HumRes60992
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SNCTP000005173
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BASEC2022-00920
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NCT05261399
Savolitinib plus Osimertinib versus platinum-based doublet chemotherapy in participants with EGFR-mutated, MET-overexpressing and/or amplified NSCLC who have progressed on Osimertinib
Zusammenfassung der Studie
The study investigates non-small cell lung cancer (NSCLC) that has progressed despite prior treatment with Osimertinib. The aim of this study is to find out whether the administration of Savolitinib in combination with Osimertinib is an effective treatment for NSCLC patients who have experienced disease progression while on Osimertinib alone. An equal number of patients in the main study will receive either Savolitinib in combination with Osimertinib or standard chemotherapy.
(BASEC)
Untersuchte Intervention
Savolitinib in combination with Osimertinib or standard chemotherapy.
(BASEC)
Untersuchte Krankheit(en)
Non-small cell lung cancer (NSCLC) that has progressed on treatment with Osimertinib.
(BASEC)
Kriterien zur Teilnahme
- Histologically or cytologically confirmed locally advanced or metastatic NSCLC that is not suitable for curative therapy. - Documented radiological progression under first or second line treatment with Osimertinib as the most recent cancer therapy. - Mandatory provision of FFPE tumor tissue. - MET gene elevation. - Adequate blood counts, liver and kidney values. - Pregnancy should be excluded. (BASEC)
Ausschlusskriterien
- NSCLC with predominant squamous cell histology for which Pemetrexed is not recommended. - Known transition to small cell lung cancer or presence of small cell elements. - Spinal cord compression or brain metastases. - Active tumor of the meninges. - Various heart diseases. - Major surgical procedures ≤ 28 days after the start of the study intervention or minor surgical procedures ≤ 7 days. - At the investigator's discretion, any evidence of severe or uncontrolled systemic diseases including active bleeding diathesis that would make patient participation in the study undesirable or would jeopardize adherence to the protocol. - Active Hepatitis B virus (HBV) - Known severe active infection, including tuberculosis or human immunodeficiency virus (HIV). - Receipt of a live attenuated vaccine (including against COVID-19) within 30 days prior to the first dose of the study intervention. - Presence of other active malignancies or a history of treatment for invasive malignancy within the last five years. - Prior allogeneic bone marrow transplantation. - For women only – the patient is currently pregnant (confirmed by a positive pregnancy test) or breastfeeding. (BASEC)
- Histologically or cytologically confirmed locally advanced or metastatic NSCLC that is not suitable for curative therapy. - Documented radiological progression under first or second line treatment with Osimertinib as the most recent cancer therapy. - Mandatory provision of FFPE tumor tissue. - MET gene elevation. - Adequate blood counts, liver and kidney values. - Pregnancy should be excluded. (BASEC)
Ausschlusskriterien
- NSCLC with predominant squamous cell histology for which Pemetrexed is not recommended. - Known transition to small cell lung cancer or presence of small cell elements. - Spinal cord compression or brain metastases. - Active tumor of the meninges. - Various heart diseases. - Major surgical procedures ≤ 28 days after the start of the study intervention or minor surgical procedures ≤ 7 days. - At the investigator's discretion, any evidence of severe or uncontrolled systemic diseases including active bleeding diathesis that would make patient participation in the study undesirable or would jeopardize adherence to the protocol. - Active Hepatitis B virus (HBV) - Known severe active infection, including tuberculosis or human immunodeficiency virus (HIV). - Receipt of a live attenuated vaccine (including against COVID-19) within 30 days prior to the first dose of the study intervention. - Presence of other active malignancies or a history of treatment for invasive malignancy within the last five years. - Prior allogeneic bone marrow transplantation. - For women only – the patient is currently pregnant (confirmed by a positive pregnancy test) or breastfeeding. (BASEC)
Studienstandort
Basel, Zürich
(BASEC)
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, France, Germany, Greece, Hong Kong, Israel, Italy, Japan, Korea, Republic of, Malaysia, Netherlands, Philippines, Poland, Russian Federation, Singapore, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States, Vietnam (ICTRP)
Sponsor
Fortrea Switzerland AG Verena Perneczky c/o Regus Badenerstr. 47 8004 Zürich
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
PD Dr. med. Dr. phil. nat. Sacha Rothschild
+41 61 265 50 74
sacha.rothschild@clutterusb.chKantonsspital Baden AG Zentrum Onkologie / Hämatologie Im Ergel 1 5404 Baden Schweiz
(BASEC)
Allgemeine Auskünfte
Shanghai Chest Hospital, Shanghai JiaoTong University, #241 Huai Hai Road (west), Shanghai, China.,
1-877-240-9479
sacha.rothschild@clutterusb.ch(ICTRP)
Wissenschaftliche Auskünfte
Shanghai Chest Hospital, Shanghai JiaoTong University, #241 Huai Hai Road (west), Shanghai, China.,
1-877-240-9479
sacha.rothschild@clutterusb.ch(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Nordwest- und Zentralschweiz EKNZ
(BASEC)
Datum der Bewilligung durch die Ethikkommission
13.10.2022
(BASEC)
ICTRP Studien-ID
NCT05261399 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
A Phase III, Randomised, Open-Label Study of Savolitinib in Combination With Osimertinib Versus Platinum-Based Doublet Chemotherapy in Participants With EGFR Mutated MET-Overexpressed and/or Amplified, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Progressed on Treatment With Osimertinib (SAFFRON) (BASEC)
Wissenschaftlicher Titel
A Phase III, Randomised, Open-Label Study of Savolitinib in Combination With Osimertinib Versus Platinum-Based Doublet Chemotherapy in Participants With EGFR Mutated, MET-Overexpressed and/or Amplified, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Progressed on Treatment With Osimertinib (SAFFRON). (ICTRP)
Öffentlicher Titel
Savolitinib Plus Osimertinib Versus Platinum-based Doublet Chemotherapy in Participants With Non-Small Cell Lung Cancer Who Have Progressed on Osimertinib Treatment (ICTRP)
Untersuchte Krankheit(en)
Carcinoma;Non-Small-Cell Lung (ICTRP)
Untersuchte Intervention
Drug: Savolitinib;Drug: Osimertinib;Drug: Pemetrexed;Drug: Cisplatin;Drug: Carboplatin (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Ein-/Ausschlusskriterien
Gender: All
Maximum age: 130 Years
Minimum age: 18 Years
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. (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
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. (ICTRP)
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.;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.;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.;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.;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.;Pharmacokinetics (PK) of savolitinib.;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 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;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.;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. (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Shun Lu, Prof,MD,PhD,;AstraZeneca Clinical Study Information Center, information.center@astrazeneca.com, 1-877-240-9479, Shanghai Chest Hospital, Shanghai JiaoTong University, #241 Huai Hai Road (west), Shanghai, China., (ICTRP)
Sekundäre IDs
2024-511169-12-00, 2021-006374-24, D5087C00001 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT05261399 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar