| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| EGFR-mutated locally advanced or metastatic Non Small Cell Lung Cancer |
| carcinoma polmonare non a piccole cellule localmente avanzato o metastatico |
|
| E.1.1.1 | Medical condition in easily understood language |
| A specific type of lung cancer called "Non-Small Cell Lung Cancer" |
| un tumore chiamato "tumore polmonare non a piccole cellule" |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061873 |
| E.1.2 | Term | Non-small cell lung cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective is to assess the efficacy of the amivantamab and lazertinib combination, compared with osimertinib, in participants with EGFR mutation (Exon 19del or Exon 21 L858R substitution) positive, locally advanced or metastatic NSCLC |
| l'obiettivo primario e di valutare l'efficacia della combinazione di amivantamab e lazertinib paragonati con osimertinib, in partecipanti aventi la mutazione EGFR (esone 19del o la sostituzione dell'esone 21 L858R), e aventi un carcinoma polmonare non a piccole cellule localmente avanzato o metastatico |
|
| E.2.2 | Secondary objectives of the trial |
1. The clinical benefit achieved using the amivantamab and lazertinib combination compared with osimertinib in participants with EGFR mutation positive, locally advanced or metastatic NSCLC
2. The safety and tolerability of the amivantamab and lazertinib combination compared with osimertinib
3. The pharmacokinetics or immunogenicity for amivantamab and pharmacokinetics for lazertinib and assess their relationship to selected endpoints
4.The health-related quality of life and disease related symptoms in participants treated with the amivantamab and lazertinib combination compared with osimertinib
5. The efficacy of the amivantamab and lazertinib combination, compared with lazertinib monotherapy, in participants with EGFR mutation positive, locally advanced or metastatic NSCLC |
1. valutare il beneficio clinico ottento usando amivantamab e lazertinib in combinazione, comparandolo con osimertinib in partecipanti con un carcinoma polmonare non a piccole cellule localmente avanzato o metastatico positivo a EGFR
2 sicurezza e tollerabilità di amivantamab e lazertinib in combinazione, comparandolo con osimertinib
3. farmacocinetica e immunogenicità di amivantamab e la farmacocinetica per lazertinib e la valutazione della loro relazione a timepoint selezionati
4. la qualità della vita legata alla salute, e i sintomi legati alla malattia, in partecipanti trattati con la combinazione amivantamab e lazertinib paragonati a osimertinib
5. l'efficacia della combinazione di amivantamab e lazertinib, paragonata con la monoterapia di lazertinib, nel partecipanti con mutazione EGFR, e NSCLC metastatico o localmente avanzato |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. =18 years of age.
2. histologically or cytologically confirmed, locally advanced or metastatic NSCLC not amenable to curative therapy.
3. tumor that was previously determined to haveExon 19del or Exon 21 L858R substitution, as detected in an accredited local laboratory in accordance with local SOC. biopsy obtained at or after the diagnosis.
4. Unstained tumor tissue (sufficient to allow central analysis of EGFR mutation) and blood (for ctDNA, ddPCR, and pharmacogenomic analysis), both collected at or after the diagnosis
5. Any toxicities from prior anticancer therapy must have resolved
6. at least 1 measurable lesion, according to RECIST v1.1 not previously irradiated. Measurable lesions should not have been biopsied during screening,
7.adequate organ and bone marrow function asfollows, without history of red blood cell transfusion, platelet transfusion, or granulocyte colony stimulating factor (G-CSF) within 7
days prior to the date of the test.
8. ECOG status of 0 or 1
9. must sign an ICF (or their legally acceptable representative must sign)
10. A woman of childbearing potential must have a negative serum or urine pregnancy test at screening and within 72 hours of the first dose
11. A woman must be either of the following:
a. Not of childbearing potential
b. Of childbearing potential and
• practicing true abstinence during the entire period of the study,
• have a sole partner who is vasectomized;
• or practicing 2 highly effective methods of contraception, including 1 user independent method and a second method.
Participant must agree to continue contraception throughout the study and through 6 months after the last dose of study treatment.
12. A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study treatment.
13. A man must wear a condom during the study and for 6 months after receiving the last dose of study treatment. A man who is sexually active with a woman of childbearing potential must agree to
use a condom with spermicidal foam/gel/film/cream/suppository and his partner must also be practicing a highly effective method of contraception
If the participant is vasectomized, he must still use a condom (with or without spermicide) for prevention of passage of exposure through ejaculation, but his female partner is not required to use contraception.
14. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after receiving the last dose of study treatment.
15. Participant must be willing and able to adhere to the lifestyle restrictions specified in this protocol.
Full details of inclusion criteria can be found in section 5.1 of the study protocol. |
1. maggiore età legale
2. NSCLC metastatico o localmente avanzato, confermato istologicamente o citologicamente, non sensibile alla terapia curativa
3. tumore avente delezione dell'esone 19 o sostituzione L858R dell'esone 21, determinata da un laboratorio accreditato, biopsia ottenuta al momento della diagnosi o dopo;
4. tessuto tumorale (sufficiente per analisi per mutazione EGFR) e sangue (per ctDNA, ddPCR e analisi farmacogenomica) raccolti alla diagnosi o dopo la diagnosi
5. ogni tossicità precedente in reazione alla terapia anticancro deve essere risolta
6. almeno 1 lesione misurabile, in accordo al RECIST 1.1, non ancora irradiata. le lesioni misurabili non devono essere oggetto di biopsia durante lo screening
7. funzione do'organo e del midollo adeguata, senza storia di trasfusione di globuli rossi, piastrine, o fattori simolanti i granulociti, entro 7 gg prima del test
8. ECOG status di 0 o 1
9. deve firmare un consenso informato (o il suo rappresentante legale)
10. se donna in età fertile deve avere test di gravidanza negativo (siero o urine) entro 72 ore dalla prima dose
11. una donna deve non essere in età fertile; se lo è deve: praticare astinenza, avere un solo partner vasectomizzato, praticare 2 sistemi efficaci di contraccezione
devono concordare di proseguire la contraccezione per 6 mesi dall'ultima dose di trattamento
12. una donna non deve donare oociti per la riproduzione assistita fino a 6 mesi dall'ultima dose di trattamento
13. un uomo deve usare il preservativo; se sessualmente attivo con una donna in età fertile, deve usare il preservativo con pomata spermicida e la partner deve utilizzare metodi efficaci di contraccezione:
14. un uomo non deve donare sperma per la riprouduzione asistita;
15.i participanti devono scegliere volontariamente di aderire alle restrizioni specificate nel protocollo
dati completi nella sezione 5.1 del protocollo di studio |
|
| E.4 | Principal exclusion criteria |
1. received any prior systemic treatment for locally advanced or metastatic disease (adjuvant or neoadjuvant allowed, if administered more than 12 months prior to the development of locally advanced or metastatic disease).
2. Participant has symptomatic brain metastases.
3. Participant has an active or past medical history of leptomeningeal disease.
4. Participant has spinal cord compression that has not been definitively treated with surgery or radiation or requires steroid treatment within 2 weeks prior to randomization.
5. Participant has uncontrolled tumor-related pain.
6. Participant has an active or past medical history of ILD/pneumonitis, including drug-induced or radiation ILD/pneumonitis.
7. Participant has an uncontrolled illness
8. Participant has an active malignancy other than the disease being treated under study
9. Participant has active cardiovascular disease
10. Participant has known allergy, hypersensitivity, or intolerance to the excipients used in formulation of amivantamab, lazertinib, or osimertinib, or any contraindication to the use of osimertinib.
11. Participant is currently receiving medications or herbal supplements known to be potent CYP3A4/5 inhibitors or inducers and is unable to stop use for an appropriate washout period prior to randomization.
12. Participant has received any prior treatment with an EGFR TKI.
13. Participant has received an investigational medication within 12 months before randomization or is currently enrolled in an investigational study.
14. Participant is pregnant, breast-feeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment.
15. Participant plans to father a child while enrolled in this study or within 6 months after the last dose of study treatment.
16. Participant has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit,
or confound the protocol-specified assessments
17. Participant has at Screening:
• Positive hepatitis B (hepatitis B virus [HBV]) surface antigen (HBsAg)
• Positive hepatitis C (hepatitis C virus [HCV]) antibody (anti-HCV)
• Other clinically active infectious liver disease
18. Participant is positive for human immunodeficiency virus (HIV)
19. Participant had major surgery (eg, requiring general anesthesia), excluding placement of vascular access or tumor biopsy, or had significant traumatic injury within 4 weeks before signing the ICF, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study.
Note: Participants with planned surgical procedures to be conducted under local anesthesia may participate.
Full details of exclusion criteria can be found in section 5.2 of the study protocol. |
1. esclusi trattamenti sistemici per tumori localmente avanzati o metastatici (adiuvanti e neoadiuvanti ammessi, se somministrati 12 mesi prima dell'evoluzione)
2, metastasi cerebrali sintomatiche
3. storia di malattia leptomeningeale
4. compressione della colonna non trattata con chirurgia o radiazione o che richiedono trattamenti di steroidi entro 2 settimane dalla randomizzazione
5. dolore non controolato legato al tumore
6. storia clinica di IDL/polmonite (o patologia attiva) inclusa se causata da farmaci o radiazioni
7. malattia non controllata
8. altro tumore maligno
9. malattie cardiovascolari
10. allergia, intolleranza o ipersensibilità agli eccipienti delle forme farmaceutiche, o controindicazioni all'uso di osimertib
11. medicine a base di erbe potenzialmente inibenti o inducenti CYP3A4/5 (e impossibilità per i partecipanti di fare adeguato washout prima della randomizzazione)
12. trattamenti pregressi con inibitori delle tirosin kinasi
13. somministrazione di altro IMP entro 12 mesi, o concomitante arruolamento in un altro studio
14. gravidanza, allattamento, o pianificazione di gravidanza entro 6 mesi dall'ultima dose di farmaco
15. i partecipanti maschi devono pianificare una paternità dopo 6 mesi dall'ultima dose di farmaco
16. condizione che, a giudizio del PI, possa andare contro il bene del paziente qualora questi partecipasse allo studio
17. partecipanti con allo screening: epatite B, epatite C, altre malattie infettive epatiche
18. HIV positivo
19. soggetti che hanno avuto chirurgia in anestesia totale, escludendo accesso vascolare e biopsia tumorale, o hanno avuto trauma entro 4 settimane prima della firma del consenso, o non si sono ripresi del tutto dalla chirurgia o hanno un intervento pianificato surante lo studio
maggiori dettagli nella sezione 5.2 del protocollo di studio |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression-free survival (PFS) according to RECIST v1.1 by blinded independent central review |
| PFS in accordo al RECIST 1.1 su valutazione di un revisore centrale in cieco |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| A futility analysis based on PFS will be conducted when approximately 150 PFS events have occurred overall (all treatment arms combined). |
| analisi di futilità dopo 150 PFS (su tutti i bracci di studio) |
|
| E.5.2 | Secondary end point(s) |
Arm A vs Arm B:
1. Overall survival
2. Objective response rate
3. Duration of response
4. PFS after first subsequent therapy (Arm A vs Arm B)
5. Time to symptomatic progression
6. Intracranial PFS
7. Incidence of severity of adverse events and clinical laboratory abnormalities, assessment of vital signs, and physical examination abnormalities
8. Serum amivantamab and lazertinib concentrations, and antiamivantamab antibodies
9. NSCLC-SAQ
10. EORTC-QLQ-C30
Arm A vs Arm C:
11. PFS
12. Overall survival |
braccio A VS braccio B
1. overall survival
2. tasso di risposta
3. durata della risposta
4. PFS dopo la prima terapia successiva
5. tempo alla progressione sintomatica
6. PFS intracranica
7. incidenza degli eventi avversi e anormalità cliniche, valutazione dei segni vitali, e anormalità ad esame fisico
8. concentrazioni seriche di amivantamab e lazertinib, e di anticorpi anti avimantamab
9. NSCLC-SAQ
10. EORTC-QLQ-C30
Braccio A VS braccio C
11. PFS
12. Overall survival |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| From randomization until the date of objective disease progression or death,whichever comes first |
| dalla randomizzazione fino alla data della progressione, o della morte |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Tolerability, Immunogenicity, Quality of Life and Biomarker evaluation |
| tollerabilità, immunogenicità, qualità della vita e valutazione biomarker |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 62 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Belarus |
| Brazil |
| Canada |
| China |
| Hong Kong |
| India |
| Israel |
| Japan |
| Korea, Republic of |
| Malaysia |
| Mexico |
| Philippines |
| Russian Federation |
| Singapore |
| Taiwan |
| Thailand |
| Turkey |
| Ukraine |
| United States |
| Belgium |
| France |
| Germany |
| Hungary |
| Italy |
| Netherlands |
| Poland |
| Portugal |
| Spain |
| United Kingdom |
|
| E.8.7 | Trial 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
|
| 5 years |
| 5 anni dall'inizio |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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