We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04606771
Recruitment Status : Active, not recruiting
First Posted : October 28, 2020
Last Update Posted : September 8, 2022
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief 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 following treatment with osimertinib.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: Osimertinib + Savolitinib Drug: Savolitinib + Placebo Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : September 28, 2020
Estimated Primary Completion Date : December 21, 2022
Estimated Study Completion Date : December 20, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Osimertinib

Arm Intervention/treatment
Experimental: Arm A

Savolitinib 300 mg oral QD

Osimertinib 80 mg oral QD

Drug: Osimertinib + Savolitinib

Osimertinib 80 mg oral QD

Savolitinib 300mg oral QD


Experimental: Arm B

Savolitinib 300 mg oral QD

Placebo to Osimertinib 80mg oral QD

Drug: Savolitinib + Placebo

Savolitinib 300mg Oral QD

Placebo to Osimertinib 80mg oral QD





Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: The primary analysis will occur 6 months after the last patient is randomised. ]
    ORR will be performed based on Investigator assessment of disease progression by RECIST 1.1.


Secondary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: The primary analysis will occur 6 months after the last patient is randomised. ]
    PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by the investigator or death due to any cause.

  2. Duration of Response (DoR) [ Time Frame: The primary analysis will occur 6 months after the last patient is randomised. ]
    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.

  3. Tumour Size Assessment (TSA) [ Time Frame: The primary analysis will occur 6 months after the last patient is randomised. ]
    TSA is defined as the percentage change from baseline in TLs at 12 weeks per RECIST 1.1 as assessed by the investigator.

  4. Overall Survival (OS) [ Time Frame: The primary analysis will occur 6 months after the last patient is randomised. the final analysis will occur at the earlier of 18 months after the last patient is randomised or when 70% of patients have progressed or died. ]
    OS is defined as time from randomisation until the date of death due to any cause.

  5. Objective Response Rate (ORR) [ Time Frame: The primary analysis will occur 6 months after the last patient is randomised. the final analysis will occur at the earlier of 18 months after the last patient is randomised or when 70% of patients have progressed or died. ]
    Objective response rate in patients who cross over after progression on savolitinib plus placebo, defined as the proportion of patients with measurable disease who have a CR or PR as determined by the investigator at the local site per RECIST 1.1.

  6. Progression Free Survival [ Time Frame: The primary analysis will occur 6 months after the last patient is randomised. the final analysis will occur at the earlier of 18 months after the last patient is randomised or when 70% of patients have progressed or died. ]
    Progression free survival in patients who cross over after progression on savolitinib plus placebo, defined as time from the first dose in the cross over period until progression per RECIST 1.1 as assessed by the investigator or death due to any cause.

  7. Duration of Response [ Time Frame: The primary analysis will occur 6 months after the last patient is randomised. the final analysis will occur at the earlier of 18 months after the last patient is randomised or when 70% of patients have progressed or died. ]
    Duration of response in patients who cross over after progression on savolitinib plus placebo, defined as the time from the date of first documented response during the cross-over period until date of documented progression per RECIST 1.1 as assessed by the investigator or death in the absence of disease progression.

  8. Tumour Size Assessment [ Time Frame: The primary analysis will occur 6 months after the last patient is randomised. the final analysis will occur at the earlier of 18 months after the last patient is randomised or when 70% of patients have progressed or died. ]
    Tumour size assessment in patients who cross over after progression on savolitinib plus placebo, defined as the percentage change from baseline in TLs at 12 weeks per RECIST 1.1 as assessed by the investigator.

  9. Total clearance in EGFR mutations at 6-weeks after therapy initiation (percentage and absolute change from baseline in EGFR mutation allele frequencies). [ Time Frame: The primary analysis will occur 6 months after the last patient is randomised. ]
    To determine the prevalence of ctDNA clearance after savolitinib plus osimertinib or savolitinib plus placebo treatment in this patient population

  10. Plasma concentrations of savolitinib, osimertinib and their metabolites, (M2 and M3 for savolitinib; AZ5104 for osimertinib) [ Time Frame: Cycle 1, Day 1: Pre-dose and 1 and 3 hours post-dose; Cycle 2, Day 1: Pre-dose and 1 and 3 hours post-dose; Cycle 3, Day 1: Pre dose and 1, 3, 4, and 6 hours post-dose; Cycles 6 and 11, Day 1: Pre-dose only. (Each Cycle is 28 days). ]
    To evaluate the PK of savolitinib and osimertinib.

  11. Time dependency of the PK of savolitinib, osimertinib and their metabolites, (M2 and M3 for savolitinib; AZ5104 for osimertinib) [ Time Frame: 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) ]
    To evaluate the PK of savolitinib and osimertinib.

  12. AUCss of savolitinib, osimertinib and their metabolites, (M2 and M3 for savolitinib; AZ5104 for osimertinib) [ Time Frame: Cycle 3, Day 1 (Each Cycle is 28 days) ]
    To evaluate the PK of savolitinib and osimertinib.

  13. Cssmax of savolitinib, osimertinib and their metabolites, (M2 and M3 for savolitinib; AZ5104 for osimertinib) [ Time Frame: Cycle 3, Day 1 (Each Cycle is 28 days) ]
    To evaluate the PK of savolitinib and osimertinib.

  14. Tssmax of savolitinib, osimertinib and their metabolites, (M2 and M3 for savolitinib; AZ5104 for osimertinib) [ Time Frame: Cycle 3, Day 1 (Each Cycle is 28 days) ]
    To evaluate the PK of savolitinib and osimertinib.

  15. CLss/F of savolitinib, osimertinib and their metabolites, (M2 and M3 for savolitinib; AZ5104 for osimertinib) [ Time Frame: Cycle 3, Day 1 (Each Cycle is 28 days) ]
    To evaluate the PK of savolitinib and osimertinib.

  16. Number and percentage of subjects with adverse events (AEs) in different categories: All AEs [ Time Frame: Continuous collection from First dose until study termination, on average 12 months ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  17. Number and percentage of subjects with adverse events (AEs) in different categories: Serious AEs [ Time Frame: Continuous collection from First dose until study termination, on average 12 months ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  18. Number and percentage of subjects with adverse events (AEs) in different categories: Causally related AEs [ Time Frame: Continuous collection from First dose until study termination, on average 12 months ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  19. Number and percentage of subjects with adverse events (AEs) in different categories: Discontinuations due to AEs [ Time Frame: Continuous collection from First dose until study termination, on average 12 months ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  20. Number and percentage of subjects with adverse events (AEs) in different categories: Deaths [ Time Frame: Continuous collection from First dose until study termination, on average 12 months ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  21. Number of subjects with at least one treatment emergent change in laboratory parameters in Albumin [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  22. Number of subjects with at least one treatment emergent change in laboratory parameters in Alkaline phosphatase [ Time Frame: Screening, weekly for first 5, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  23. Number of subjects with at least one treatment emergent change in laboratory parameters in ALT [ Time Frame: Screening, weekly for first 10, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  24. Number of subjects with at least one treatment emergent change in laboratory parameters in Amylase [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  25. Number of subjects with at least one treatment emergent change in laboratory parameters in AST [ Time Frame: Screening, weekly for first 10 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation(an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  26. Number of subjects with at least one treatment emergent change in laboratory parameters in Total bilirubin [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  27. Number of subjects with at least one treatment emergent change in laboratory parameters in Total Calcium [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  28. Number of subjects with at least one treatment emergent change in laboratory parameters in Creatinine [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  29. Number of subjects with at least one treatment emergent change in laboratory parameters in Glucose [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation(an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  30. Number of subjects with at least one treatment emergent change in laboratory parameters in Magnesium [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  31. Number of subjects with at least one treatment emergent change in laboratory parameters in Sodium [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  32. Number of subjects with at least one treatment emergent change in laboratory parameters in Potassium [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  33. Number of subjects with at least one treatment emergent change in laboratory parameters in Total Protein [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  34. Number of subjects with at least one treatment emergent change in laboratory parameters in BUN or urea [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  35. Number of subjects with at least one treatment emergent change in laboratory parameters in Lactate dehydrogenase [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  36. Number of subjects with at least one treatment emergent change in laboratory parameters in Haematocrit [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  37. Number of subjects with at least one treatment emergent change in laboratory parameters in Haemoglobin [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  38. Number of subjects with at least one treatment emergent change in laboratory parameters in Leucocyte cell count [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  39. Number of subjects with at least one treatment emergent change in laboratory parameters in Platelet count [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  40. Number of subjects with at least one treatment emergent change in laboratory parameters in Red blood cell count [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  41. Number of subjects with at least one treatment emergent change in laboratory parameters in Reticulocytes [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  42. Number of subjects with at least one treatment emergent change in laboratory parameters in Neutrophil count [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  43. Number of subjects with at least one treatment emergent change in laboratory parameters in Lymphocyte count [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.

  44. Number of subjects with at least one treatment emergent change in laboratory parameters in Eosinophil count [ Time Frame: Screening, weekly for first 5 weeks, then Day 1 of every cycle (each Cycle is 28 days) until treatment discontinuation (an average of 1 year) ]
    To evaluate the safety and tolerability of savolitinib plus osimertinib or savolitinib plus placebo.


Other Outcome Measures:
  1. HLA alleles associated with susceptibility to drug related AEs (such as but not limited to hypersensitivity). [ Time Frame: On Cycle 1 Day 1 only (each cycle is 28 days) ]
    To collect and store germline DNA for exploration of the role of HLA alleles in developmental toxicity.

  2. Overall survival, in patients who cross over after progression on savolitinib plus placebo [ Time Frame: The primary analysis will occur 6 months after the last patient is randomised. The final analysis will occur at the earlier of 18 months after the last patient is randomised or when 70% of patients have progressed or died. ]
    Defined as time from randomisation until the date of death due to any cause



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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
    • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04606771


Locations
Layout table for location information
United States, California
Research Site
Duarte, California, United States, 91010
Research Site
Sacramento, California, United States, 95817
United States, New York
Research Site
Brooklyn, New York, United States, 11220
Argentina
Research Site
Buenos Aires, Argentina, C1120AAT
India
Research Site
Mumbai, India, 400053
Research Site
Rohini, India, 110 085
Taiwan
Research Site
Taichung City, Taiwan, 402
Research Site
Taipei 112, Taiwan
Research Site
Taipei, Taiwan, 100
Research Site
Taipei, Taiwan, 235
Research Site
Taoyuan City, Taiwan, 333
Thailand
Research Site
Bangkok, Thailand, 10210
Research Site
Bangkok, Thailand, 10300
Research Site
Bangkok, Thailand, 10330
Research Site
Bangkok, Thailand, 10400
Research Site
Bangkok, Thailand, 10700
Research Site
Hat Yai, Thailand, 90110
Research Site
Khon Kaen, Thailand, 40002
Research Site
Muang, Thailand, 50200
Vietnam
Research Site
Ha Noi, Vietnam, 100000
Research Site
Hanoi, Vietnam, 100000
Research Site
Ho Chi Minh city, Vietnam
Sponsors and Collaborators
AstraZeneca
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04606771    
Other Study ID Numbers: D5084C00009
2020-000813-33 ( EudraCT Number )
First Posted: October 28, 2020    Key Record Dates
Last Update Posted: September 8, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria:

When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access.

For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Locally
Advanced
Metastatic
Carcinoma
Non-Small Cell Lung Cancer
Osimertinib
Tagrisso
Savolitinib
MET
EGFR
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action