| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic Non Small Cell Lung Cancer (NSCLC) |
| Metastazirani karcinom nemalih stanica pluća |
|
| E.1.1.1 | Medical condition in easily understood language |
| Lung cancer that has spread to other parts of the body |
| Karcinom pluća koji se proširio na druge dijelove tijela |
|
| 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 |
| • To demonstrate superiority of the combination of JTX-4014 with vopratelimab over JTX-4014 monotherapy in biomarker-selected subjects |
| • Dokazati superiornost lijeka JTX-4014 u kombinaciji s vopratelimabom u odnosu na samostalnu primjenu lijeka JTX-4014 u ispitanika izabranih prema biološkim biljezima. |
|
| E.2.2 | Secondary objectives of the trial |
•To evaluate efficacy as measured by ORR, PFS, landmark PFS at 9 months, disease control rate, duration of response, and OS
• To evaluate the safety and tolerability of JTX-4014 alone and in combination with vopratelimab
• To evaluate the PK of JTX-4014 and vopratelimab
• To assess the immunogenicity of JTX-4014 and vopratelimab
• To evaluate association of baseline tumor RNA signature score with clinical outcomes |
• Procijeniti učinkovitost mjerenu ukupnom stopom odgovora, preživljenjem bez progresije bolesti, preživljenjem bez progresije bolesti u specificiranoj vremenskoj točki nakon 9 mjeseci, stopom kontrole bolesti, trajanjem odgovora i ukupnim preživljenjem.
• Procijeniti sigurnost i podnošljivost lijeka JTX-4014 u samostalnoj primjeni i u kombinaciji s vopratelimabom.
• Procijeniti farmakokinetiku lijeka JTX-4014 i vopratelimaba.
• Procijeniti imunogenost lijeka JTX-4014 i vopratelimaba.
• Procijeniti povezanost početnog potpisa tumorskog RNK s kliničkim ishodima.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Able and willing to participate and comply with all study requirements and provide signed and dated informed consent prior to initiation of any study procedures
2. Histologically or cytologically confirmed diagnosis of NSCLC with evaluable or measurable disease according to RECIST v1.1 with at least 1 measurable lesion
3. Confirmed tumor RNA signature score ≥ 7.9
4. Experienced progression of locally advanced or metastatic NSCLC after 1 prior systemic antineoplastic platinum-containing regimen (adjuvant therapy will count as a regimen if administered within 1 year before the relapse)
5. Age of ≥ 18 years
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Predicted life expectancy of ≥ 3 months
8. The following laboratory values:
a. Hemoglobin ≥ 9.0 g/dL
b. Platelet count ≥ 75 × 109 cells/L
c. Absolute neutrophil count > 1.5 × 109 and < 10 × 109 cells/L
d. Serum creatinine < 2 × the upper limit of normal (ULN)
e. Total bilirubin ≤ ULN, unless the subject has a known diagnosis of Gilbert’s syndrome
f. Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × ULN
g. Serum albumin ≥ 75% of the lower limit of normal
h. Lactate dehydrogenase ≤ 550 U/L
9. If with medical history of the following, eligibility should be discussed with the Medical Monitor:
a. Prior biliary tract disorders (based on Medical Dictionary for Regulatory Activities [MedDRA] system organ class of Hepatobiliary disorders and MedDRA high-level terms of Obstructive bile duct disorders, Hepatic vascular disorders, and Structural and other bile duct disorders)
b. Portal hypertension and/or hepatic vascular disorders
10. For women of childbearing potential (WOCBP): negative serum pregnancy test within 72 hours prior to planned C1D1 and a negative urine or serum pregnancy test on C1D1. In addition, the WOCBP must be willing to complete a urine or serum pregnancy test prior to each dose of either study drug.
11. WOCBP and males whose partners are WOCBP must agree to use a highly effective method of birth control throughout their participation and for 5 months following the last study drug administration. Highly effective methods of birth control are defined as those that, alone or in combination, result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. |
1. Sposobnost i volja za sudjelovanje i usklađivanje sa svim zahtjevima iz ispitivanja te davanje potpisanog i datiranog informiranog pristanka prije početka bilo kojeg postupka iz ispitivanja.
2. Histološki ili citološki potvrđena dijagnoza karcinoma pluća nemalih stanica s procjenjivom ili mjerljivom bolešću u skladu s kriterijima RECIST inačice 1.1) uz najmanje 1 mjerljivu leziju
3. Potvrđeni potpis tumorskog RNK ≥7,9.
4. Postojanje progresije lokalno uznapredovalog ili metastatskog karcinoma pluća nemalih stanica nakon 1 prethodne sistemske antineoplastične terapije koja je sadržavala platinu (adjuvantna terapija prihvatit će se ako se davala unutar 1 godine prije relapsa).
5. Starost ≥ 18 godina.
6. Opće stanje zdravlja 0 ili 1 prema ljestvici Istočne kooperativne onkološke skupine (engl. Eastern Cooperative Oncology Group [ECOG]).
7. Predviđeno trajanje života ≥ 3 mjeseca.
8. Sljedeće laboratorijske vrijednosti:
a. hemoglobin ≥ 9,0 g/dl
b. broj trombocita ≥ 75 × 109 stanica/l
c. apsolutni broj neutrofila > 1,5 × 109 i < 10 × 109 stanica/l
d. kreatinin u serumu < 2 × gornja granica referentnih vrijednosti
e. ukupni bilirubin ≤ od gornje granice referentnih vrijednosti osim ako ispitanik ima poznatu dijagnozu Gilbertova sindroma
f. aspartat aminotransferaza i alanin aminotransferaza ≤ 2,5 × gornja granica referentnih vrijednosti
g. albumin u serumu ≥ 75% od donje granice referentnih vrijednosti
h. laktat dehidrogenaza ≤ 550 jedinica/l.
9. Podobnost je potrebno razmotriti s medicinskim motriteljem ako postoji povijest sljedećeg:
a. prethodni poremećaji bilijarnog sustava (na temelju klase organskog sustava iz Medicinskog rječnika za regulatorne aktivnosti [engl. Medical Dictionary for Regulatory Activities {MedDRA}] za hepatobilijarne poremećaje i izraza visoke razine iz rječnika MedDRA za opstruktivne poremećaje žučovoda, poremećaje krvožilnog sustava jetre te strukturalne i druge poremećaje žučovoda)
b. portalna hipertenzija i/ili poremećaji krvožilnog sustava jetre.
10. Za ispitanice koje mogu zatrudnjeti: negativni test na trudnoću na serumu unutar 72 sata prije planiranog 1. dana 1. ciklusa i negativni test na trudnoću na mokraći ili serumu 1. dan 1. ciklusa. Žene koje mogu zatrudnjeti dodatno trebaju pristati na test na trudnoću na mokraći ili serumu prije primanja svake doze bilo kojeg ispitivanog lijeka.
11. Ispitanice koje mogu zatrudnjeti i ispitanici čije partnerice mogu zatrudnjeti moraju pristati na korištenje visokoučinkovite metode kontracepcije tijekom sudjelovanja u ispitivanju i 5 mjeseci nakon primanja zadnje doze ispitivanog lijeka. Visoko učinkovite metode kontracepcije definirane su kao one koje samostalno ili u kombinaciji s drugima rezultiraju niskom stopom neuspjeha (odnosno, manje od 1% na godinu) kad se stalno i ispravno koriste.
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| E.4 | Principal exclusion criteria |
1. Concurrent anticancer treatment or subject is expected to require any other form of antineoplastic therapy while on study, either approved or investigational
2. Current or past participation in a study of an investigational agent or using an investigational device in the metastatic setting
3. Chemotherapy < 28 days prior to planned C1D1
4. Prior immunotherapy including, but not limited to PD-1 or PD-L1 inhibitor mAb at any time, including JTX-4014; therapy with any mAb that specifically binds to ICOS, including vopratelimab; or chimeric antigen receptor T cell therapy
5. Use of anticancer therapies listed below in the metastatic setting (allowed as prior treatment for localized disease):
a. Biologic therapy
b. Targeted small molecule therapy
c. Organ transplantation, including allogeneic or autologous stem cell transplantation
6. Positive test for any of the following EGFR gene mutations in blood or tumor: Exon 18 G719A; Exon 18 G719C; Exon 18 G719S; Exon 19 Del; Exon 20 S768I; Exon 20 T790M; Exon 20 Ins; Exon 21 L858R; Exon 21 L861Q
7. The following toxicity history:
a. Ongoing toxicity attributed to prior therapy that was Grade > 1 according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
Exceptions: Grade > 1 toxicities that, in the opinion of the Investigator, should not exclude the subject (e.g., alopecia, Grade 2 neuropathy, hypo- or hyperthyroidism, or other endocrinopathies that are well controlled with hormone replacement therapy) and are approved by the Medical Monitor
b. History of pneumonitis or interstitial lung disease
c. Symptomatic ascites or pleural effusion (subjects who are clinically stable for > 3 months following treatment for these conditions [including therapeutic thoraco- or paracentesis] are eligible)
d. If with medical history of the following, eligibility should be discussed with the Medical Monitor: colitis, hepatitis, nephritis, skin reactions, or encephalitis.
8. Known severe intolerance or life-threatening hypersensitivity reactions to humanized mAbs or IV Ig preparations; any history of anaphylaxis; prior history of human anti-human antibody response; or known allergy to any of the study drugs (including their analogues or excipients [L-histidine, mannitol, sodium chloride, or polysorbate 80])
9. Major surgery (excluding minor procedures, e.g., placement of vascular access, gastrointestinal/biliary stent, and biopsy) < 4 weeks prior to planned C1D1
10. Prior whole brain radiation
11. Subjects with the following should be reviewed with the Medical Monitor prior to enrollment:
a. Brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation
b. Radiation (other than whole brain radiation) has been or will be administered < 21 days prior to planned C1D1
12. Active and clinically relevant bacterial, fungal, or viral infection, including known hepatitis B, C, or human immunodeficiency virus (testing not required)
13. Receipt of live vaccines within 30 days of planned C1D1 (Inactivated vaccines are allowed; seasonal vaccines should be up-to-date prior to planned C1D1.)
14. Women who are pregnant, breastfeeding, or who plan to become pregnant/breastfeed while on study; men who plan to father children during the study
15. Concurrent second malignancy
16. An active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents at a dose of ≥ 10 mg/day of prednisone equivalent. Subjects who require intermittent use of bronchodilators or local steroid injections will not be excluded from the study. Subjects with hypothyroidism who are stable on hormone replacement therapy will not be excluded from the study.
17. Medical or social condition that, in the opinion of the Investigator, might place the subject at an increased risk, adversely affect compliance, or confound safety or other clinical study data interpretation
18. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study |
1. Popratna antikarcinomska terapija ili očekivana potreba za bilo kojim drugim oblikom antineoplastične terapije tijekom ispitivanja, bilo odobrenim, bilo ispitivanim lijekom.
2. Tekuće ili prošlo sudjelovanje u ispitivanju ispitivanog lijeka ili korištenje ispitivanog sredstva u liječenju metastaza.
3. Kemoterapija < 28 dana prije planiranog 1. dana 1. ciklusa.
4. Prethodna imunoterapija, uključujući, ali se ne ograničavajući samo na primjenu monoklonskih protutijela inhibitora PD-1 ili PD‑L1 u bilo kojem trenutku, uključujući JTX-4014; terapija bilo kojim monoklonskim protutijelima koji se specifično vezuju na ICOS, uključujući vopratelimab ili terapija himernim antigenskim receptorima T-stanica.
5. Korištenje dolje navedenih antikarcinomskih terapija u slučaju postojanja metastaza (dopušteno kao prethodno liječenje lokalizirane bolesti):
a. terapija biološkim lijekovima
b. terapija ciljana na male molekule
c. presađivanje organa, uključujući presađivanje alogenih ili autolognih matičnih stanica.
6. Pozitivan rezultat testa na bilo koju od sljedećih mutacija gena receptora epidermalnog faktora rasta (engl. epidermal growth factor receptor [EGFR]) u krvi ili tumoru: ekson 18 G719A, ekson 18 G719C, ekson 18 G719S, ekson 19 Del, ekson 20 S768I, ekson 20 T790M, ekson 20 Ins, ekson 21 L858R i ekson 21 L861Q.
7. Povijest sljedećih toksičnosti:
a. trenutna toksičnost pripisana prethodnoj terapiji stupnja > 1 prema Općim terminološkim kriterijima za štetne događaje Nacionalnog instituta za karcinome (engl. National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE])
Iznimke: toksičnosti stupnja > 1 koje, prema mišljenju ispitivača, ne bi trebale isključivati ispitanika (na primjer, alopecija; neuropatija, hipo- ili hipertireoza ili druga endokrinopatija stupnja 2 koja je dobro kontrolirana nadomjesnom hormonskom terapijom) i koje odobri medicinski motritelj
b. povijest pneumonitisa ili intersticijske bolesti pluća
c. simptomatski ascites ili pleuralni izljev (ispitanici koji su klinički stabilni tijekom > 3 mjeseca nakon liječenja tih stanja [uključujući terapijsku torako- ili paracentezu] podobni su za sudjelovanje u ispitivanju)
d. podobnost za ispitivanje treba se razmotriti s medicinskim motriteljem u slučaju kolitisa, hepatitisa, nefritisa, kožnih reakcija ili encefalitisa.
8. Poznata jaka netolerancija ili reakcije preosjetljivosti opasne po život na preparate humaniziranih monoklonskih protutijela ili imunoglobulina za intravensku primjenu, bilo kakva povijest anafilakse, povijest odgovora na humana antihumana protutijela ili poznata alergija na bilo koji od ispitivanih lijekova (uključujući njihove analoge ili pomoćne tvari [L histidin, manitol, kuhinjska sol ili polisorbat 80]).
9. Značajniji kirurški zahvat (isključujući manje zahvate poput omogućavanja vaskularnog pristupa, gastrointestinalni ili bilijarni stent i biopsija) < 4 tjedna prije planiranog 1. dana 1. ciklusa.
10. Prethodno zračenje cijelog mozga.
11. Prije uključivanja medicinski motritelj treba pregledati ispitanike sa sljedećim:
a. metastaze na mozgu, leptomeningealne metastaze ili kompresija kralježničke moždine koja nije potpuno izliječena operacijom ili zračenjem
b. zračenje (osim zračenja cijelog mozga) se primjenjivalo ili će se primjenjivati < 21 dan prije planiranog 1. dana 1. ciklusa.
12. Aktivna i klinički značajna bakterijska, gljivična ili virusna infekcija, uključujući poznati hepatitis B ili C ili virus ljudske imunodeficijencije (testiranje nije potrebno).
13. Primanje živih cjepiva unutar 30 dana od planiranog 1. dana 1. ciklusa (inaktivirana cjepiva su dopuštena, sezonska cjepiva trebaju biti obnovljena prije planiranog 1. dana 1. ciklusa).
14. Trudnice i dojilje ili ispitanice koje planiraju zatrudnjeti ili dojiti tijekom ispitivanja i ispitanici koji tijekom ispitivanja planiraju začeti dijete.
15. Popratna druga zloćudna bolest.
16. Aktivna autoimuna bolest ili dokumentirana povijest autoimune bolesti ili sindroma koji zahtijevaju sistemsku primjenu steroida ili imunosupresiva u dozi ≥ 10 mg/dan ekvivalenta prednizona. Ispitanici kojima je potrebno povremeno korištenje bronhodilatatora ili lokalne injekcije steroida mogu se uključiti u ispitivanje. Ispitanici s hipotireozom koji primaju stabilnu nadomjesnu hormonsku terapiju mogu sudjelovati u ispitivanju.
17. Medicinsko ili socijalno stanje koje bi prema mišljenju ispitivača moglo povećati rizik za ispitanika ili negativno utjecati na usklađivanje sa zahtjevima ispitivanja i tumačenje sigurnosnih ili drugih podataka iz kliničkog ispitivanja.
18. Poznati psihijatrijski poremećaj ili zloporaba droga ili alkohola koji bi mogli utjecati na usklađivanje sa zahtjevima ispitivanja.
|
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Mean percent change from baseline tumor size of all measurable existing and new lesions averaged over 9 and 18 weeks |
| • Prosječna postotna promjena svih mjerljivih postojećih i novih lezija uprosječena tijekom 9 i 18 tjedana u odnosu na početnu veličinu tumora. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Study assessments and procedures will be performed as outlined in the Protocol Appendix 1 (Schedule of Assessments and Sampling Time Points for Cohort MC1) and Appendix 2 (Schedule of
Assessments and Sampling Time Points for Cohorts CC1 and CC2). |
| Postupci u ispitivanju biti će napravljeni u skladu sa Dodatkom Plana br. 1 (za kohortu MC1) te Dodatkom br. 2 (za kohorte CC1 i CC2) |
|
| E.5.2 | Secondary end point(s) |
• ORR (percentage of subjects with CR + PR) according to RECIST, v1.1
• PFS according to RECIST, v1.1
• Landmark PFS rate at 9 months according to RECIST, v1.1
• Disease control rate (confirmed CR + confirmed PR + unconfirmed SD) according to RECIST, v1.1
• Duration of response in months according to RECIST, v1.1
• OS
• Incidence and grade of treatment-emergent adverse events (TEAEs)
• PK properties of JTX-4014 and vopratelimab
• Incidence of ADAs to either JTX-4014 or vopratelimab
• Incidence of neutralizing antibody (NAb) to either JTX-4014 or vopratelimab
• Association of baseline tumor RNA signature score with clinical outcomes |
• Ukupna stopa odgovora (postotak ispitanika s potpunim i djelomičnim odgovorom u skladu s Kriterijima za procjenu odgovora solidnih tumora inačice 1.1 (engl. Response Evaluation Criteria in Solid Tumors [RECIST] v1.1).
• Preživljenje bez progresije bolesti u skladu s kriterijima RECIST inačice 1.1.
• Stopa preživljenja bez progresije bolesti u specificiranoj vremenskoj točki nakon 9 mjeseci u skladu s kriterijima RECIST inačice 1.1.
• Stopa kontrole bolesti (potvrđeni potpuni odgovor + potvrđeni djelomični odgovor + nepotvrđena stabilizacija bolesti) u skladu s kriterijima RECIST inačice 1.1.
• Trajanje odgovora u mjesecima u skladu s kriterijima RECIST inačice 1.1.
• Ukupno preživljenje.
• Učestalost i težina štetnih događaja proizašlih iz liječenja.
• Farmakokinetička svojstva lijeka JTX-4014 i vopratelimaba.
• Učestalost protutijela protiv lijeka, bilo protiv lijeka JTX-4014 ili vopratelimaba.
• Učestalost neutralizirajućih protutijela, bilo protiv lijeka JTX-4014 ili vopratelimaba.
• Povezanost početnog potpisa tumorskog RNK s kliničkim ishodima.
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|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Study assessments and procedures will be performed as outlined in the Protocol Appendix 1 (Schedule of Assessments and Sampling Time Points for Cohort MC1) and Appendix 2 (Schedule of
Assessments and Sampling Time Points for Cohorts CC1 and CC2). |
| Postupci u ispitivanju biti će napravljeni u skladu sa Dodatkom Plana br. 1 (za kohortu MC1) te Dodatkom br. 2 (za kohorte CC1 i CC2) |
|
| 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 | Yes |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 39 |
| 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 | No |
| 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 |
| Belarus |
| Bosnia and Herzegovina |
| Bulgaria |
| Croatia |
| Czechia |
| Georgia |
| Hungary |
| Latvia |
| Moldova, Republic of |
| Poland |
| Romania |
| Russian Federation |
| Serbia |
| Slovakia |
| Turkey |
| Ukraine |
|
| 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
|
| LVLS |
| Zadnji posjet zadnjeg uključenog ispitanika |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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