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.

JRCT ID: jRCT2031220420

Registered date:27/10/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Carcinoma, Non-Small-Cell Lung
• Date of first enrollment: 07/11/2022
• Target sample size: 324
• Countries of recruitment: Argentina,Japan,Australia,Japan,Austria,Japan,Belgium,Japan,Brazil,Japan,Bulgaria,Japan,Canada,Japan,Chile,Japan,China,Japan,France,Japan,Germany,Japan,Greece,Japan,Israel,Japan,Italy,Japan,Korea,Japan,Netherlands,Japan,Poland,Japan,Russia,Japan,Spain,Japan,Switzerland,Japan,Taiwan,Japan,Thailand,Japan,Turkey,Japan,UK,Japan,USA,Japan,Vietnam,Japan
• Study type: Interventional

Intervention(s)

Participants will be randomised in a ratio of 1:1 to receive oral treatment with 300 mg
savolitinib BID plus 80 mg osimertinib QD or platinum-based doublet chemotherapy
(cisplatin/carboplatin plus pemetrexed) via intravenous (IV) infusion on Day 1 of each 21-day
cycle for 4 cycles followed by pemetrexed maintenance therapy every 3 weeks (Q3W).

Outcome(s)

Primary Outcome

"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."

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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 or more 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.

Exclude 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 with the exception of alopecia, haemoglobin 9.0 g/dL or more, and Grade 2 prior platinum-therapy related neuropathy.

- 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.

Related Information

• Primary Sponsor: Hibi Kazushige
• Secondary ID(s): NCT05261399