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JOURNAL ONKOLOGIE – STUDIE

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.

Rekrutierend

NCT-Nummer:
NCT05445843

Studienbeginn:
Dezember 2022

Letztes Update:
28.02.2024

Wirkstoff:
JDQ443

Indikation (Clinical Trials):
Lung Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Novartis Pharmaceuticals

Collaborator:
-

Kontakt

Studienlocations
(3 von 79)

Novartis Investigative Site
13125 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
06120 Halle (Saale)
(Sachsen-Anhalt)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
31787 Harburg
(Hamburg)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
58675 Hemer
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
87439 Kempten
(Bayern)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
26121 Oldenburg
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
72076 Tuebingen
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
B1629AHJ Pilar
ArgentinaRekrutierend» Google-Maps
Novartis Investigative Site
C1431FWO Buenos Aires
ArgentinaRekrutierend» Google-Maps
Novartis Investigative Site
S2000DSV Rosario
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Novartis Investigative Site
C1426AGE Buenos Aires
ArgentinaRekrutierend» Google-Maps
Novartis Investigative Site
X5000JHQ Cordoba
ArgentinaRekrutierend» Google-Maps
Novartis Investigative Site
X5016KEH Cordoba
ArgentinaRekrutierend» Google-Maps
Novartis Investigative Site
A 6807 Feldkirch
AustriaRekrutierend» Google-Maps
Novartis Investigative Site
9020 Klagenfurt
AustriaRekrutierend» Google-Maps
Novartis Investigative Site
9100 Sint Niklaas
BelgiumRekrutierend» Google-Maps
Novartis Investigative Site
8800 Roeselare
BelgiumRekrutierend» Google-Maps
Novartis Investigative Site
41825-010 Salvador
BrazilRekrutierend» Google-Maps
Novartis Investigative Site
30360 680 Belo Horizonte
BrazilRekrutierend» Google-Maps
Novartis Investigative Site
22271-110 Rio de Janeiro
BrazilRekrutierend» Google-Maps
Novartis Investigative Site
90035-001 Rio Grande Do Sul
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Novartis Investigative Site
4109 Branipole
BulgariaRekrutierend» Google-Maps
Novartis Investigative Site
510120 Guang Zhou
ChinaZurückgezogen» Google-Maps
Novartis Investigative Site
450008 Zhengzhou
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Novartis Investigative Site
13915 Marseille cedex 20
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Novartis Investigative Site
34070 Montpellier
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Novartis Investigative Site
44805 Saint Herblain
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Novartis Investigative Site
67091 Strasbourg Cedex
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Novartis Investigative Site
2045 Torokbalint
HungaryRekrutierend» Google-Maps
Novartis Investigative Site
3200 Matrahaza
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Novartis Investigative Site
605006 Puducherry
IndiaRekrutierend» Google-Maps
Novartis Investigative Site
05460 Alor Setar
MalaysiaRekrutierend» Google-Maps
Novartis Investigative Site
25200 Kuantan
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Novartis Investigative Site
93586 Kuching
MalaysiaRekrutierend» Google-Maps
Novartis Investigative Site
10990 Pulau Pinang
MalaysiaRekrutierend» Google-Maps
Novartis Investigative Site
4818 CK Breda
NetherlandsRekrutierend» Google-Maps
Novartis Investigative Site
8934 AD Leeuwarden
NetherlandsRekrutierend» Google-Maps
Novartis Investigative Site
1998-018 Lisboa
PortugalRekrutierend» Google-Maps
Novartis Investigative Site
4100-180 Porto
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Novartis Investigative Site
168583 Singapore
SingaporeRekrutierend» Google-Maps
Novartis Investigative Site
90110 Songkhla
ThailandRekrutierend» Google-Maps
Novartis Investigative Site
10400 Bangkok
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Novartis Investigative Site
10700 Bangkok
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Novartis Investigative Site
21000 Diyarbakir
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Novartis Investigative Site
TQ2 7AA Torquay
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Alle anzeigen

Studien-Informationen

Detailed Description:

This is a non-randomized, open-label, single arm, multicenter, phase II study evaluating the

antitumor activity and safety of JDQ443 single agent as first-line treatment for participants

with locally advanced or metastatic KRAS G12C-mutated NSCLC. The study will have 2

non-comparative cohorts (Cohort A and B) that will recruit participants in parallel.

The study treatment begins on Cycle 1 Day 1 (C1D1) with the first administration of JDQ443.

Each cycle is 21 days.

Study completion is defined as the earliest occurrence of one of the following:

- The last participant completes last study visit (and the assessments associated with

this visit have been documented and followed-up appropriately by the Investigator),

dies, withdraws consent or is lost to follow-up, whichever comes first.

- In the event of an early study termination decision, the date of that decision.

- Another clinical study becomes available that can continue to provide JDQ443 to study

participants and all participants with ongoing treatment are transferred to that

clinical study.

Ein-/Ausschlusskriterien

Key Inclusion criteria

- Histologically confirmed locally advanced (stage IIIb/IIIc not eligible for definitive

chemoradiation or surgical resection with curative intent) or metastatic (stage IV)

NSCLC without previous systemic treatment for metastatic disease. Prior (neo)adjuvant

treatment with chemotherapy and/or immunotherapy, or prior radiotherapy administered

sequentially or concomitantly with chemotherapy and/or immunotherapy for localized or

locally advanced disease are accepted if the time between therapy completion and

enrollment is > 12 months.

- Presence of a KRAS G12C mutation (all participants) and:

- Cohort A: PD-L1 expression < 1%, regardless of STK11 mutation status

- Cohort B: PD-L1 expression ≥ 1% and an STK11 co-mutation

- At least one measurable lesion per RECIST 1.1.

- ECOG performance status ≤ 1.

- Participants capable of swallowing study medication.

Key Exclusion criteria

- Participants whose tumors harbor an EGFR-sensitizing mutation and/or ALK rearrangement

by local laboratory testing. Participants with other known druggable alterations will

be excluded, if required by local guidelines

- Previous use of a KRAS G12C inhibitor or previous systemic treatment for metastatic

NSCLC.

- A medical condition that results in increased photosensitivity (i.e. solar urticaria,

lupus erythematosus, etc).

- Know active (unstable/symptomatic) central nervous system (CNS) metastases and/or

carcinomatous meningitis

- Participants who are taking a prohibited medication (strong CYP3A inducers) that

cannot be discontinued at least seven days prior to the first dose of study treatment

and for the duration of the study

Other inclusion/exclusion criteria may apply

Studien-Rationale

Primary outcome:

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).

Studien-Arme

  • 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.

Geprüfte Regime

  • JDQ443:
    JDQ443 orally administered

Quelle: ClinicalTrials.gov


Sie können folgenden Inhalt einem Kollegen empfehlen:

"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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