Save

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

PHASE3RECRUITING

Clinical study to investigate the efficacy and safety 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 NSCLC who have progressed on treatment with Osimertinib.

Simpliy with AI

Study details:

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1 (RECIST 1. 1) is assessed by the investigator, unacceptable toxicity occurs, consent is withdrawn, or another discontinuation criterion is met.

Simplify with AI

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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.

Simplify with AI

Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2022-08-03

Primary completion: 2025-06-26

Study completion finish: 2026-12-17

Study type

TREATMENT

Phase

PHASE3

Trial ID

NCT05261399

Intervention or treatment

DRUG: Savolitinib

DRUG: Osimertinib

DRUG: Pemetrexed

DRUG: Cisplatin

DRUG: Carboplatin

Conditions

• Carcinoma
• Non-Small-Cell Lung

Condition: Carcinoma, Non-Small-Cell Lung
DRUG: Savolitinib and other drugs
Clayton, Not Specified, Australia and more
Sponsor: AstraZeneca

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Research Site

Research sites nearby

Select from list below to view details:

Research Site
Clayton, Not Specified, Australia
Research Site
Liverpool, Not Specified, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
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	DRUG: Pemetrexed Pemetrexed (500 mg/m2) Administrative route : IV infusion
EXPERIMENTAL: Savolitinib + Osimertinib 300 mg savolitinib BID plus 80 mg osimertinib QD	DRUG: Savolitinib 300 mg savolitinib (3 × 100 mg tablets twice daily) Administrative route : oral

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
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.	Defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.	Approximately 55 months post first subject randomized

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
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.	Defined as time from randomisation until the date of death due to any cause.	Approximately 55 months post first subject randomized.
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.	Defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.	Approximately 55 months post first subject randomized
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.	Defined as time from randomisation until the date of death due to any cause.	Approximately 55 months post first subject randomized
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.	ORR defined as the proportion of participants who have BOR of a CR or PR, as determined by BICR per RECIST 1.1.	Approximately 55 months post first subject randomized
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.	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.	Approximately 55 months post first subject randomized
Pharmacokinetics (PK) of savolitinib.	Plasma concentrations of savolitinib and its metabolites.	6 weeks after last patient dosed
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.	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.	Approximately 55 months post first subject randomized
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	TDT or death is defined as the time from date of randomisation to the earlier of the date of study intervention discontinuation or death.	Approximately 55 months post first subject randomized
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.	Tumour shrinkage defined as percentage change in tumour size in accordance with RECIST 1.1.	Approximately 55 months post first subject randomized
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.	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.	Approximately 55 months post first subject randomized

Frequently Asked Questions

Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol

No questions submitted. Be the first to ask a question!

You may be eligible to participate in this trial based on your search.Apply for study

Are you running this trial? If you're a clinic or sponsor, you can claim this study.Claim this trial

References

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