Montag, 29. April 2024
Navigation öffnen
Anzeige:
Wefra Programatic
 
JOURNAL ONKOLOGIE – STUDIE
SAFFRON

Savolitinib Plus Osimertinib Versus Platinum-based Doublet Chemotherapy in Participants With Non-Small Cell Lung Cancer Who Have Progressed on Osimertinib Treatment

Rekrutierend

NCT-Nummer:
NCT05261399

Studienbeginn:
August 2022

Letztes Update:
03.04.2024

Wirkstoff:
Savolitinib, Osimertinib, Pemetrexed, Cisplatin, Carboplatin

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

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
AstraZeneca

Collaborator:
-

Studienleiter

Shun Lu, Prof,MD,PhD,
Principal Investigator
Shanghai Chest Hospital, Shanghai JiaoTong University, #241 Huai Hai Road (west), Shanghai, China.

Kontakt

AstraZeneca Clinical Study Information Center
Kontakt:
Phone: 1-877-240-9479
E-Mail: information.center@astrazeneca.com» Kontaktdaten anzeigen

Studienlocations
(3 von 273)

Research Site
60590 Frankfurt A. Main
(Hessen)
GermanyRekrutierend» Google-Maps
Research Site
74245 Löwenstein
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Research Site
48149 Muenster
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Research Site
70376 Stuttgart
(Baden-Württemberg)
GermanyZurückgezogen» Google-Maps
Research Site
88239 Wangen
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Research Site
92093 La Jolla
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
60805 Evergreen Park
United StatesZurückgezogen» Google-Maps
Research Site
X5004APD Cordoba
ArgentinaNoch nicht rekrutierend» Google-Maps
Research Site
4000 San Miguel de Tucumán
ArgentinaRekrutierend» Google-Maps
Research Site
29308-014 Cachoeiro de Itapemirim
BrazilRekrutierend» Google-Maps
Research Site
L5M 2N1 Mississauga
CanadaNoch nicht rekrutierend» Google-Maps
Research Site
33076 Bordeaux Cedex
FranceNoch nicht rekrutierend» Google-Maps
Research Site
641-8510 Wakayama-shi
JapanNoch nicht rekrutierend» Google-Maps
Research Site
13620 Gyeonggi-do
Korea, Republic ofRekrutierend» Google-Maps
Research Site
21431 Incheon
Korea, Republic ofNoch nicht rekrutierend» Google-Maps
Research Site
152703 Seoul
Korea, Republic ofNoch nicht rekrutierend» Google-Maps
Research Site
2600 Baguio City
PhilippinesNoch nicht rekrutierend» Google-Maps
Research Site
6000 Cebu City
PhilippinesNoch nicht rekrutierend» Google-Maps
Research Site
8000 Davao City
PhilippinesNoch nicht rekrutierend» Google-Maps
Research Site
1104 Quezon City
PhilippinesNoch nicht rekrutierend» Google-Maps
Research Site
1112 Quezon City
PhilippinesNoch nicht rekrutierend» Google-Maps
Research Site
1502 San Juan
PhilippinesNoch nicht rekrutierend» Google-Maps
Research Site
454087 Chelyabinsk
Russian FederationNoch nicht rekrutierend» Google-Maps
Research Site
197022 Saint Petersburg
Russian FederationZurückgezogen» Google-Maps
Research Site
634050 Tomsk
Russian FederationNoch nicht rekrutierend» Google-Maps
Research Site
169610 Singapore
SingaporeNoch nicht rekrutierend» Google-Maps
Research Site
308433 Singapore
SingaporeNoch nicht rekrutierend» Google-Maps
Research Site
CH-5405 Baden
SwitzerlandNoch nicht rekrutierend» Google-Maps
Research Site
83301 Kaohsiung City
TaiwanNoch nicht rekrutierend» Google-Maps
Research Site
BS2 8HW Bristol
United KingdomNoch nicht rekrutierend» Google-Maps
Research Site
WV10 0QP Wolverhampton
United KingdomRekrutierend» Google-Maps
Research Site
70000 Ho Chi Minh
VietnamNoch nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

This is a multicentre, Phase III, randomised, open-label study to investigate the efficacy

and safety of savolitinib administered orally in combination with osimertinib versus

platinum-based doublet chemotherapy in participants with EGFR mutated, MET-overexpressed

and/or amplified, locally advanced or metastatic NSCLC who have progressed on first- or

second-line treatment with osimertinib as the most recent therapy.

Approximately 324 participants with EGFR mutated, MET-overexpressed and/or amplified, locally

advanced or metastatic NSCLC will be randomly assigned to study intervention with 1:1 ratio.

Patients will be treated until either objective progression of disease (PD) by Response

Evaluation Criteria in Solid Tumours 1.1 (RECIST 1.1) is assessed by the investigator,

unacceptable toxicity occurs, consent is withdrawn, or another discontinuation criterion is

met.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Provision of signed and dated written ICF prior to any mandatory and non-mandatory

study-specific procedures, sampling and analyses.

- Participant must be ≥18 years (≥ 19 years of age in South Korea) at the time of

signing the informed consent. All genders are permitted.

- Histologically or cytologically confirmed locally advanced or metastatic NSCLC which

is not amenable to curative therapy.

- Must have at least one documented sensitising EGFR mutation: exon19 deletion, L858R

mutation, and/or T790M.

- Documented radiologic progression on first- or second-line treatment with osimertinib

as the most recent anti-cancer therapy.

- Mandatory provision of FFPE tumour tissue.

- MET overexpression and/or amplification in tumour specimen collected following

progression on prior osimertinib treatment.

- Measurable disease as defined by RECIST 1.1.

- Adequate haematological, liver, renal and cardiac functions, and coagulation

parameters.

- ECOG performance status of 0 or 1.

Exclusion Criteria:

- Predominant squamous NSCLC, and small cell lung cancer.

- Prior or current treatment with a third-generation EGFR-TKI other than Osimertinib.

- Prior or current treatment with savolitinib or another MET inhibitors.

- Spinal cord compression or brain metastases, unless asymptomatic and are stable.

- History or active leptomeningeal carcinomatosis.

- Unresolved toxicities from any prior therapy greater than CTCAE Grade 1 and prior

platinum-therapy related Grade 2 neuropathies with the exception of alopecia and

haemoglobin ≥ 9.0 g/dL.

- Active/unstable cardiac diseases currently or within the last 6 months, clinically

significant ECG abnormalities, and/or factors/medications that may affect QTc

intervals.

- History of liver cirrhosis of any origin and clinical stage; or history of other

serious liver disease or chronic disease with relevant liver involvement.

- Known serious active infection including, but not limited to, tuberculosis, or HIV,

HBV or HCV or gastrointestinal disease.

- Receipt of live attenuated vaccine (including against COVID-19) within 30 days prior

to the first dose of study intervention.

- Past medical history of ILD, drug-induced ILD, radiation pneumonitis, which required

steroid treatment, or any evidence of clinically active ILD.

- Participants currently receiving medications or herbal supplements known to be strong

inducers of cytochrome P450 (CYP)3A4 or strong inhibitors of CYP1A2.

Studien-Rationale

Primary outcome:

1. Progression-free survival (PFS) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on osimertinib. (Time Frame - Approximately 55 months post first subject randomized):
Defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.



Secondary outcome:

1. Overall Survival (OS) /savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib. (Time Frame - Approximately 55 months post first subject randomized.):
Defined as time from randomisation until the date of death due to any cause.

2. Progression-free survival (PFS) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed, locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib. (Time Frame - Approximately 55 months post first subject randomized):
Defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.

3. Overall Survival (OS) / savolitinib in combination with osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed by IHC, locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib. (Time Frame - Approximately 55 months post first subject randomized):
Defined as time from randomisation until the date of death due to any cause.

4. Objective response rate (ORR) savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib. (Time Frame - Approximately 55 months post first subject randomized):
ORR defined as the proportion of participants who have BOR of a CR or PR, as determined by BICR per RECIST 1.1.

5. Participant-reported pulmonary core symptoms / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on osimertinib. (Time Frame - Approximately 55 months post first subject randomized):
TTD in pulmonary core symptoms (dyspnoea, cough, and chest pain) as measured by the NSCLC-SAQ. TTD is defined as the time from randomisation until the date of deterioration.

6. Pharmacokinetics (PK) of savolitinib. (Time Frame - 6 weeks after last patient dosed):
Plasma concentrations of savolitinib and its metabolites.

7. Disease control rate (DCR) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib. (Time Frame - Approximately 55 months post first subject randomized):
DCR defined as the proportion of participants who have BOR of a CR, PR, or stable disease, as determined by BICR per RECIST 1.1.

8. Time to discontinuation of treatment (TDT) or death / savolitinib + osimertinib vs platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on osimertinib (Time Frame - Approximately 55 months post first subject randomized):
TDT or death is defined as the time from date of randomisation to the earlier of the date of study intervention discontinuation or death.

9. Tumor shrinkage / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib. (Time Frame - Approximately 55 months post first subject randomized):
Tumour shrinkage defined as percentage change in tumour size in accordance with RECIST 1.1.

10. Duration of response (DoR) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib. (Time Frame - Approximately 55 months post first subject randomized):
DoR defined as the time from the date of first documented response until date of documented progression per RECIST 1.1 as assessed by BICR, or death in the absence of disease progression.

Studien-Arme

  • Active Comparator: Chemotherapy
    Pemetrexed (500 mg/m2) with either cisplatin (75 mg/m2) or carboplatin (AUC5) on Day 1 of 21-day cycles (Q3W) for 4 cycles, followed by pemetrexed maintenance (500 mg/m2) Q3W
  • Experimental: Savolitinib + Osimertinib
    300 mg savolitinib BID plus 80 mg osimertinib QD

Geprüfte Regime

  • Savolitinib (AZD6094, HMPL-504, volitinib):
    300 mg savolitinib (3 × 100 mg tablets twice daily) Administrative route : oral
  • Osimertinib (AZD9291, Tagrisso):
    80 mg osimertinib (1 × 80 mg tablet once daily) Administrative route : oral
  • Pemetrexed (NAP):
    Pemetrexed (500 mg/m2) Administrative route : IV infusion
  • Cisplatin (NAP):
    Cisplatin (75 mg/m2) or Administrative route : IV infusion
  • Carboplatin (NAP):
    Carboplatin (AUC5) Administrative route : IV infusion

Quelle: ClinicalTrials.gov


Sie können folgenden Inhalt einem Kollegen empfehlen:

"Savolitinib Plus Osimertinib Versus Platinum-based Doublet Chemotherapy in Participants With Non-Small Cell Lung Cancer Who Have Progressed on Osimertinib Treatment"

Bitte tragen Sie auch die Absenderdaten vollständig ein, damit Sie der Empfänger erkennen kann.

Die mit (*) gekennzeichneten Angaben müssen eingetragen werden!

Die Verwendung Ihrer Daten für den Newsletter können Sie jederzeit mit Wirkung für die Zukunft gegenüber der MedtriX GmbH - Geschäftsbereich rs media widersprechen ohne dass Kosten entstehen. Nutzen Sie hierfür etwaige Abmeldelinks im Newsletter oder schreiben Sie eine E-Mail an: rgb-info[at]medtrix.group.