What side effects are associated with this type of intervention?

Common side effects of MET inhibitors like Savolitinib and EGFR inhibitors like Osimertinib include gastrointestinal issues (nausea, diarrhea), fatigue, and skin reactions (rash, dry skin). When used in combination, these drugs can also lead to more severe adverse events such as liver toxicity, renal impairment, and pneumonitis. Targeted therapies often have a more manageable side effect profile compared to traditional chemotherapy, but they can still cause significant toxicities that require careful monitoring and management.

What prior FDA approvals exist?

The FDA has approved several treatments involving EGFR inhibitors and MET inhibitors for cancer. Osimertinib, an EGFR inhibitor, is approved for the treatment of non-small cell lung cancer (NSCLC) with specific EGFR mutations. MET inhibitors like crizotinib and capmatinib have been approved for NSCLC with MET exon 14 skipping mutations. These approvals highlight the FDA's recognition of targeted therapies that inhibit specific molecular pathways in cancer treatment, similar to the investigational combination of Savolitinib (MET inhibitor) and Osimertinib (EGFR inhibitor) being studied for advanced NSCLC.

What other types of research exist?

Promising alternatives to Savolitinib in combination with Osimertinib for NSCLC patients include: 1) Pembrolizumab plus chemotherapy (platinum agent and pemetrexed) for advanced nonsquamous NSCLC, which has shown improved overall survival and progression-free survival in the KEYNOTE-189 trial. 2) Tremelimumab and Durvalumab plus chemotherapy, which is an acceptable frontline option for metastatic NSCLC lacking EGFR or ALK mutations. 3) Pembrolizumab monotherapy for patients with PD-L1 expression of 1% or higher, as shown in the KEYNOTE-042 trial.

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Small Molecule Kinase Inhibitor

Savolitinib + Osimertinib for Non-Small Cell Lung Cancer (SAFFRON Trial)

Phase 3

Recruiting

Led By Shun Lu, Prof,MD,PhD,

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically or cytologically confirmed locally advanced or metastatic NSCLC which is not amenable to curative therapy

MET overexpression and/or amplification in tumour specimen collected following progression on prior osimertinib treatment

Must not have

History or active leptomeningeal carcinomatosis

Participants currently receiving medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP)3A4 or strong inhibitors of CYP1A2

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approximately 55 months post first subject randomized

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a new drug combination for lung cancer patients whose previous treatment didn't work. The new drugs aim to block two pathways that help cancer grow, potentially making the treatment more effective.

Who is the study for?

This trial is for adults with advanced non-small cell lung cancer (NSCLC) that has worsened despite osimertinib treatment. Participants must have a specific EGFR mutation, MET overexpression/amplification, and be in good physical condition (ECOG 0 or 1). They cannot join if they have brain metastases, heart issues, liver cirrhosis, prior MET inhibitor use, serious infections like HIV/HBV/HCV, or recent live vaccines.

What is being tested?

The study compares the effectiveness of savolitinib combined with osimertinib against standard platinum-based chemotherapy in treating NSCLC after osimertinib failure. It aims to determine which treatment is safer and works better for patients who meet certain genetic criteria.

What are the potential side effects?

Potential side effects include typical chemotherapy-related issues such as nausea, fatigue, blood count changes; savolitinib may cause swelling or pain at the injection site and possible liver enzyme alterations. Osimertinib can lead to diarrhea and skin reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My lung cancer cannot be cured with surgery or radiation.

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My cancer showed MET overexpression after treatment with osimertinib.

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I can provide a formalin-fixed, paraffin-embedded (FFPE) tumor tissue sample.

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My cancer progressed after treatment with osimertinib.

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I am fully active or can carry out light work.

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My cancer has a specific EGFR mutation.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have or had cancer spread to the lining of my brain and spinal cord.

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I am not taking strong drugs or supplements that affect liver enzymes.

Select...

I have a history of serious liver disease or cirrhosis.

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I do not have heart problems or ECG changes that could affect my heart rhythm.

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My lung cancer is mainly squamous or is small cell type.

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I have had lung inflammation that needed steroids.

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I have been treated with savolitinib or similar drugs.

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I do not have any serious active infections like TB, HIV, or hepatitis.

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I have been treated with an EGFR inhibitor, but not Osimertinib.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately 55 months post first subject randomized

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approximately 55 months post first subject randomized

This trial's timeline: 3 weeks for screening, Varies for treatment, and approximately 55 months post first subject randomized for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression-free survival (PFS) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC who have progressed on osimertinib.

Secondary study objectives

Disease control rate (DCR) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.

Duration of response (DoR) / savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.

Objective response rate (ORR) savolitinib + osimertinib versus platinum doublet chemotherapy in participants with EGFR mutated, MET-overexpressed and/or amplified locally advanced or metastatic NSCLC who have progressed on treatment with osimertinib.

+7 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Savolitinib + OsimertinibExperimental Treatment2 Interventions

300 mg savolitinib BID plus 80 mg osimertinib QD

Group II: ChemotherapyActive Control3 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Savolitinib

2024

Completed Phase 2

~190

Osimertinib

2017

Completed Phase 4

~1120

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Targeted cancer therapies, such as MET inhibitors (e.g., Savolitinib) and EGFR inhibitors (e.g., Osimertinib), work by specifically blocking the molecular pathways that drive cancer cell growth and survival. MET inhibitors target the MET gene, which can be overexpressed or mutated in some cancers, leading to uncontrolled cell proliferation. EGFR inhibitors block the epidermal growth factor receptor, which is often mutated in non-small cell lung cancer, preventing the activation of downstream signaling pathways that promote tumor growth. These targeted approaches are significant for cancer patients as they offer a more personalized treatment strategy, potentially improving efficacy and reducing the side effects associated with conventional chemotherapy.

Metformin Adjunct With Antineoplastic Agents for the Treatment of Lung Cancer: A Meta-Analysis of Randomized Controlled Trials and Observational Cohort Studies.Current and Emerging Options in the Management of EGFR Mutation-Positive Non-Small-Cell Lung Cancer: Considerations in the Elderly.Retrospective Review of MET Gene Mutations.