| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Non Small Cell Lung cancer |
| Cancro del polmone non a piccole cellule |
|
| E.1.1.1 | Medical condition in easily understood language |
| Non Small Cell Lung cancer |
| Cancro del polmone 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 | 10059515 |
| E.1.2 | Term | Non-small cell lung cancer metastatic |
| 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 |
1. To compare MK-7684A + docetaxel to normal saline placebo + docetaxel with respect to Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR)
2. To compare MK-7684A to normal saline placebo + docetaxel with respect to PFS per RECIST 1.1 as assessed by BICR
|
1. Confrontare MK-7684A+docetaxel con placebo+docetaxel rispetto alla sopravvivenza libera da progressione (PFS) valutata mediante revisione centrale
indipendente in cieco (BICR) secondo i criteri di valutazione della risposta nei tumori solidi 1.1 (RECIST 1.1)
2. Confrontare MK-7684A con placebo+docetaxel rispetto alla sopravvivenza libera da progressione (PFS) secondo RECIST 1.1 valutato mediante BICR |
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate Objective Response Rate (ORR) in participants treated with MK-7684A +docetaxel, MK-7684A, or normal saline placebo + docetaxel per RECIST 1.1 by BICR
2. To evaluate Overall Survival (OS) in participants treated with MK-7684A + docetaxel, MK-7684A, or normal saline placebo + docetaxel
3. To evaluate Duration of Response (DOR) per RECIST 1.1 as assessed by BICR in participants treated with MK-7684A + docetaxel, MK- 7684A, or normal saline placebo + docetaxel
4. To evaluate the safety and tolerability in participants treated with MK-7684A + docetaxel, MK-7684A, or normal saline placebo + docetaxel. |
1. Valutare il tasso di risposta obiettiva (ORR) nei partecipanti trattati con MK-7684A + docetaxel, MK-7684A o placebo+docetaxel secondo RECIST 1.1 valutato mediante BICR
2. Valutare la sopravvivenza globale (OS) nei partecipanti trattati con MK-7684A+docetaxel, MK-7684A o palcebo+ docetaxel
3. Valutare la durata della risposta (DOR) secondo RECIST 1.1 valutato mediante BICR nei partecipanti trattati con MK-7684A+docetaxel, MK- 7684A, o placebo+docetaxel
4. Valutare la sicurezza e la tollerabilità nei partecipanti trattati con MK-7684A+docetaxel, MK-7684A o placebo+docetaxel |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Has a histologically or cytologically confirmed diagnosis of metastatic NSCLC (Stage IV: M1a, M1b, M1c, AJCC Staging Manual, version 8).
2. Has confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as primary therapy.
3. Has PD on treatment with one prior anti-PD-1/PD-L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies.
4. Has PD as determined by the investigator after platinum doublet chemotherapy for metastatic disease.
5. Has measurable disease based on RECIST 1.1, as determined by the local site assessment.
6. Has provided tumor tissue for PD-L1 biomarker analysis from an archival sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
7. Is male or female, >=18 years of age at the time of providing documented informed consent.
8. Has a life expectancy of at least 3 months.
9. Has an ECOG Performance Status of 0 to 1 assessed within 7 days prior to randomization.
10. Male participants randomized to docetaxel are eligible to participate if they agree to the following during the intervention period and for at least 180 days after the last dose of docetaxel:
• Refrain from donating sperm
PLUS either:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent.
OR
• Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below:
o Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant.
o Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
11. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a WOCBP
OR
• Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
• A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention.
• A WOCBP randomized to docetaxel is eligible to participate if she is using a contraceptive method that is highly effective with low user dependency or is abstinent from heterosexual intercourse as her preferred and usual lifestyle and agrees not to donate or freeze/store eggs during the intervention period and for at least 180 days after the last dose of docetaxel.
• If a urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
12. The participant (or legally acceptable representative if applicable) provides written informed consent for the study.
13. Has adequate organ function. Specimens must be collected within 10 days before the start of study intervention. |
1.Ha diagnosi di NSCLC confermata istolog o citolog (Stadio IV:M1a,M1b,M1c del manuale di stadiazione dell’AJCC,v.8)
2.Ha conferma che le terap anti-EGFR,anti-ALK o anti-ROS1 non sono indicate come terap 1°aria
3.Ha mostrato una PD durante un prec trattam con un mAb anti-PD-1/PD-L1 somminist in monoterap o in associaz ad altri inibitori di checkpoint o ad altre terap
4.Ha PD determinata dallo speriment dopo essere stato sottoposto a doppietta chemioter a base di platino per la malattia metastatica
5.Ha malattia misurabile con i criteri RECIST 1.1,determinata dalla valutazione del centro locale
6.Ha fornito un camp di tes tumorale per l’analisi del biomarc PD-L1 presente in archivio o una biopsia incisionale o escissionale di una lesione tumorale non irradiata in prec di nuova acquisiz
7.È un sog di sesso maschile o femminile di età >=18 anni alla consegna del consenso informato
8.Ha un’aspettativa di vita pari ad almeno 3 mesi
9.Ha un performance status ECOG pari a 0 o 1,valutato nei 7gg prec la random
10.I partecip di sesso maschile random a ricevere docetaxel sono idonei a partecip se acconsentono a quanto segue durante il periodo di trattam sperim e per almeno 180 gg dopo l’ultima dose di docetaxel:
•Astenersi dal donare sperma PIÙ
•Non avere rapporti eterosex come stile di vita preferito e abituale (astinenza a lungo termine e persistente) e accettare di astenersi da tali rapporti
O
•Acconsentire a utilizzare un metodo contrac, a meno che non sia confermata l’azoospermia (in seguito a vasectomia o secondaria a cause mediche come specificato di seguito:
o Acconsentire a utilizzare un profilattico maschile e a far utilizzare alla partner un metodo contrac aggiuntivo in caso di rapporti sex penetrativi vaginali con una WOCBP
o Gli uomini con una partner incinta o che allatta al seno devono acconsentire ad astenersi dai rapporti sex penetrativi vaginali o a utilizzare un profilattico maschile durante ogni rapporto di questo tipo
11.Le pz di sesso fem sono idonee alla partecip se non sono in gravidanza o in allattam, e se almeno una delle condiz indicate di seguito risulta applicabile:
•Non essere una WOCBP
O
•Essere una WOCBP e utilizzare un metodo contrac altamente efficace (con un tasso di fallimento <1% all’anno), con scarsa dipendenza dall’utilizzatore, o non avere rapporti eterox come stile di vita preferito e abituale (astinenza a lungo termine e persistente), durante il periodo di trattam sperim e per almeno 120gg dopo l’ultima dose di trattam. Lo speriment deve valutare la possibilità di fallimento del metodo contrac (mancata compliance, inizio recente) in relaz alla 1° dose del trattam sperim
•Le WOCBP devono avere esito neg al test di gravidanza ad alta sensibilità (eseguito su urine o siero secondo quanto stabilito dai regolamenti locali) nelle 24h (per il test su urine) o 72h (per il test su siero) che precedono la 1° dose del trattam sperim
•Le WOCBP random a ricevere docetaxel sono elegibili a partecip se utilizzano un metodo contrac altamente efficace con scarsa dipendenza dall’utilizzatore o se si astengono dall’avere rapporti eterosex come stile di vita preferito e abituale e se acconsentono a non donare ovuli né a congelarli/conservarli durante il periodo di trattam sperim e per almeno 180gg dopo l’ultima dose di docetaxel
•Se non può essere confermata la negatività del test sulle urine è nec eseguire un test di gravidanza su siero.In tali casi, la pz deve essere esclusa dalla partecipaz se il test su siero risulta pos
•Lo speriment è responsabile dell’analisi dell’anamnesi medica,mestruale e dell’attività sex recente finalizzata a ridurre il rischio di genotossicità di inclusione nello studio di una donna in gravidanza allo stadio iniziale non rilevata
12.Il sog (o il rappresentante legalmente accettabile, se applicabile) fornisce il consenso informato scritto per lo studio
13.Presenta funzionalità d’organo adeguata. Si dovrà procedere al prelievo dei campioni nei 10 gg prece l’inizio del trattam sperim |
|
| E.4 | Principal exclusion criteria |
1. Has known active or untreated CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression) for at least 4 weeks by repeat imaging, clinically stable, and without requirement of steroid treatment for at least 7 days before the first dose of study intervention.
2. Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy.
3. Has received docetaxel as monotherapy or in combination with other therapies.
4. Has received previous treatment with another agent targeting the TIGIT receptor pathway.
5. Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
6. Has received radiotherapy within 2 weeks of start of study intervention.
7. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
8. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
9. Has severe hypersensitivity (>=Grade 3) to docetaxel or MK-7684A and/or any of its excipients.
10. Has an active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy is not considered a form of systemic treatment and is allowed.
11. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention.
12. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
13. Has a known history of interstitial lung disease. Lymphangitic spread of the NSCLC is not exclusionary.
14. Has an active infection requiring systemic therapy.
15. Has a known history of HIV infection.
16. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
17. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
18. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
19. If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery before starting study intervention.
20. Has had an allogenic tissue/solid organ transplant. |
1.Presenta metastasi al SNC attive o non trattate note e/o meningite carcinomatosa. I partecip con metastasi cerebrali trattate prec possono partecipare,purché siano radiologicam stabili (ossia,senza evidenza di progressione) da almeno 4 sett agli esami di imaging ripetuti,siano clinicamente stabili e non richiedano il trattam con steroidi almeno nei 7gg prec la 1° dose di trattam sperim
2.Ha anamnesi nota di un’ulteriore neoplasia maligna,eccetto se il partecip è stato sottoposto a una terap potenzialm curativa senza evidenza di recidiva della malattia per almeno 3 anni dall’inizio di tale terap
3.Ha ricevuto docetaxel in monoterap o in associazione ad altre terap
4.Ha ricevuto un prec trattam con un altro agente che colpisce la via del recet TIGIT
5.Ha ricevuto una prec terap antitumor sistemica tra cui agenti sperim nelle 4 sett prec la randomiz
6.Ha ricevuto radioterap nelle 2 sett preci l’inizio del trattam sperim
7.È stato vaccinato con vaccino vivo o vivo attenuato nei 30gg prec la 1°dose del trattam sperim.La somministr di vaccini con virus inattivati è ammessa
8.Partecipazione attuale o pregressa a uno studio su un farmaco sperim o utilizzo di un dispositivo sperim nelle 4 sett prec la 1°dose del trattam in studio
9.Ha ipersensibilità grave (grado >=3) a docetaxel o MK-7684A e/o a uno qualsiasi degli eccipienti
10.Presenta malattia autoimmune attiva che ha richiesto il trattam sistemico negli ultimi 2 anni. La terap sostitutiva non è considerata una forma di trattam sistemico ed è consentita
11.Presenta diagnosi di immunodef o trattam cronico con steroidi sistemici (in dosi superiori a 10 mg/die di un equivalente del prednisone) o qualsiasi altra forma di terap immunosop nei 7gg prec la 1°dose del trattam sperim
12.Ha un’anamnesi di polmonite (non infettiva) che ha richiesto l’uso di steroidi o presenta una polmonite in atto
13.Ha un’anamnesi nota positiva per malattia polmonare interstiziale La diffusione linfangitica dell’NSCLC non costituisce un criterio di esclusione
14.Presenta infezione attiva con necessità di terap sistemica
15.Ha un’anamnesi nota positiva per infezione da HIV
16.Ha un’anamnesi nota di epatite B (HBsAg reattivo) o epatite C nota in atto (determinazione [qualitativa] dell’RNA del virus dell’epatite C [HCV RNA])
17.Ha un’anamnesi oppure evidenze attuali di qualsiasi condiz, terap o anomalia di lab che possa confondere i risultati dello studio,interferire con la partecip del sog allo studio per la sua intera durata o casi in cui non è nel migliore interesse del sog partecipare,secondo il giudizio dello sperimentatore
18.Presenta disturbi noti di natura psichiatrica o correlati all’abuso di sostanze che potrebbero interferire con il rispetto dei requisiti dello studio
19.Se il partecip si è sottoposto a un intervento di chirurgia maggiore deve essersi ripreso adeguatamente dalla procedura e/o dalle complicanze correlate all’intervento prima di iniziare il trattam sperim
20.Ha avuto un trapianto allogenico di organo solido/tessuto |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| 1. Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) Assessment |
| 1. Sopravvivenza libera da progressione (PFS) valutata mediante revisione centrale indipendente in cieco (BICR) secondo i criteri di valutazione della risposta nei tumori solidi 1.1 (RECIST 1.1) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 1. Up to approximately 27 months |
| 1. Fino a circa 27 mesi |
|
| E.5.2 | Secondary end point(s) |
1. Objective Response (OR) per RECIST 1.1 by BICR Assessment
2. Overall Survival (OS)
3. Duration of Response (DOR) per RECIST 1.1 by BICR Assessment
4. Number of Participants Who Experienced an Adverse Event (AE)
5. Number of Participants Who Discontinued Study Treatment Due to an AE
|
1. Risposta Obiettiva (OR) secondo RECIST 1.1 valutato mediante BICR
2. Sopravvivenza globale (OS)
3. durata della risposta (DOR) secondo RECIST 1.1 valutato mediante BICR
4. Numero di partecipanti che hanno subito un evento avverso (EA)
5. Numero di partecipanti che hanno interrotto il trattamento di studio a causa di un evento avverso (EA) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 27 months
2. Up to approximately 77 months
3. Up to approximately 77 months
4. Up to approximately 77 months
5. Up to approximately 37 months |
1. Fino a circa 27 mesi
2. Fino a circa 77 mesi
3. Fino a circa 77 mesi
4. Fino a circa 77 mesi
5. Fino a circa 37 mesi |
|
| 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 | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Braccio 1,3 Doppio cieco, braccio 2 in aperto |
| Arms 1,3 double-blind; arm 2 open |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 47 |
| 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 |
| Brazil |
| Chile |
| Israel |
| Korea, Republic of |
| Malaysia |
| Russian Federation |
| Taiwan |
| Thailand |
| United States |
| Austria |
| Belgium |
| Denmark |
| Finland |
| France |
| Germany |
| Italy |
| Poland |
| Spain |
| Argentina |
|
| 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
|
|
| 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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