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Non-Small Cell Lung CancerPhase 2CoCNCT04606771

A Study Comparing Savolitinib Plus Osimertinib vs Savolitinib Plus Placebo in Patients With EGFRm+ and MET Amplified Advanced NSCLC

A Phase 2 study testing Osimertinib + Savolitinib in people with Non-Small Cell Lung Cancer, run by AstraZeneca at 21 sites in 6 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This study will compare the activity of the combination of savolitinib and osimertinib against the combination of savolitinib with placebo to osimertinib in patients with Epidermal Growth Factor Receptor Mutation Positive and MET amplified, locally advanced or metastatic non-small cell lung cancer who have progressed… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Small Cell Lung Cancer
What is being tested?
Osimertinib + Savolitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
30 participants
Where
21 sitesin 6 countries
Study dates
28 Sep 2020to 15 Mar 2027
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must be ≥ 18 years of age at the time of signing the informed consent (≥ 20 years of age in Japan). All genders are permitted
  • Histologically or cytologically confirmed locally advanced or metastatic EGFRm+ NSCLC harbouring an EGFR mutation known to be associated with EGFR TKI sensitivity and that is permitted in the osimertinib national label (such as exon 19 deletion and/or L858R), which is not amenable to curative therapy.
  • Documented radiologic PD following treatment with osimertinib (osimertinib does not need to be the most recent therapy).
  • Have MET amplification as determined by central MET FISH testing on tumour specimen collected following progression on prior osimertinib treatment.
  • At least measurable target lesion
  • Patients must have received at least one but no more than 3 prior lines of therapy (including investigational therapy) in the locally advanced/metastatic setting.
Show all 10Show fewer
  • Adequate haematological, liver and renal function
  • Eastern Cooperative Oncology Group/WHO performance status of 0 or 1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.
  • Females of childbearing potential should be willing to use adequate contraceptive measures, should not be breastfeeding, and must have a negative pregnancy test.
  • Male patients with a female partner of childbearing potential should be willing to use barrier contraception during the study and for 6 months following discontinuation of study intervention. Patients should refrain from donating sperm from the start of dosing until 6 months after discontinuing study intervention.

Who cannot join

  • Unresolved toxicities from any prior therapy greater than CTCAE Grade 1 at the time of starting study intervention with the exception of alopecia, haemoglobin ≥ 9 g/dL and Grade 2, prior platinum therapy related neuropathy.
  • As judged by the investigator, active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy.
  • Any of the following cardiac diseases currently or within the last 6 months:
  • Unstable angina pectoris
  • Congestive heart failure (NYHA Grade ≥ 2)
  • Acute myocardial infarction
Show all 27Show fewer
  • Stroke or transient ischemic attack
  • Uncontrolled hypertension (BP ≥ 150/95 mmHg despite medical therapy).
  • Mean resting corrected QT interval (QTcF) > 470 msec for women and > 450 msec for men at Screening, obtained from 3 ECGs using the screening clinic ECG machine derived QTcF value.
  • Any factors that may increase the risk of QTcF prolongation or risk of arrhythmic events
  • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECGs.
  • Acute coronary syndrome
  • Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤ 28 days or limited field radiation for palliation ≤ 7 days prior to starting study intervention or has not recovered from side effects of such therapy.
  • Major surgical procedures ≤ 28 days of beginning study intervention or minor surgical procedures ≤ 7 days. No waiting is required following port-a-cath placement.
  • As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including renal transplant or active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to enter the study or which would jeopardise compliance with the CSP.
  • Active HBV (positive HBsAg result) or HCV. Viral testing is not required for assessment of eligibility for the study.
  • Known serious active infection including, but not limited to, tuberculosis, or HIV (positive HIV 1/2 antibodies). Testing is not required for assessment of eligibility for the study.
  • Presence of other active cancers, or history of treatment for invasive cancer, within the last 5 years. Patients with Stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (ie, non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
  • Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 2 weeks prior to start of study intervention.
  • Past medical history of ILD, drug-induced ILD, radiation pneumonitis, which required steroid treatment, or any evidence of clinically active ILD.
  • Prior or current treatment with a 3rd generation EGFR-TKI other than osimertinib.
  • Prior or current treatment with savolitinib or another MET inhibitor (for example, foretinib, crizotinib, cabozantinib, onartuzumab, capmatinib).
  • Patients who have received ≥ 4 lines of systemic therapy for NSCLC
  • Any cytotoxic chemotherapy, investigational agents or other anti cancer drugs for the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days prior to the first dose of study intervention with the exception of monotherapy osimertinib which may continue uninterrupted during screening.
  • Patients currently receiving (or unable to stop use prior to receiving the first dose of study intervention) medications or herbal supplements known to be strong inducers of CYP3A4 or strong inhibitors of CYP1A2, or CYP3A4 substrates which have a narrow therapeutic range within 2 weeks of the first dose of study intervention (3 weeks for St John's Wort) will be excluded. All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4 during the study and for 3 months later the last dose intake.
  • Participation in another clinical study with a cytotoxic, investigational product, or other anti cancer drug for the treatment of advanced NSCLC if received study intervention from that study within 14 days of the first dose of study intervention.
  • Known hypersensitivity to the active or inactive excipients of osimertinib or savolitinib or drugs with a similar chemical structure or class.

Trial locations and contacts

21 sites in 6 countries.

21 sites in 6 countries

Thailand8 sites

  • Research Site

    Bangkok, 10210

  • Research Site

    Bangkok, 10300

  • Research Site

    Bangkok, 10330

  • Research Site

    Bangkok, 10400

  • Research Site

    Bangkok, 10700

  • Research Site

    Hat Yai, 90110

  • Research Site

    Khon Kaen, 40002

  • Research Site

    Muang, 50200

Other trials in Thailand

Taiwan5 sites

  • Research Site

    Taichung, 402

  • Research Site

    Taipei, 100

  • Research Site

    Taipei, 11217

  • Research Site

    Taipei, 235

  • Research Site

    Taoyuan City, 333

Other trials in Taiwan

Vietnam3 sites

  • Research Site

    Hà Nội, 100000

  • Research Site

    Hanoi, 100000

  • Research Site

    Ho Chi Minh City, 700000

Other trials in Vietnam

United States2 sites

  • Research Site

    Duarte, California, 91010

  • Research Site

    Sacramento, California, 95817

Other trials in United States

India2 sites

  • Research Site

    Delhi, 110085

  • Research Site

    Mumbai, 400053

Other trials in India

Argentina1 site

  • Research Site

    Ciudad de Buenos Aires, C1120AAT

Other trials in Argentina

About this study

Official title: A Multi-centre Phase II, Double-Blind, Randomised Study of Savolitinib in Combination With Osimertinib vs Savolitinib in Combination With Placebo in Patients With EGFRm+ and MET Amplified Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Progressed Following Treatment With Osimertinib

This study will compare the activity of the combination of savolitinib and osimertinib against the combination of savolitinib with placebo to osimertinib in patients with Epidermal Growth Factor Receptor Mutation Positive and MET amplified, locally advanced or metastatic non-small cell lung cancer who have progressed following treatment with osimertinib.

Read the detailed description

Resistance to EGFR-TKIs is a clinical problem. One of the mechanisms for resistance to osimertinib is amplification of the MET receptor tyrosine kinase, which activates downstream intracellular signalling independent of EGFR. This study will explore the individual contribution of savolitinib to MET mediated osimertinib resistance, by assessing the response to dual pathway blockade of EGFRm and MET to overcome MET mediated resistance to osimertinib versus inhibition of the MET pathway alone by investigating the efficacy of savolitinib plus osimertinib versus savolitinib plus placebo to osimertinib (hereafter referred to as placebo) in patients with EGFRm+ and MET amplified, locally advanced or metastatic NSCLC who have progressed following treatment with osimertinib. This is a multi centre, Phase II, double blind, randomised study.

Patients will be randomised in a ratio of 1:1 to receive treatment with savolitinib once daily plus osimertinib once daily or savolitinib once daily plus placebo. Randomisation will be stratified according to the number ofprior lines of therapy (ie, osimertinib monotherapy as first line or ≥ second line [which includes patients who received osimertinib monotherapy before or after chemotherapy]). All patients confirmed as eligible will begin treatment on Day 1 with savolitinib plus osimertinib or savolitinib plus placebo. Treatment will continue once daily in 28 day cycles until either objective PD by RECIST 1.1 is assessed, unacceptable toxicity occurs, consent is withdrawn, or another discontinuation criterion is met.

After progression, patients can be unblinded, and patients initially randomised to the savolitinib plus placebo arm may cross-over to open-label savolitinib plus osimertinib following investigator assessed objective PD to ensure that all patients enrolled may have the opportunity to receive the combination of savolitinib plus osimertinib.

Being tested
Osimertinib + Savolitinib, Savolitinib + Placebo
Keywords
Locally, Advanced, Metastatic, Carcinoma, Non-Small Cell Lung Cancer, Osimertinib, Tagrisso, Savolitinib, MET, EGFR
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis, Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Osimertinib + SavolitinibDrug

    Osimertinib 80 mg oral QD

    Savolitinib 300mg oral QD

  • Savolitinib + PlaceboDrug

    Savolitinib 300mg Oral QD

    Placebo to Osimertinib 80mg oral QD

Study groups in NCT04606771
Study groupRoleWhat they receive
Arm AExperimentalSavolitinib 300 mg oral QD Osimertinib 80 mg oral QD
Receives: Drug: Osimertinib + Savolitinib
Arm BExperimentalSavolitinib 300 mg oral QD Placebo to Osimertinib 80mg oral QD
Receives: Drug: Savolitinib + Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR)

    Percentage of evaluable patients with an Investigator-assessed visit response of complete response (CR) or partial response (PR). CR defined as disappearance of all target and non-target lesions and no new lesions. PR defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesions. Overall Response (OR) = CR + PR.

    Measured: Tumour assessments every 6 weeks from randomisation up to 24 weeks, then every 8 weeks until objective disease progression (maximum of approximately 25 months)

Secondary outcomes (11)

  1. Progression-free Survival (PFS)

    PFS is defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression. Progression (i.e., PD) is defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of ≥5mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters.

    Measured: Tumour assessments every 6 weeks from randomisation up to 24 weeks, then every 8 weeks until objective disease progression (maximum of approximately 25 months)

  2. Duration of Response (DoR)

    DoR is defined as the time from the date of first documented response until date of documented progression per RECIST 1.1 as assessed by the investigator or death in the absence of disease progression.

    Measured: Tumour assessments every 6 weeks from randomisation up to 24 weeks, then every 8 weeks until objective disease progression (maximum of approximately 25 months)

  3. Tumour Size Assessment (TSA)

    TSA is defined as the percentage change from baseline in TLs at 12 weeks per RECIST 1.1 as assessed by the investigator.

    Measured: Baseline and 12 weeks.

  4. Overall Survival (OS)

    OS is defined as time from randomisation until the date of death due to any cause.

    Measured: From the date of randomisation until death due to any cause, assessed up to the data cut-off date (21 December 2022) (maximum of approximately 25 months)

  5. Total Clearance in EGFR Mutations at 6-weeks After Therapy Initiation (Percentage Change From Baseline in EGFR Mutation Allele Frequencies).

    To determine the prevalence of ctDNA clearance after savolitinib plus osimertinib or savolitinib plus placebo treatment in this patient population

    Measured: 6-weeks after therapy initiation.

  6. Total Clearance in EGFR Mutations at 6-weeks After Therapy Initiation (Absolute Change From Baseline in EGFR Mutation Allele Frequencies).

    To determine the prevalence of ctDNA clearance after savolitinib plus osimertinib or savolitinib plus placebo treatment in this patient population

    Measured: 6-weeks after therapy initiation.

  7. PK Concentration Ratios on Multiple Dosing

    The time dependency of the PK on multiple dosing is assessed by the ratio of mean concentrations at the timepoints identified in column one. For example, the Geometric mean ratio for "C3h Cycle2 Day 1 / C3h Cycle 1 Day 1" periods is the geometric mean value for C3h Cycle 2 Day 1 (Stage 2) divided by the geometric mean value for C3h Cycle 1 Day 1 (Stage 1). Because the measurement is a ratio of values, no measures of central tendency are appropriate.

    Measured: C3h Cycle 2 Day 1/C3h Cycle 1 Day 1; Cpre-dose Cycle 3 Day 1/Cpre-dose Cycle 2 Day 1; Cpre-dose Cycle 6 Day 1/Cpre-dose Cycle 2 Day 1; Cpre-dose Cycle 11 Day 1/Cpre-dose Cycle 2 Day 1. (Each Cycle is 28 days)

  8. AUCss of Savolitinib, Osimertinib and Their Metabolites, (M2 and M3 for Savolitinib; AZ5104 for Osimertinib)

    Area under the plasma concentration-time curve at steady state

    Measured: Cycle 3, Day 1: Pre-dose and 1, 3, 4, and 6 hours post-dose

  9. Cssmax of Savolitinib, Osimertinib and Their Metabolites, (M2 and M3 for Savolitinib; AZ5104 for Osimertinib)

    Maximum steady state plasma concentration

    Measured: Cycle 3, Day 1: Pre-dose and 1, 3, 4, and 6 hours post-dose

  10. Tssmax of Savolitinib, Osimertinib and Their Metabolites, (M2 and M3 for Savolitinib; AZ5104 for Osimertinib)

    Time to maximum plasma concentration at steady state

    Measured: Cycle 3, Day 1: Pre-dose and 1, 3, 4, and 6 hours post-dose

  11. CLss/F of Savolitinib, Osimertinib and Their Metabolites, (M2 and M3 for Savolitinib; AZ5104 for Osimertinib)

    To evaluate the PK of savolitinib and osimertinib.

    Measured: Cycle 3, Day 1 (Each Cycle is 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Oct 2020
  2. Study start28 Sep 2020
  3. Primary completion21 Dec 2022
  4. Study completion15 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
1. Patients will take savolitinib 300mg tablets QD within 15 minutes after the start of a meal except for the day on which PK samples are taken. Patients will take osimertinib 80mg tablet once daily with/without food except for the day on which PK samples are taken. On the day when PK samples are taken both savolitinib \& osimertinib will be administered after a meal prepared by the clinic 2. Patients will take savolitinib 300mg tablets QD within 15 minutes after the start of a meal except for the day on which PK samples are taken. Patients will take placebo to osimertinib 80mg tablet once daily with/without food except for the day on which PK samples are taken. On the day when PK samples are taken both savolitinib \& placebo to osimertinib will be administered within 15 minutes after a meal prepared by the clinic In addition to comparing the ORR between groups, this study will also assess safety and tolerability, DoR, DCR, OS, PFS and other measures of antitumor activity
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04606771
Sponsor's protocol ID
D5084C00009
Acronym
CoC
Status last verified
Jul 2026
First submitted
1 Sep 2020
Last updated
30 Jul 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Osimertinib + Savolitinib in people with Non-Small Cell Lung Cancer, run by AstraZeneca at 21 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in Thailand, Taiwan, Vietnam, United States, India and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: Tumour assessments every 6 weeks from randomisation up to 24 weeks, then every 8 weeks until objective disease progression (maximum of approximately 25 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04606771.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2026.

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