Study of Efficacy and Safety of JDQ443 Single-agent as First-line Treatment for Patients With Locally Advanced or Metastatic KRAS G12C- Mutated Non-small Cell Lung Cancer With a PD-L1 Expression < 1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation.
Novartis Investigative Site 13125 Berlin (Berlin) GermanyRekrutierend» Google-MapsNovartis Investigative Site 06120 Halle (Saale) (Sachsen-Anhalt) GermanyRekrutierend» Google-MapsNovartis Investigative Site 31787 Harburg (Hamburg) GermanyRekrutierend» Google-Maps
Novartis Investigative Site 58675 Hemer (Nordrhein-Westfalen) GermanyRekrutierend» Google-MapsNovartis Investigative Site 87439 Kempten (Bayern) GermanyRekrutierend» Google-MapsNovartis Investigative Site 26121 Oldenburg (Niedersachsen) GermanyRekrutierend» Google-MapsNovartis Investigative Site 72076 Tuebingen (Baden-Württemberg) GermanyRekrutierend» Google-MapsHartford Hospital 06102 Hartford United StatesRekrutierend» Google-Maps Ansprechpartner: Joshua Lopez Phone: 860-545-5000 E-Mail: Joshua.lopez@hhchealth.org» Ansprechpartner anzeigenUniversity of Toledo Precision Oncology 43606 Toledo United StatesRekrutierend» Google-Maps Ansprechpartner: Katherine Behrens E-Mail: Katherine.Behrens@utoledo.edu» Ansprechpartner anzeigenThe Brown University Oncology Group 02903 Providence United StatesRekrutierend» Google-Maps Ansprechpartner: Robert Jarbadan Phone: 401-444-5435 E-Mail: rjarbadan@lifespan.org» Ansprechpartner anzeigenNovartis Investigative Site B1629AHJ Pilar 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1. Overall response rate (ORR) by blinded independent review committee (BIRC) in cohort A (Time Frame - Up to approximately 24 months): ORR is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per response evaluation criteria in solid tumors (RECIST) version 1.1 by BIRC in cohort A
Secondary outcome:
1. ORR by BIRC in cohort B (Time Frame - Up to approximately 24 months): ORR is defined as the percentage of participants with a CR or PR as BOR per RECIST 1.1 by BIRC in cohort B
2. Duration of response (DOR) by BIRC in both cohorts (Time Frame - From first documented response to disease progression or death, up to approximately 24 months): DOR is defined as the time from the first occurrence of a PR or a CR per RECIST 1.1 by BIRC to the occurrence of disease progression or death due to any cause. DOR will be calculated separately for each of the two cohorts.
3. Progression Free Survival (PFS) by BIRC in both cohorts (Time Frame - From first study treatment to first documented progression or death, up to approximately 24 months): PFS is defined as the time from the date of first dose of study treatment to the date of the first documented disease progression per RECIST 1.1 by BIRC or date of death due to any cause. PFS will be calculated separately for each of the two cohorts.
4. Overall survival (OS) in both cohorts (Time Frame - From enrollment to death, up to approximately 36 months): OS is defined as the time from the date of enrollment to the date of death due to any cause. OS will be calculated separately for each of the two cohorts.
5. Disease control rate (DCR) by BIRC in both cohorts (Time Frame - Up to approximately 24 months): DCR is defined as the percentage of participants with a BOR of confirmed CR, PR and stable disease (SD) per RECIST 1.1 by BIRC. DCR will be calculated separately for each of the two cohorts.
6. Time to response (TTR) by BIRC in both cohorts (Time Frame - From enrollment to first documented response, up to approximately 24 months): TTR is defined as the time from the date of enrollment to the date of first documented response of either CR or PR per RECIST 1.1 by BIRC. TTR will be calculated separately for each of the two cohorts.
7. ORR by local radiology assessment in both cohorts (Time Frame - Up to approximately 24 months): ORR is defined as the percentage of participants with a CR or PR as BOR per RECIST 1.1 by local review assessment. ORR will be calculated separately for each of the two cohorts.
8. DOR by local review assessment in both cohorts (Time Frame - From first documented response to disease progression or death, up to approximately 24 months): DOR is defined as the time from the first occurrence of a PR or a CR per RECIST 1.1 by local review assessment to the occurrence of disease progression or death due to any cause. DOR will be calculated separately for each of the two cohorts.
9. DCR by local review assessment in both cohorts (Time Frame - Up to approximately 24 months): DCR is defined as the percentage of participants with a BOR of confirmed CR, PR and SD per RECIST 1.1 by local review assessment. DCR will be calculated separately for each of the two cohorts.
10. TTR by local review assessment in both cohorts (Time Frame - From enrollment to first documented response, up to approximately 24 months): TTR is defined as the time from the date of enrollment to the date of first documented response of either CR or PR per RECIST 1.1 by local review assessment. TTR will be calculated separately for each of the two cohorts.
11. PFS by local review assessment in both cohorts (Time Frame - From first study treatment to first documented progression or death, up to approximately 24 months): PFS is defined as the time from the date of first dose of study treatment to the date of the first documented disease progression per RECIST 1.1 by local review assessment or date of death due to any cause. PFS will be calculated separately for each of the two cohorts.
12. ORR by BIRC and local radiology assessment for participants whose tumors harbor an STK11 mutation regardless of PD-L1 expression status (pooled from both cohorts) (Time Frame - Up to approximately 24 months): ORR is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per RECIST 1.1 by local review assessment and by BIRC. ORR will be calculated for all participants whose tumors harbor an STK11 mutation by pooling participants from both cohorts
13. DOR by BIRC and local radiology assessment for participants whose tumors harbor an STK11 mutation regardless of PD-L1 expression status (pooled from both cohorts) (Time Frame - From first documented response to disease progression or death, up to approximately 24 months): DOR is defined as the time from the first occurrence of a PR or a CR per RECIST 1.1 by local review assessment and by BIRC to the occurrence of disease progression or death due to any cause. DOR will be calculated for all participants whose tumors harbor an STK11 mutation by pooling participants from both cohorts.
14. DCR by BIRC and local radiology assessment for participants whose tumors harbor an STK11 mutation regardless of PD-L1 expression status (pooled from both cohorts) (Time Frame - Up to approximately 24 months): DCR is defined as the percentage of participants with a BOR of confirmed CR, PR and stable disease (SD) per RECIST 1.1 by local review assessment and by BIRC. DCR will be calculated for all participants whose tumors harbor an STK11 mutation by pooling participants from both cohorts
15. TTR by BIRC and local radiology assessment for participants whose tumors harbor an STK11 mutation regardless of PD-L1 expression status (pooled from both cohorts) (Time Frame - From enrollment to first documented response, up to approximately 24 months): TTR is defined as the time from the date of enrollment to the date of first documented response of either CR or PR per RECIST 1.1 by local review assessment and by BIRC. TTR will be calculated for all participants whose tumors harbor an STK11 mutation by pooling participants from both cohorts
16. PFS by BIRC and local radiology assessment for participants whose tumors harbor an STK11 mutation regardless of PD-L1 expression status (pooled from both cohorts) (Time Frame - From first study treatment to first documented progression or death, up to 24 months): PFS is defined as the time from the date of first dose of study treatment to the date of the first documented disease progression per RECIST 1.1 by local review assessment and BIRC or date of death due to any cause. PFS will be calculated for all participants whose tumors harbor an STK11 mutation by pooling participants from both cohorts
17. OS for participants whose tumors harbor an STK11 mutation regardless of PD-L1 expression status (pooled from both cohorts) (Time Frame - From enrollment to death, up to approximately 36 months): OS is defined as the time from the date of enrollment to the date of death due to any cause. OS will be calculated for all participants whose tumors harbor an STK11 mutation by pooling participants from both cohorts
18. Maximum concentration (Cmax) of JDQ443 in plasma (Time Frame - Up to approximately 24 months): Blood samples will be collected for pharmacokinetics characterization.
19. Time to reach maximum concentration at steady-state (Tmax,ss) of JDQ443 in plasma (Time Frame - Up to approximately 24 months): Blood samples will be collected for pharmacokinetics characterization.
20. Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of JDQ443 in plasma (Time Frame - Up to approximately 24 months): Blood samples will be collected for pharmacokinetics characterization.
21. Area Under the Curve From Time Zero to the last measurable concentration sampling time at steady-state (AUClastss) of JDQ443 in plasma (Time Frame - Up to approximately 24 months): Blood samples will be collected for pharmacokinetics characterization.
22. Observed concentration at the end of a dosing interval at steady-state (Cmin,ss) of JDQ443 in plasma (Time Frame - Up to approximately 24 months): Blood samples will be collected for pharmacokinetics characterization.
23. Total body clearance (CL/F) of JDQ443 from the plasma (Time Frame - Up to approximately 24 months): Blood samples will be collected for pharmacokinetics characterization.
24. Time to definitive deterioration (TTDD) in NSCLC-SAQ total score (Time Frame - From baseline up to approximately 24 months): The Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) is a 7-item, patient-reported outcome measure which assess patient-reported symptoms associated with advanced NSCLC: cough, pain, dyspnea, fatigue, and appetite.
25. TTDD in the physical functioning scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30 (Time Frame - From baseline up to approximately 24 months): The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/QoL scale, and six single items (constipation, diarrhea, insomnia, shortness of breath, appetite loss and financial difficulties).
26. Chain from baseline in NSCLC-SAQ (Time Frame - From baseline up to approximately 24 months): The NSCLC-SAQ is a 7-item, patient-reported outcome measure which assess patient-reported symptoms associated with advanced NSCLC: cough, pain, dyspnea, fatigue, and appetite.
27. Change from baseline in EORTC QLQ-C30 (Time Frame - From baseline up to approximately 24 months): The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/QoL scale, and six single items (constipation, diarrhea, insomnia, shortness of breath, appetite loss and financial difficulties).
Experimental: Cohort A- PD-L1<1% Participants whose tumors harbor a KRAS G12C mutation and a PD-L1 expression <1%, regardless of STK11 mutation status.
Experimental: Cohort B- PD-L1≥ 1% and STK11 mutation Participants whose tumors harbor a KRAS G12C mutation, a PD-L1 expression ≥ 1% and an STK11 co-mutation.
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"Study of Efficacy and Safety of JDQ443 Single-agent as First-line Treatment for Patients With Locally Advanced or Metastatic KRAS G12C- Mutated Non-small Cell Lung Cancer With a PD-L1 Expression < 1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation."
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