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    Summary
    EudraCT Number:2022-002736-31
    Sponsor's Protocol Code Number:ETOP22-22
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-12-21
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2022-002736-31
    A.3Full title of the trial
    A multicentre, single-arm phase II trial of adagrasib in patients with KRASG12C-mutant NSCLC, including the elderly (=70 years) or patients with poor performance status
    Studio clinico multicentrico di fase II, a braccio singolo, di adagrasib sul NSCLC con mutazione del gene KRASG12C in pazienti anziani/e (=70 anni) o con performance status scarso
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of adagrasib for patients with KRASG12C-mutant non-small cell lung cancer, who are elderly or who are unwell because of their lung cancer.
    Studio su adagrasib contro il carcinoma polmonare non a piccole cellule con mutazione del gene KRASG12C in pazienti anziani/e o debilitati/e a causa della malattia.
    A.3.2Name or abbreviated title of the trial where available
    ADEPPT
    ADEPPT
    A.4.1Sponsor's protocol code numberETOP22-22
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorETOP IBCSG Partners Foundation
    B.1.3.4CountrySwitzerland
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMirati Therapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationETOP IBCSG Partners Foundation
    B.5.2Functional name of contact pointCoordinating Center
    B.5.3 Address:
    B.5.3.1Street AddressEffingerstrasse 33
    B.5.3.2Town/ cityBern
    B.5.3.3Post code3008
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number+41315119400
    B.5.5Fax number+41315119401
    B.5.6E-mailetop-regulatory@etop.ibcsg.org
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAdagrasib
    D.3.2Product code [MRTX849]
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAdagrasib
    D.3.9.1CAS number 2326521-71-3
    D.3.9.2Current sponsor codeMRTX849
    D.3.9.4EV Substance CodeSUB218270
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Patients with KRASG12C-mutant stage IV NSCLC that had prior chemotherapy and/or immune-checkpoint inhibition or both.
    Pazienti con NSCLC in stadio IV mutante KRASG12C precedentemente trattati con chemioterapia e/o inibizione del checkpoint immunitario o entrambi.
    E.1.1.1Medical condition in easily understood language
    Patients with 'non-small cell lung cancer' (NSCLC) that has grown again during/after previous treatment. A change (mutation) in a gene called KRAS was found, which causes the lung cancer to grow.
    Pazienti con "carcinoma polmonare non a piccole cellule" ricresciuto durante/dopo il trattamento. Il cambiamento (mutazione) nel gene chiamato KRAS, provoca la crescita del cancro ai polmoni.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10029515
    E.1.2Term Non-small cell lung cancer recurrent
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this trial is to assess the clinical efficacy of adagrasib treatment, in terms of objective response, in patients with KRASG12C-mutant NSCLC, including the elderly (=70 years) or patients with poor performance status (ECOG PS=2).
    L’obiettivo primario di questo studio è valutare l’efficacia clinica del trattamento con adagrasib in termini di risposta obiettiva, su pazienti affetti/e da NSCLC con mutazione di KRASG12C, inclusi i/le pazienti anziani/e (=70 anni) o con performance status scarso (ECOG PS=2).
    E.2.2Secondary objectives of the trial
    The secondary objectives refer to the evaluation of measures of clinical efficacy including durable clinical benefit (DCB), time-to-progression (TTP), progression-free survival (PFS), overall survival (OS), overall safety and patient-related outcomes.
    L’obiettivo secondario riguarda la valutazione di parametri relative all’efficacia clinica come i benefici clinici duraturi, il tempo di progressione, la sopravvivenza libera da progressione, la sopravvivenza complessiva, sicurezza generale e gli esiti correlate al paziente.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Histologically or cytologically confirmed stage IV NSCLC
    - KRASG12C-mutation by local testing (by tissue or ctDNA)
    - Prior treatment with at least one line of systemic therapy for NSCLC (e.g., platinum-based doublet chemotherapy and/or immune-checkpoint inhibition or both).
    - Life expectancy =12 weeks
    - Measurable disease according to RECIST v1.1
    - Age =18 years with ECOG PS 2 (cohort 1), or age =70 years with ECOG
    PS 0-1 (cohort 2)
    - Adequate haematological, renal and liver function
    - Negative pregnancy test for patients of childbearing potential
    - Ability to comply with the trial protocol, in the investigator's judgment.
    -Written informed consent for protocol treatment must be signed and dated by the patient and the investigator prior to any trial-related intervention, including the submission of mandatory biomaterial
    - NSCLC in stadio IV confermato istologicamente o citologicamente
    - Mutazione KRASG12C mediante test locale (su tessuto o ctDNA)
    - Precedente trattamento con almeno una linea di terapia sistemica per NSCLC (ad esempio, doppietta chemioterapica a base di platino e/o checkpoint immunitario inibizione o entrambi).
    - Aspettativa di vita =12 settimane
    - Malattia misurabile secondo RECIST v1.1
    - Età =18 anni con ECOG PS 2 (coorte 1) o età =70 anni con ECOG
    PS 0-1 (coorte 2)
    - Adeguata funzionalità ematologica, renale ed epatica
    - Test di gravidanza negativo per pazienti in età fertile
    - Capacità di rispettare il protocollo di prova, a giudizio dell'investigatore.
    -Il consenso informato scritto per il protocollo di trattamento deve essere firmato e datato dal paziente e dallo sperimentatore prima di qualsiasi sperimentazione correlata intervento, compresa la presentazione obbligatoria di biomateriale
    E.4Principal exclusion criteria
    -Prior investigational therapy within 28 days or at least 5 half-lives before enrolment
    -Prior treatment with an agent targeting KRASG12C
    -Leptomeningeal disease or untreated brain metastases:
    – Patient should be neurologically stable for at least 2 weeks before enrolment, without the need for corticosteroids, except for prednisone (or its equivalent) at a dose of =10 mg daily
    – For patients with definitively treated brain metastases, a minimum of 2 weeks must have elapsed from the last day of radiotherapy
    - History of intestinal disease or major gastric surgery likely to alter absorption of study treatment or inability to swallow oral medications.
    Any of the following cardiac abnormalities:
    – Unstable angina pectoris or myocardial infarction within 6 months prior to enrolment.
    – Symptomatic or uncontrolled atrial fibrillation within 6 months prior to enrolment.
    – Congestive heart failure =NYHA Class 3 within 6 months prior to enrolment.
    – Prolonged QTc interval >480 ms or family or medical history of congenital Long QT Syndrome
    -History of stroke or transient ischemic attack within 6 months prior to enrolment
    -Ongoing need for treatment with concomitant medication with any of the following characteristics: known risk of Torsades de Pointes; substrate of CYP3A with narrow therapeutic index; strong inducer of CYP3A and/or P-gp; strong inhibitor of BCRP; and proton pump inhibitors that cannot be switched to alternative treatment prior to enrolment
    -Known human immunodeficiency virus (HIV) infection
    -Acute or chronic hepatitis B or C infection. Note that the following are permitted:
    a. Patients treated for hepatitis C (HCV) with no detectable viral load at screening;
    b. Patients treated for HIV with no detectable viral load for at least 1 month prior to enrolment; and
    c. Patients with hepatitis B (HBV) receiving prophylaxis against reactivation of hepatitis B (either [HBsAg-positive with normal ALT and HBV DNA <2,000 IU/mL or <10,000 copies/mL] or [HBsAg-negative and anti-HBcAg-positive])
    -Women who are pregnant or in the period of lactation
    -Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study
    -Judgement by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
    - Precedente terapia sperimentale entro 28 giorni o almeno 5 emivite prima dell'arruolamento
    - Trattamento precedente con un agente mirato a KRASG12C
    -Malattia leptomeningea o metastasi cerebrali non trattate:
    - Il paziente deve essere neurologicamente stabile per almeno 2 settimane prima dell'arruolamento, senza necessità di corticosteroidi, ad eccezione del prednisone (o suo equivalente) a una dose di =10 mg al giorno
    – Per i pazienti con metastasi cerebrali definitivamente trattate, devono essere trascorse almeno 2 settimane dall'ultimo giorno di radioterapia
    - Storia di malattia intestinale o chirurgia gastrica maggiore che potrebbe alterare l'assorbimento del trattamento in studio o incapacità di deglutire farmaci per via orale.
    Una qualsiasi delle seguenti anomalie cardiache:
    - Angina pectoris instabile o infarto del miocardio entro 6 mesi prima dell'arruolamento.
    - Fibrillazione atriale sintomatica o incontrollata entro 6 mesi prima dell'arruolamento.
    - Insufficienza cardiaca congestizia =NYHA Classe 3 entro 6 mesi prima dell'arruolamento.
    – Intervallo QTc prolungato >480 ms o anamnesi familiare o medica di sindrome del QT lungo congenita
    -Storia di ictus o attacco ischemico transitorio entro 6 mesi prima dell'arruolamento
    - Necessità continua di trattamento con farmaci concomitanti con una delle seguenti caratteristiche: rischio noto di torsione di punta; substrato del CYP3A con indice terapeutico ristretto; forte induttore di CYP3A e/o P-gp; forte inibitore di BCRP; e inibitori della pompa protonica che non possono essere passati a un trattamento alternativo prima dell'arruolamento
    -Conosciuta infezione da virus dell'immunodeficienza umana (HIV).
    - Infezione acuta o cronica da epatite B o C. Si noti che sono consentiti:
    un. Pazienti trattati per epatite C (HCV) senza carica virale rilevabile allo screening;
    b. Pazienti trattati per HIV senza carica virale rilevabile per almeno 1 mese prima dell'arruolamento; Altro
    c. Pazienti con epatite B (HBV) sottoposti a profilassi contro la riattivazione dell'epatite B (o [HBsAg-positivi con ALT normali e HBV DNA <2.000 UI/mL o <10.000 copie/mL] o [HBsAg-negativi e anti-HBcAg-positivi] )
    -Donne in gravidanza o nel periodo dell'allattamento
    - Uomini e donne sessualmente attivi in ¿¿età fertile che non sono disposti a utilizzare un metodo contraccettivo efficace durante lo studio
    - Giudizio dello sperimentatore secondo cui il paziente non dovrebbe partecipare allo studio se è improbabile che il paziente rispetti le procedure, le restrizioni e i requisiti dello studio
    E.5 End points
    E.5.1Primary end point(s)
    Objective Response Rate (ORR) per RECIST v1.1, assessed at 12 weeks.
    Tasso di risposta obiettiva (ORR) secondo RECIST v1.1, valutato a 12 settimane.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Final analysis
    Analisi finale
    E.5.2Secondary end point(s)
    - Durable clinical benefit (DCB)
    - Time to progression (TTP)
    - Progression-free Survival (PFS)
    - Overall Survival (OS)
    - Safety
    - Patient-related outcomes
    - Beneficio clinico durevole (DCB)
    - Tempo di progressione (TTP)
    - Sopravvivenza libera da progressione (PFS)
    - Sopravvivenza globale (OS)
    - Sicurezza
    - Risultati relativi al paziente
    E.5.2.1Timepoint(s) of evaluation of this end point
    - DCB: final analysis
    - TTP: final analysis
    - PFS: final analysis
    - OS: final analysis
    - Safety: every 3 month and at final analysis
    -Patient-related outcomes: final analysis
    - DCB: analisi finale
    - TTP: analisi finale
    - PFS: analisi finale
    - OS: analisi finale
    - Sicurezza: ogni 3 mesi e all'analisi finale
    -Esiti correlati al paziente: analisi finale
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA23
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    France
    Spain
    Italy
    Belgium
    Ireland
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LPLV
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 34
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 34
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 53
    F.4.2.2In the whole clinical trial 68
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    none
    NA
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2023-03-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-01-19
    P. End of Trial
    P.End of Trial StatusOngoing
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