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

NCT04606771 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: D5084C00009
• Study Type: interventional
• Target: 30
• Locations: 6 countries
• Sites: 21

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

Locally; Advanced; Metastatic; Carcinoma; Non-Small Cell Lung Cancer; Osimertinib; Tagrisso; Savolitinib; MET; EGFR

Outcome Measures

Primary Outcomes (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.

  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)

• Progression-free Survival (PFS)

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

• Duration of Response (DoR)

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

• Tumour Size Assessment (TSA)

  Baseline and 12 weeks.

• Overall Survival (OS)

  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)

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

  6-weeks after therapy initiation.

Study Arms (2)

Arm A

EXPERIMENTAL

Savolitinib 300 mg oral QD Osimertinib 80 mg oral QD

Drug: Osimertinib + Savolitinib

Arm B

EXPERIMENTAL

Savolitinib 300 mg oral QD Placebo to Osimertinib 80mg oral QD

Drug: Savolitinib + Placebo

Interventions

Osimertinib + Savolitinib DRUG

Osimertinib 80 mg oral QD Savolitinib 300mg oral QD

Arm A

Savolitinib + Placebo DRUG

Savolitinib 300mg Oral QD Placebo to Osimertinib 80mg oral QD

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (21)

Research Site

Duarte, California, 91010, United States

Location

Research Site

Sacramento, California, 95817, United States

Location

Research Site

Ciudad de Buenos Aires, C1120AAT, Argentina

Location

Research Site

Delhi, 110085, India

Location

Research Site

Mumbai, 400053, India

Location

Research Site

Taichung, 402, Taiwan

Location

Research Site

Taipei, 100, Taiwan

Location

Research Site

Taipei, 11217, Taiwan

Location

Research Site

Taipei, 235, Taiwan

Location

Research Site

Taoyuan, 333, Taiwan

Location

Research Site

Bangkok, 10210, Thailand

Location

Research Site

Bangkok, 10300, Thailand

Location

Research Site

Bangkok, 10330, Thailand

Location

Research Site

Bangkok, 10400, Thailand

Location

Research Site

Bangkok, 10700, Thailand

Location

Research Site

Hat Yai, 90110, Thailand

Location

Research Site

Khon Kaen, 40002, Thailand

Location

Research Site

Muang, 50200, Thailand

Location

Research Site

Hanoi, 100000, Vietnam

Location

Research Site

Hà Nội, 100000, Vietnam

Location

Research Site

Ho Chi Minh City, 700000, Vietnam

Location

Related Links

• CSR Synopsis Redacted
• CSP Redacted
• SAP Redacted

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Carcinoma

Interventions

osimertinib; 1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical Study Information Center

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: September 1, 2020
• First Posted: October 28, 2020
• Study Start: September 28, 2020
• Primary Completion: December 21, 2022
• Study Completion: March 30, 2026
• Last Updated: February 27, 2026
• Results First Posted: September 24, 2024

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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.

Locations

US (2); IN (2); TH (8); AR (1); VN (3); TW (5)