDRA coding

Patients with EGFR mutant NSCLC according to TP53 mutational status

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. o Provision of informed consent prior to any study specific procedures. o Patients (male/female) must be > 18 years of age. o Locally 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. o Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow central analysis. o Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with osimertinib. Prior adjuvant and neoadjuvant therapy is permitted (chemotherapy, radiotherapy) if at least 6 months has elapsed between the end of chemotherapy and enrolment. o World Health Organization (WHO) performance status 0-1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing. o Patients must have a life expectancy = 12 weeks. o Females 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 childbearing 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. o Male patients should be willing to use barrier contraception. o Patient 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. o At 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.

Exclusion criteria 1

1. 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 previous3months 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 Annex6,Any residual toxicity from previous treatments that is grade>1at the time of enrollment, with the exception of alopecia. Grade2 residual toxicity is permissible for platinum-related neuropathy,Concomitant uncontrolled or severe systemic disease, including hypertension or haemorrhagic diathesis, active hepatitisB infection, hepatitisC orHIV.Patients with HBV are only eligible for inclusion if they meet all the following criteria:Demonstrated absence of HCV co-infection or history ofHCVco-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,HBVDNA is suppressed to <100 IU/mL and transaminase levels are belowULN.Participants with a resolved or chronicHBVinfection are eligible if they are:Negative for HBsAg and positive for hepatitis B core antibody [anti-HBcIgG or total antiHBcAb]. In addition, patients must be receiving anti-viral prophylaxis for2-4 weeks prior to study treatment.or Positive for HBsAg, but for>6 months have had transaminases levels belowULNandHBVDNAlevels below<100IU/mL(are in an inactive carrier state).Patients must be receiving anti-viral prophylaxis for2-4weeks prior to study treatment.Patients with HIV are only eligible for inclusion if they meet all the following criteria:Demonstrated absence ofHBV/HCVco-infection,Undetectable viralRNA load for 6months,CD4+count of>350cells/µL,No history of AIDS-defining opportunistic infection within the past 12months,Stable for at least 4 weeks on the same anti-HIV medications,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 14days 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:Correct QT interval (using Fredericia's formula)>470 msec or the presence of risk factors that prolong the QT interval (electrolyte changes),Any clinically significant alteration of the rhythm, conduction or alterations of the restingECG(e.g., complete left branch block),Inadequate blood chemistry values:Absolute neutrophil count <1.5x109/L,Platelets <100x109/L,Hemoglobin <9g/dL,Alanine 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,Total bilirubin1.5timesULNin the absence of liver metastases or>3timesULNin the presence of Gilbert's syndrome (indirect hyperbilirubinemia) or liver metastases Creatinine>1.5timesULNconcomitant with a creatinine clearance<50ml/min (using theCockcroft andGault formula),Refractory nausea or vomiting, or any gastrointestinal disease that does not allow the intake absorption of Osimertinib,Second active neop or previous treat for other neop for which at least 6 months have elapsed since the first day of Osimertinib (or at least2 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,Wom who are pregnant or breastfeeding,Decision by the Inv not to enroll the patient who is unable to comply with the procedures envisaged by the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Sponsor organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Address

Largo Francesco Vito 1

City

Rome

Postcode

00168

Country

Italy

Scientific contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Emilio Bria

Public contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Emilio Bria

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications