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JOURNAL ONKOLOGIE – STUDIE

GeoMETry-III Study of Capmatinib Efficacy in Comparison With Docetaxel in Previously Treated Participants With Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation

Rekrutierend

NCT-Nummer:
NCT04427072

Studienbeginn:
September 2020

Letztes Update:
08.01.2021

Wirkstoff:
Capmatinib, Docetaxel

Indikation (Clinical Trials):
Carcinoma, Non-Small-Cell Lung

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Novartis Pharmaceuticals

Collaborator:
-

Studienleiter

Novartis Pharmaceuticals
Study Director
Novartis Pharmaceuticals

Kontakt

Novartis Pharmaceuticals

Studienlocations (3 von 21)

Novartis Investigative Site
93053 Regensburg
(Bayern)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
13125 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
60488 Frankfurt
(Hessen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
50937 Koeln
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
49933 Angers Cedex 9
FranceRekrutierend» Google-Maps
Novartis Investigative Site
63011 Clermont-Ferrand
FranceRekrutierend» Google-Maps
Novartis Investigative Site
69495 Pierre Benite
FranceRekrutierend» Google-Maps
Novartis Investigative Site
2045 Torokbalint
HungaryRekrutierend» Google-Maps
Novartis Investigative Site
05505 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Novartis Investigative Site
603081 Nizhniy Novgorod
Russian FederationRekrutierend» Google-Maps
Novartis Investigative Site
644013 Omsk
Russian FederationRekrutierend» Google-Maps
Novartis Investigative Site
196603 Pushkin Saint Petersburg
Russian FederationRekrutierend» Google-Maps
Novartis Investigative Site
197022 St- Petersburg
Russian FederationRekrutierend» Google-Maps
Novartis Investigative Site
08907 Hospitalet de LLobregat
SpainRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

Participants eligible for the study will be randomized in a 2:1 ratio to one of the two

treatment arms: capmatinib (investigational therapy) or docetaxel. The randomization will be

stratified by prior lines of systemic therapy received for advanced/metastatic disease (one

line vs. two lines).

For all participants, the respective treatment (either with capmatinib or docetaxel) may be

continued beyond initial disease progression as per RECIST 1.1 (as assessed by the

investigator and confirmed by BIRC) if, in the judgment of the investigator, there is

evidence of clinical benefit, and the participant wishes to continue on the study treatment.

After treatment discontinuation, all participants will be followed for safety evaluations

during the safety follow-up period, and the participant's status will be collected every 12

weeks as part of the survival follow-up.

Participants randomized to docetaxel treatment will be eligible to crossover to receive

capmatinib treatment after BIRC-confirmed, RECIST 1.1-defined progressive disease and after

meeting the eligibility criteria prior to crossover.

The primary objective of this study is to compare the efficacy of capmatinib versus docetaxel

by comparing progression-free survival (PFS) by blinded independent review committee (BIRC)

according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 between treatment

arms.

Ein-/Ausschlusskriterien

Key Inclusion Criteria:

- Stage IIIB/IIIC (not amenable to surgery, radiation or multi modality therapy) or IV

NSCLC (according to Version 8 of the American Joint Committee on Cancer (AJCC) Staging

Manual) at the time of study entry.

- Histologically or cytologically confirmed diagnosis of NSCLC that is:

1. EGFR wt. Assessed as part of participant's standard of care by a validated test

for EGFR mutations as per local guidelines. The EGFR wt status (for EGFR

mutations that predict sensitivity to EGFR therapy, including, but not limited to

exon 19 deletions and exon 21 L858R substitution mutations.

2. AND ALK rearrangement negative. Assessed as part of participant's standard of

care by a validated test.

3. AND has METΔex14 mutation per Novartis-designated central laboratory.

- Mandatory provision of a formalin-fixed, paraffin embedded tumor tissue sample

(archival tumor block or slides, or a newly obtained tumor sample)

- Progressed on one or two prior lines of systemic therapy for advanced/metastatic

disease (stage IIIB/IIIC [not candidates for surgery, radiation or multi modality

therapy] or IV NSCLC) and must be candidates for single agent chemotherapy

(docetaxel).

- At least one measurable lesion as defined by RECIST 1.1

- Adequate organ function

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.

Key Exclusion Criteria:

- Prior treatment with any MET inhibitor or HGF-targeting therapy.

- Participants with symptomatic central nervous system (CNS) metastases who are

neurologically unstable or have required increasing doses of steroids within the 2

weeks prior to study entry to manage CNS symptoms.

- Participants with known druggable molecular alterations (such as ROS1 translocation or

BRAF mutation, etc.) which might be a candidate for alternative targeted therapies as

applicable per local regulations and treatment guidelines.

- Presence or history of interstitial lung disease or interstitial pneumonitis,

including clinically significant radiation pneumonitis (i.e., affecting activities of

daily living or requiring therapeutic intervention).

- Substance abuse, active infection or other severe, acute, or chronic medical or

psychotic conditions or laboratory abnormalities that in the opinion of the

investigator may increase the risk associated with study participation

Other protocol-defined inclusion/exclusion criteria may apply.

Studien-Rationale

Primary outcome:

1. Progression free survival (PFS) per blinded independent review committee (BIRC) using RECIST v1.1 (Time Frame - From randomization to the date of first documented progression or death from any cause, whichever comes first, assessed up to approximately 21 months):
Progression free survival is defined as the time from the date of randomization to the date of the first documented progression assessed by BIRC according to RECIST 1.1, or death due to any cause



Secondary outcome:

1. Overall response (ORR) per RECIST 1.1 by BIRC (Time Frame - Up to approximately 21 months):
Proportion of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR), assessed by BIRC according to RECIST 1.1.

2. Overall response (ORR) per RECIST 1.1 by investigator (Time Frame - Up to approximately 21 months):
Proportion of participants with confirmed BOR of CR or PR, assessed by local review according to RECIST 1.1.

3. Time to response (TTR) per RECIST 1.1 by BIRC (Time Frame - From date of randomization to first documented response of either CR or PR, assessed up to approximately 21 months):
Time from date of randomization to first documented response of either CR or PR, which must be subsequently confirmed, assessed by BIRC according to RECIST 1.1.

4. Time to response (TTR) per RECIST 1.1 by investigator (Time Frame - From date of randomization to first documented response of either CR or PR, assessed up to approximately 21 months):
Time from date of randomization to first documented response of either CR or PR, which must be subsequently confirmed, assessed by local review according to RECIST 1.1.

5. Duration of response (DOR) per RECIST 1.1 by BIRC (Time Frame - From first documented response to first documented progression or death due to any cause, whichever comes first, assessed up to approximately 21 months):
Time from the date of first documented response (CR or PR) to the first documented progression by BIRC per RECIST 1.1 or death due to any cause.

6. Duration of response (DOR) per RECIST 1.1 by investigator (Time Frame - From first documented response to first documented progression or death due to any cause, whichever comes first, assessed up to approximately 21 months):
Time from the date of first documented response (CR or PR) to the first documented progression by local review per RECIST 1.1 or death due to any cause.

7. Disease Control Rate (DCR) per RECIST 1.1 by BIRC (Time Frame - Up to approximately 21 months):
Proportion of participants with a BOR of confirmed CR, PR and stable disease (SD) assessed by BIRC according to RECIST 1.1

8. Disease Control Rate (DCR) per RECIST 1.1 by investigator (Time Frame - Up to approximately 21 months):
Proportion of participants with a BOR of confirmed CR, PR and SD assessed by local review according to RECIST 1.1

9. Progression free survival (PFS) per investigator using RECIST v1.1 (Time Frame - From randomization to the date of first documented progression or death from any cause, whichever comes first, assessed up to approximately 21 months):
Time from the date of randomization to the date of the first documented progression assessed by local review according to RECIST 1.1, or death due to any cause

10. Overall survival (OS) (Time Frame - From randomization to death due to any cause, assessed up to approximately 42 months):
OS is defined as the time from the date of randomization to the date of death due to any cause.

11. Percentage of patients with Adverse Events and Serious Adverse events. (Time Frame - Up to approximately 42 months):
Safety profile of capmatinib. Incidence of Adverse Events and Serious Adverse events, including abnormal laboratory values or test results.

12. Plasma capmatanib concentration (Time Frame - Cycle (C) 1 Day (D) 15 pre-dose, 1 and 4 hours post-dose, C3 D1 pre-dose. Each cycle duration is 21 days.):
Plasma concentrations of capmatinib. Blood samples will be collected at indicated time points for pharmacokinetic analysis.

13. Change from baseline in score as per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 (Time Frame - Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months. Each cycle duration is 21 days.):
EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients.

14. Change from baseline in score as per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Lung Cancer Module (QLQ-LC13) (Time Frame - Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months. Each cycle duration is 21 days.):
EORTC QLQ-LC13 is a 13-item lung cancer specific questionnaire.

15. Change from baseline in score as per European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) questionnaire (Time Frame - Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months. Each cycle duration is 21 days.):
EQ-5D-5L is a standardized measure to assess the overall health-related quality of life in patients.

16. Overall intracranial response rate (OIRR) (Time Frame - Up to approximately 21 months):
Proportion of participants with confirmed best overall intracranial response (BOIR) of CR or partial response (PR), as assessed by BIRC review per RANO-BM criteria.

17. Duration of intracranial response (DOIR) (Time Frame - From date of first documented intracranial response (CR or PR) to first documented intracranial progression, assessed up to approximately 21 months):
Time from date of first documented intracranial response (CR or PR) to first documented intracranial progression per RANO-BM or date of death due to underlying cause of cancer.

18. Time to intracranial response (TTIR) (Time Frame - From date of randomization to first documented intracranial response of either CR or PR, assessed up to approximately 21 months):
Time from date of randomization to first documented intracranial response of either CR or PR, per RANO-BM criteria and assessed by BIRC, which must be subsequently confirmed.

19. Intracranial disease control rate (IDCR) (Time Frame - Up to approximately 21 months):
Proportion of participants with a BOR of confirmed CR, PR and stable disease (SD) (or non-CR/non-PD) per RANO-BM, assessed by BIRC.

Studien-Arme

  • Experimental: Capmatinib
    400mg of capmatinib tablets, administered orally twice daily
  • Active Comparator: Docetaxel
    Docetaxel 75 mg/m2 solution administered by intravenous infusion on Day 1 of every 21-day cycle

Geprüfte Regime

  • Capmatinib (INC280):
    400mg of capmatinib tablets administered orally twice daily
  • Docetaxel:
    Docetaxel 75 mg/m2 by intravenous infusion every 21 days

Quelle: ClinicalTrials.gov


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