Purpose

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.

Conditions

Eligibility

Eligible Ages
Between 18 Years and 130 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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
    Other names:
    • NAP
  • Drug: Cisplatin
    Cisplatin (75 mg/m2) or Administrative route : IV infusion
    Other names:
    • NAP
  • Drug: Carboplatin
    Carboplatin (AUC5) Administrative route : IV infusion
    Other names:
    • NAP
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
    Other names:
    • AZD6094, HMPL-504, volitinib
  • Drug: Osimertinib
    80 mg osimertinib (1 × 80 mg tablet once daily) Administrative route : oral
    Other names:
    • AZD9291, Tagrisso

Recruiting Locations

Research Site
Nashville, Tennessee 37232

More Details

Status
Recruiting
Sponsor
AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.