Osimertinib + Savolitinib for Lung Cancer

(SAVANNAH Trial)

Not currently recruiting at 110 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 infections, Others

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

Compensation: Varies

Number of Visits: 2

Duration: Up to 15 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for certain types of advanced lung cancer. Researchers aim to determine the effectiveness of osimertinib (a targeted therapy) combined with savolitinib for patients whose cancer has worsened despite previous osimertinib treatment. The study includes two groups: one receiving both drugs and another receiving a placebo with savolitinib for comparison. Suitable candidates have advanced lung cancer with specific genetic changes and have experienced cancer progression after using osimertinib. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot take medications or supplements that strongly affect certain liver enzymes (CYP3A4 and CYP1A2) within 3 weeks of starting the study. It's best to discuss your current medications with the study team.

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

Research shows that combining osimertinib and savolitinib holds promise for lung cancer patients. Studies have found this combination to be generally safe and well-tolerated, with many patients responding well over time.

Osimertinib, also known as Tagrisso, is often used with other drugs to treat non-small cell lung cancer. It has demonstrated strong benefits in extending patient survival, with manageable side effects for most individuals.

Savolitinib has been tested with osimertinib in past trials, showing good results in terms of safety and effectiveness.

Overall, evidence suggests that this combination is relatively safe for individuals with certain types of lung cancer. However, like any treatment, potential side effects exist, so discussing these options with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of osimertinib and savolitinib for lung cancer because it targets cancer cells more precisely. Unlike standard treatments like chemotherapy, which attack both cancerous and healthy cells, osimertinib specifically targets mutations in the EGFR gene, which are common in certain lung cancers. Savolitinib adds another layer of precision by inhibiting the MET pathway, which can drive cancer growth when overactivated. This dual-target approach offers a promising strategy to not only enhance treatment effectiveness but also potentially reduce side effects by sparing healthy cells.

What evidence suggests that osimertinib + savolitinib could be an effective treatment for lung cancer?

Research shows that combining osimertinib and savolitinib may help treat certain lung cancers. In this trial, one group of participants will receive this combination. Past studies demonstrated that patients with specific types of advanced lung cancer responded well and for a long time to this combination. Osimertinib alone has already been proven to extend the lives of people with advanced lung cancer. Adding savolitinib appears to enhance these benefits. Early results suggest that this combination could be effective for those whose cancer has worsened after using osimertinib alone. Another group in this trial will receive a placebo alongside savolitinib to compare outcomes. ^{5 6 7 8 9}

Who Is on the Research Team?

Lecia V. Sequist

Principal Investigator

Massachusetts General Hospital

Myung-Ju Ahn, MD

Principal Investigator

Samsung Medical Centre Sungkyunkwan University School of Medicine

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/overexpression, who have seen their cancer progress after treatment with osimertinib. They must be in good physical condition, not have severe heart issues or uncontrolled hypertension, and women of childbearing potential must use effective contraception.

Inclusion Criteria

- Obtained within 2 years of submission for MET analysis;

- Sufficient tissue to meet the minimum tissue requirement defined in the current Laboratory Manual.

I can provide a tumor sample for testing or am willing to have one taken.

Exclusion Criteria

I have had a recent heart attack or severe chest pain.

My brain or spinal tumors are stable, cause no symptoms, and I haven't needed steroids for 2 weeks.

I have been treated with a MET inhibitor like savolitinib.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive osimertinib in combination with savolitinib or placebo in 28-day cycles until disease progression or unacceptable toxicity

Up to 15 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Osimertinib
• Savolitinib

Trial Overview The trial is testing the effectiveness of combining two drugs: osimertinib and savolitinib versus a placebo for patients whose NSCLC has worsened despite previous osimertinib treatment. The goal is to see if this combination can help control the disease better.

How Is the Trial Designed?

Group I: osimertinib + savolitinib Experimental Treatment 2 Interventions

osimertinib + savolitinib

Group II: placebo + savolitinib Placebo Group 2 Interventions

placebo + savolitinib

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

Hutchison Medipharma Limited

Industry Sponsor

Trials

104

Recruited

14,000+

Dr. Weiguo Su

Hutchison Medipharma Limited

Chief Executive Officer since 2022

PhD in Chemistry from Harvard University, BSc in Chemistry from Fudan University

Dr. Karen Atkin

Hutchison Medipharma Limited

Chief Medical Officer since 2023

MD from Harvard Medical School

Hutchison MediPharma

Collaborator

Trials

1

Recruited

370+

Published Research Related to This Trial

Osimertinib significantly improves disease-free survival (DFS) in adults with completely resected, early-stage EGFR mutation-positive non-small cell lung cancer (NSCLC), as shown in the pivotal ADAURA trial, regardless of prior adjuvant chemotherapy.

The treatment is well tolerated with a manageable safety profile, and it does not negatively impact health-related quality of life, making it a suitable option for adjuvant therapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. Frampton, JE.[2022]

Osimertinib is a third-generation EGFR tyrosine kinase inhibitor that effectively targets specific mutations in advanced non-small cell lung cancer (NSCLC), including the T790M mutation, leading to significantly longer progression-free survival compared to first-generation EGFR TKIs like erlotinib or gefitinib.

The benefits of osimertinib in prolonging progression-free survival were consistent across all patient groups, regardless of the type of EGFR mutation or the presence of CNS metastases, and it has a generally manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib as first-line therapy in advanced NSCLC: a profile of its use. Scott, LJ.[2020]

Osimertinib (Tagrisso) is an approved adjuvant treatment for non-small cell lung cancer patients with specific tumor mutations, highlighting its targeted therapeutic approach.

Common side effects of osimertinib include blood-related issues like leukopenia and thrombocytopenia, as well as gastrointestinal and skin reactions, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Drug for Lung Cancer. Aschenbrenner, DS.[2023]

In a phase Ib trial, the combination of osimertinib and savolitinib demonstrated effectiveness in treating non-small cell lung cancer, suggesting a potential new treatment strategy.

This trial indicates that combining these two targeted therapies may enhance treatment outcomes for patients with this type of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-Small Cell Lung Cancer Responds to Osimertinib plus Savolitinib. [2022]

Osimertinib (TAGRISSO) received accelerated FDA approval for treating metastatic non-small cell lung cancer with the EGFR T790M mutation, showing significant tumor response rates of 57% and 61% in two major trials involving 411 patients.

While osimertinib demonstrated promising efficacy, common side effects included diarrhea (42%) and rash (41%), with 28% of patients experiencing severe adverse events, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Khozin, S., Weinstock, C., Blumenthal, GM., et al.[2022]

In a patient-derived xenograft mouse model of EGFR mutation-positive non-small cell lung cancer, the combination of osimertinib and savolitinib showed significant antitumor activity, with savolitinib achieving up to 84% tumor regression when combined with a fixed dose of osimertinib.

Savolitinib alone demonstrated substantial antitumor effects, while osimertinib alone had minimal impact, highlighting the potential of savolitinib to overcome resistance mechanisms associated with MET amplification in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic/Pharmacodynamic Analysis of Savolitinib plus Osimertinib in an EGFR Mutation-Positive, MET-Amplified Non-Small Cell Lung Cancer Model. Jones, RDO., Petersson, K., Tabatabai, A., et al.[2023]

Osimertinib (Tagrisso) is a targeted therapy approved by the FDA for patients with metastatic non-small cell lung cancer (NSCLC) who have the EGFR T790M mutation and have progressed after previous treatments.

The drug received special designations from the FDA, including breakthrough therapy and priority review, highlighting its significance in treating resistant forms of NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Skoulidis, F., Papadimitrakopoulou, VA.[2022]

In a study of 46 treatment-naive patients with EGFR-mutated advanced non-small cell lung cancer, alternating therapy with osimertinib and afatinib resulted in a median progression-free survival of 21.3 months, indicating promising efficacy despite not meeting the primary endpoint of 12-month progression-free survival probability.

The treatment was generally well-tolerated, with common side effects including diarrhea (73.9%) and rash (63.0%), and only a few cases of serious pneumonitis, suggesting a manageable safety profile for this alternating therapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternating therapy with osimertinib and afatinib for treatment-naive patients with EGFR-mutated advanced non-small cell lung cancer: A single-group, open-label phase 2 trial (WJOG10818L). Hayashi, H., Yonesaka, K., Nakamura, A., et al.[2022]

In a retrospective analysis of 32 patients with EGFR T790M-mutant non-small-cell lung cancer, osimertinib showed a 50% objective response rate and a median progression-free survival of 11.3 months, indicating its efficacy in clinical practice.

The median overall survival was 18.3 months, with better outcomes observed in patients without cerebral metastases and those with better performance status, highlighting the importance of these factors in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. Knetki-Wróblewska, M., Kowalski, DM., Czyżewicz, G., et al.[2022]

Citations

1. 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 ... No information is available for this page.

2. 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 ... Over the past decade, TAGRISSO has consistently delivered strong survival benefits and tolerable safety across all stages of non-small cell lung ...

3. hutch-med.com hutch-med.com/sanovo-phiii-enrollment-completion/

HUTCHMED Completes Patient Enrollment of SANOVO ... The study will evaluate the efficacy and safety of TAGRISSO® in combination with ORPATHYS® comparing to TAGRISSO® alone, a standard-of-care ...

4. 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.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1525730425002803

Savolitinib Plus Osimertinib in Epidermal Growth Factor- ... We report safety and efficacy data from a phase 2 study assessing savolitinib plus osimertinib in epidermal growth factor receptor (EGFR)- ...

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. 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 ...

8. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/New-study-results-reinforce-TAGRISSO-osimertinib-as-the-backbone-therapy-for-EGFR-mutated-lung-cancer-across-stages-and-settings.html

New study results reinforce TAGRISSO® (osimertinib) as ... In LAURA Phase III trial, TAGRISSO continues to demonstrate improved overall survival trend in unresectable, Stage III setting.

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

Savolitinib plus osimertinib in epidermal growth factor ... CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3).