Osimertinib plus savolitinib for EGFR-mutated lung cancer with low-level MET amplification

Osimertinib Combined With Savolitinib in the Treatment of EGFR Mutated Osimertinib Resistant NSCLC With Low Copy Number MET Amplification

This trial tests whether adding savolitinib to osimertinib helps people with EGFR-mutant non-small cell lung cancer who became resistant to osimertinib and have low-level MET amplification.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Qingdao Central Hospital (Academic / other)
• Drugs / interventions: osimertinib, savolitinib, immunotherapy
• Locations: 1 site (Qingdao)
• Trial ID: NCT07322783 on ClinicalTrials.gov

What this trial studies

This is an open-label, single-arm, multicenter phase 2 trial enrolling patients with EGFR-mutant NSCLC who have progressed on osimertinib and have low-level MET amplification (MET copy number <5 by NGS or FISH). Participants receive osimertinib 80 mg daily plus savolitinib 400–600 mg daily with weight-based dosing and predefined dose-reduction rules for savolitinib. The trial focuses on objective response rate and safety, with progression-free survival and tolerability as important secondary outcomes. Treatment continues until disease progression or unacceptable toxicity.

Who should consider this trial

Good fit: Ideal candidates are adults with EGFR-mutant advanced or metastatic NSCLC who have progressed on osimertinib, have measurable disease, MET amplification copy number below 5 by FISH/NGS, ECOG 0–2, and adequate organ function.

Not a fit: Patients without MET amplification, whose resistance is driven by other mechanisms, or those with poor performance status or uncontrolled organ dysfunction are unlikely to benefit.

Why it matters

Potential benefit: If successful, the combination could shrink tumors and extend progression-free survival for patients with osimertinib-resistant EGFR-mutant NSCLC and low-level MET amplification.

How similar studies have performed: Prior studies combining savolitinib and osimertinib showed high response rates and longer progression-free survival in patients with high MET copy-number amplification, but use in low-copy cases is less well established.

Eligibility criteria

Inclusion Criteria:

* 1\. Histologically or cytologically confirmed incurable advanced or metastatic non-small cell lung cancer who resistant to resistant to osimertinib, chemo-immunotherapy or anti-angiogenesis.

  2\. At least 1 measurable lesion (RECIST 1.1). 3. MET amplification copy number below 5 by FISH. 4. Male or female patients age ≥18 years. 5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2. 6. Estimated OS ≥3 months. 7. Adequate hematologic and bone marrow functions. 8. Adequate renal and liver function. 9. Had recovered from all toxicities related to prior anticancer therapies to grade ≤ 2, except for patients with grade 2 nausea/vomiting and/or grade 2 diarrhea despite optimal supportive therapy who will not be allowed to participate in the study.

  10\. Willingness to use contraception by a method that is deemed effective by the investigator by both males and female patients of child bearing potential (postmenopausal women must have been amenorrhea for at least 12 months to be considered of non-childbearing potential) and their partners throughout the treatment period and for at least three months following the last dose of study drug.

  11\. Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the patient prior to any study-specific procedures).

  12\. Willingness and ability to comply with study procedures and follow-up examination.

Exclusion13. Any of the following cardiac criteria: screening period resting period QTC \> 470 milliseconds (clinical electrocardiograph report value; if a single time\> 470 milliseconds, take the average of 3 inspections); rhythm of resting electrocardiogram (ECG), any clinically important abnormality of conduction or morphology (e.g., complete left bundle branch block, Grade 3 heart block, Grade 2 heart block); family history of congenital long QT prolongation syndrome or long QT syndrome.

14\. Evidence of any serious or uncontrolled systemic disease; various chronic active infections such as hepatitis B (HBV-DNA ≥ 104 copy number/ml or 2000 IU/ml), hepatitis C and HIV; uncontrollable Hypertensive patients (requires 2 or more drugs to control blood pressure); unstable angina; angina pectoris within 3 months prior to study; congestive heart failure (NYHA class II or higher); myocardial infarction (NSTEMI or STEMI) history in 6 months before study enrollment; severe arrhythmia requiring medical attention; severe liver, kidney, gastrointestinal or metabolic diseases.

15\. Patients who are unable to taking drugs 16. Other malignancies need treatment; except effectively treated skin basal cell carcinoma, cutaneous squamous cell carcinoma, and/or effectively resected orthotopic cervical cancer and/or breast cancer.

17\. Female patients during pregnancy or lactation. 18. Previous allergies or intolerance to treatment with osimertinib and savolitinib.

19\. Any other condition or circumstance of that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.

Criteria:

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Where this trial is running

Qingdao

• Qingdao Central Hospital — Qingdao, China (Recruiting)

Study contacts

• Study coordinator: youxin Ji, md, phD

Conditions EGFR Positive Non-small Cell Lung Cancer; MET Amplification; Savolitinib; Osimertinib; Drug Resistant