Cologne University Hospital Cologne (Nordrhein-Westfalen) GermanyRekrutierend» Google-MapsUCI Medical Center 92868 Orange United StatesRekrutierend» Google-MapsStanford Medicine 94305 Palo Alto United StatesRekrutierend» Google-Maps
UC Davis Comprehensive Cancer Center 95817 Sacramento United StatesRekrutierend» Google-MapsUniversity of Colorado Cancer Center 80045 Denver United StatesRekrutierend» Google-MapsGeorgetown University Medical Center 20007 Washington United StatesRekrutierend» Google-MapsUniversity of Miami 33146 Coral Gables United StatesRekrutierend» Google-MapsMass General Hospital 02114 Boston United StatesRekrutierend» Google-MapsHenry Ford Cancer Institute 48202 Detroit United StatesRekrutierend» Google-MapsWashington University School of Medicine 63110 Saint Louis United StatesRekrutierend» Google-MapsNYU Langone Health 10016 New York United StatesRekrutierend» Google-MapsMemorial Sloan Kettering Cancer Center 10065 New York United StatesRekrutierend» Google-MapsAtrium Health Levine Cancer Institute 28204 Charlotte United StatesRekrutierend» Google-MapsFox Chase Cancer Center 19111 Philadelphia United StatesRekrutierend» Google-MapsSarah Cannon Research Institute 37203 Nashville United StatesRekrutierend» Google-MapsMD Anderson Cancer Center 77030 Houston United StatesAktiv, nicht rekrutierend» Google-MapsNEXT Oncology - Virginia Cancer Specialists 22031 Fairfax United StatesRekrutierend» Google-MapsUniversity of Washington / Fred Hutchinson Cancer Center 98109 Seattle United StatesRekrutierend» Google-MapsChris O'Brien Lifehouse 2050 Camperdown AustraliaRekrutierend» Google-MapsPeter MacCallum Cancer Centre 3000 Melbourne AustraliaRekrutierend» Google-MapsUniversity Hospital Leuven 3000 Leuven BelgiumRekrutierend» Google-MapsCross Cancer Institute T6G 1Z2 Edmonton CanadaRekrutierend» Google-MapsPrincess Margaret Cancer Research M5GG 1L7 Toronto CanadaRekrutierend» Google-MapsCentre Legon Berard 69008 Lyon FranceRekrutierend» Google-MapsCHU de Nantes 44000 Nantes FranceRekrutierend» Google-MapsHospital Center University De Toulouse 31300 Toulouse FranceRekrutierend» Google-MapsInstitute Gustave Roussy 94805 Villejuif FranceRekrutierend» Google-MapsNational Cancer Center 10408 Gyeonggi-do Korea, Republic ofRekrutierend» Google-MapsSeoul National University Hospital 03080 Seoul Korea, Republic ofRekrutierend» Google-MapsYonsei University Health System 03722 Seoul Korea, Republic ofRekrutierend» Google-MapsSamsung Medical Center Seoul Korea, Republic ofRekrutierend» Google-MapsNetherlands Cancer Institute 1066 Amsterdam NetherlandsRekrutierend» Google-MapsUniversity Medical Centre Groningen Groningen NetherlandsRekrutierend» Google-MapsNational University Hospital Singapore 119074 Singapore SingaporeRekrutierend» Google-MapsNational Cancer Centre Singapore 168583 Singapore SingaporeRekrutierend» Google-MapsUOMI Cancer Center - Clinica Tres Torres 08017 Barcelona SpainRekrutierend» Google-MapsVall d'Hebron University Hospital 08035 Barcelona SpainRekrutierend» Google-MapsUniversity Hospital of A Coruña 15006 Coruna SpainRekrutierend» Google-MapsGregorio Marañón Hospital 28007 Madrid SpainRekrutierend» Google-MapsHospital Universitario 12 de Octubre 28041 Madrid SpainRekrutierend» Google-MapsHospital Universitario HM Sanchinarro 28050 Madrid SpainRekrutierend» Google-MapsChung Shan Medical University Hospital 40201 Taichung TaiwanRekrutierend» Google-MapsNational Cheng Kung University Hospital 704017 Tainan TaiwanRekrutierend» Google-MapsNational Taiwan University Hospital 10002 Taipei TaiwanRekrutierend» Google-Maps
1. Maximum Tolerated Dose (MTD) (Phase 1) (Time Frame - Within 28 days of last patient dosed during dose escalation): Highest dose with dose-limiting toxicity (DLT) rate ≤ 25%
2. Recommended Phase 2 Dose (RP2D) (Time Frame - Within 28 days of last patient dosed during dose escalation.): To determine the RP2D
3. Objective Response Rate (ORR) (Phase 2) (Time Frame - 2-3 years after first patient dosed.): To determine ORR as assessed by BICR
Secondary outcome:
1. Number of participants with treatment-emergent adverse events, as assessed by CTCAE, v5.0 (Time Frame - Approximately 3 years.): Incidence and severity of treatment-emergent adverse events (TEAEs)
2. Maximum plasma concentration (Cmax) of NVL-520 (Time Frame - Pre-dose and up to 24 hours post-dose): To determine the maximum plasma concentration (Cmax) of NVL-520
3. Plasma concentration at the end of the dosing interval (Ctau) of NVL-520 (Time Frame - Pre-dose and up to 24 hours post-dose): To determine the plasma concentration at the end of the dosing interval (Ctau) of NVL-520
4. Average plasma concentration (Cavg) of NVL-520 (Time Frame - Pre-dose and up to 24 hours post-dose): To determine the average plasma concentration (Cavg) of NVL-520
5. Time of maximum concentration (Tmax) of NVL-520 (Time Frame - Pre-dose and up to 24 hours post-dose): To determine the time of maximum concentration (Tmax) of NVL-520
6. Area under the curve at the end of the dosing interval (AUCtau) of NVL-520 (Time Frame - Pre-dose and up to 24 hours post-dose): To determine the area under the curve at the end of the dosing interval (AUCtau) of NVL-520
7. Area under the curve from time 0 to 24 (AUC0-24) of NVL-520 (Time Frame - Pre-dose and up to 24 hours post-dose): To determine the area under the curve from time 0 to 24 (AUC0-24) of NVL-520
8. Area under the curve from time 0 to infinity (AUCinf) of NVL-520 (Time Frame - Pre-dose and up to 24 hours post-dose): To determine the area under the curve from time 0 to infinity (AUCinf) of NVL-520
9. Oral clearance (CL/F) of NVL-520 (Time Frame - Pre-dose and up to 24 hours post-dose): To determine the oral clearance (CL/F) of NVL-520
10. Volume of distribution (Vz/F) of NVL-520 (Time Frame - Pre-dose and up to 24 hours post-dose): To determine the volume of distribution (Vz/F) of NVL-520
11. Half-life (t1/2) of NVL-520 (Time Frame - Pre-dose and up to 24 hours post-dose): To determine the half-life (t1/2) of NVL-520
12. Objective response rate (ORR) (Time Frame - 2-3 years after first patient dosed): Determine ORR as assessed by BICR
13. Duration of response (DOR) (Time Frame - 2-3 years after first patient dosed): Determine DOR of NVL-520 until radiographic disease progression or death
14. Clinical benefit rate (CBR) (Time Frame - 2-3 years after first patient dosed): Determine CBR of NVL-520
15. Time to response (Time Frame - 2-3 years after first patient dosed): Determine time to response of NVL-520
16. Progression-free survival (PFS) (Time Frame - Approximately 3 years): Determine PFS of NVL-520 until radiographic disease progression or death
17. Overall survival (OS) (Time Frame - Approximately 3 years): Determine OS
18. Rate of CNS progression (Time Frame - Approximately 3 years): The incidence of CNS as first site of progression, alone or with concurrent extra-CNS progression
19. Intracranial objective response rate (IC-ORR) (Time Frame - Approximately 3 years): Determine the intracranial objective response rate
20. Quality of life assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) (Time Frame - 2-3 years after first patient dosed): EORTC QLQ-C30 measures cancer patients' physical, psychological, and social functions. Scale ranges from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much." Higher score for the functioning scales and global health status denotes a better level of functioning, while higher scores on the symptom and single-item scales indicate a higher level of symptoms.
21. Quality of life assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 module (EORTC QLQ-LC29) (Time Frame - 2-3 years after first patient dosed): EORTC-QLQ-LC29 measures the quality of life in patients with lung cancer. Symptom scale ranges from: 1, "Not at all"; 2, "A little"; 3, "Quite a bit"; to 4, "Very much." For symptoms scales, higher scores indicated greater symptom burden.