Savolitinib + Osimertinib for Lung Cancer

(CoC Trial)

Not currently recruiting at 28 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must be taking: Osimertinib

Must not be taking: CYP3A4 inducers, CYP1A2 inhibitors

Disqualifiers: Cardiac diseases, Active infection, Others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 34

Duration: Up to 25 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new combination of treatments for individuals with a specific type of lung cancer. Researchers aim to evaluate the effectiveness of the drugs savolitinib and osimertinib (a targeted therapy) together, compared to savolitinib with a placebo. It targets those with non-small cell lung cancer with certain mutations who have experienced cancer progression despite using osimertinib. Individuals treated with osimertinib but still facing advanced or spreading cancer might be suitable for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Do I need to stop my current medications to join the trial?

The trial requires you to stop taking any medications or herbal supplements that are strong inducers of CYP3A4 or strong inhibitors of CYP1A2, or CYP3A4 substrates with a narrow therapeutic range at least 2 weeks before starting the study. You should also avoid these during the study and for 3 months after the last dose.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that the combination of savolitinib and osimertinib is generally well tolerated. Research indicates that using these drugs together results in manageable safety profiles similar to each drug individually.

For savolitinib, one study reported that 62% of patients experienced significant side effects, with some encountering liver function issues. However, savolitinib has demonstrated a good safety record in patients with a specific type of lung cancer.

Osimertinib is known for its tolerable safety record. Specifically, one study found that about 22% of patients experienced serious side effects, which were mostly manageable. Common side effects include fatigue and skin problems.

Overall, the safety data for both drugs suggest that while potential side effects exist, they are generally expected and manageable with proper medical care. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Savolitinib is being combined with Osimertinib to tackle lung cancer in a new way. Unlike other treatments, which mostly focus on targeting the epidermal growth factor receptor (EGFR), Savolitinib targets the MET gene, which can drive cancer growth when mutated or amplified. This combination therapy aims to overcome resistance to current EGFR inhibitors by adding Savolitinib's unique mechanism of action. Additionally, by including a placebo group for Osimertinib, researchers can better understand the specific impact of Savolitinib in this setting.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research has shown that combining savolitinib and osimertinib can effectively treat certain lung cancers. In this trial, participants in Arm A will receive both savolitinib and osimertinib, a combination that significantly extends the time patients live without their cancer worsening. This is particularly true for patients with non-small cell lung cancer that has specific genetic changes known as EGFR mutations and MET amplifications, and who have already been treated with osimertinib. Participants in Arm B will receive savolitinib with a placebo to osimertinib. Savolitinib alone has demonstrated strong and lasting effects in similar cases. This suggests that adding savolitinib to osimertinib could benefit patients with these specific genetic markers in their cancer. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Adults with advanced non-small cell lung cancer (NSCLC) that has specific mutations (EGFRm+) and MET amplification, who have seen their disease progress after osimertinib treatment. They should have tried no more than three prior therapies, be in relatively good health with a life expectancy of at least 12 weeks, and agree to use contraception. Those with certain heart conditions, active infections like hepatitis or HIV, other cancers within the last five years, or severe illnesses are excluded.

Inclusion Criteria

You have a visible and measurable area of the disease that can be monitored during the trial.

I can care for myself and have not gotten worse in the past 2 weeks. Doctors expect me to live at least 12 more weeks.

My cancer progressed after treatment with osimertinib.

Exclusion Criteria

You currently have active hepatitis B or C.

I haven't taken any cancer drugs for my advanced lung cancer in the last 14 days, except for osimertinib.

I am allergic to osimertinib, savolitinib, or similar drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive savolitinib plus osimertinib or savolitinib plus placebo in 28-day cycles until progression or unacceptable toxicity

Up to 25 months

Visits every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Tumor assessments every 6 weeks up to 24 weeks, then every 8 weeks

Open-label extension (optional)

Participants initially on savolitinib plus placebo may cross-over to open-label savolitinib plus osimertinib after progression

Until further progression or unacceptable toxicity

What Are the Treatments Tested in This Trial?

Interventions

• Osimertinib
• Savolitinib

Trial Overview The trial is testing if adding Savolitinib to Osimertinib is better than adding a placebo for patients whose NSCLC has worsened despite previous Osimertinib therapy. Participants will receive either both drugs or one drug plus a placebo to see which combination is more effective in controlling cancer growth.

How Is the Trial Designed?

Group I: Arm B Experimental Treatment 1 Intervention

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

Group II: Arm A Experimental Treatment 1 Intervention

Savolitinib 300 mg oral QD Osimertinib 80 mg oral QD

Osimertinib is already approved in United States, European Union for the following indications:

Approved in United States as Tagrisso for:

• Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
• Metastatic EGFR T790M mutation-positive NSCLC

Approved in European Union as Tagrisso for:

• Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
• Metastatic EGFR T790M mutation-positive NSCLC

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Citations

1. hutch-med.com hutch-med.com/elcc25/

HUTCHMED Highlights Savolitinib SAVANNAH Phase II ... SAVANNAH Phase II trial demonstrated high and durable response rates with savolitinib plus TAGRISSO® in MET-high lung cancer, representing a promising ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40461383/

mutated advanced non-small cell lung cancer with MET ... Savolitinib 300 mg bid plus osimertinib demonstrated high, clinically meaningful and durable responses in patients with EGFR-mutated, advanced NSCLC.

3. hutch-med.com hutch-med.com/nmpa-full-approval-for-orpathys-savolitinib-for-met14-nsclc/

HUTCHMED Announces NMPA Full Approval for ... ORPATHYS® has demonstrated clear efficacy and tolerability in both first-line and second-line settings, underscoring its potential as a standard ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00157-7/fulltext

Savolitinib plus osimertinib in epidermal growth factor ... Savolitinib + osimertinib had activity in MET overexpressed/amplified EGFR-mutated NSCLC after progression on osimertinib.

5. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2025/new-study-results-reinforce-tagrisso-as-the-backbone-therapy-for-egfr-mutated-lung-cancer-across-stages-and-settings.html

New study results reinforce Tagrisso as the backbone ... In LAURA Phase III trial, Tagrisso continues to demonstrate improved overall survival trend in unresectable, Stage III setting

6. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2025/tagrisso-plus-chemotherapy-demonstrated-a-median-overall-survival-of-nearly-four-years.html

Tagrisso plus chemotherapy demonstrated a median ... Over the past decade, Tagrisso has consistently delivered strong survival benefits and tolerable safety across all stages of non-small cell lung ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39576954

A Systematic Review and Single-Arm Meta-Analysis Osimertinib was well tolerated with a frequency of grade 3 or more adverse events of 21.77% (95% CI, 6.24 to 43.33). Conclusion: Osimertinib ...

8. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/TAGRISSO-osimertinib-plus-chemotherapy-demonstrated-a-median-overall-survival-of-nearly-four-years-the-longest-benefit-ever-reported-in-a-global-Phase-III-trial-in-EGFR-mutated-advanced-lung-cancer.html

TAGRISSO® (osimertinib) plus chemotherapy ... TAGRISSO® (osimertinib) plus chemotherapy demonstrated a median overall survival of nearly four years, the longest benefit ever reported in a ...

9. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00367-0/fulltext

Osimertinib plus consolidative radiotherapy for advanced ... At a median follow-up of 35.7 months, median PFS was 32.3 months (95% CI, 21.9–51.7), median OS was 45 months (95% CI, 39.3–56.4), and median ...

10. tagrissohcp.com tagrissohcp.com/metastatic/flaura/safety-side-effects.html

Safety Profile of TAGRISSO® (osimertinib) for Metastatic ... There was one fatal case (0.7%), 3.5% Grade 3, 34% Grade 2, and 18% Grade 1 adverse reactions of ILD/pneumonitis in TAGRISSO-treated patients. For TAGRISSO- ...