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Sensitizing and T790M mutant EGFR tyrosine kinase inhibition

CompoundOsimertinib

Area under investigation

EGFRm NSCLC

Scientific PillarTumor Drivers & Resistance Mechanisms

 

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SAVANNAH trial overview

Tumor

EGFRm and MET overexpressed and/or amplified (IHC3+/≥90% and/or FISH10+), locally advanced or metastatic NSCLC that progressed following 1L osimertinib treatment

Trial Identifier

NCT03778229

Phase

II

Stage

Metastatic, ≥2L

Regimen

Osimertinib + savolitinib; placebo + savolitinib

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Savolitinib, partnered with HUTCHMED

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SAVANNAH trial overview

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Target Overview

Targeted inhibition of tumors harboring activating mutations in epidermal growth factor receptor (EGFR) has helped to advance the treatment approach for advanced non-small cell lung carcinoma (NSCLC).

While the majority of these activating mutations also sensitize EGFR (EGFRm) to effective targeting by early-generation EGFR-tyrosine kinase inhibitors (TKIs), the emergence of a secondary resistance mutation (EGFR T790M) results in treatment-refractory NSCLC disease progression. Approximately 51%-68% of tumors that progress on a first- and second-generation EGFR TKI are EGFR T790M mutation positive.1-7

Compound Overview

Osimertinib is a third-generation, irreversible, CNS-active EGFR-TKI designed to selectively target both EGFR-sensitizing (ie, T790M, L858R and exon 19 deletion) and EGFR T790M-resistance mutations.1,8

Osimertinib is being clinically evaluated in EGFRm-containing NSCLC.

Mechanism of Action

  • Mechanism of Action

References

1. Cross DA, Ashton SE, Ghiorghiu S, et al. Cancer Discov. 2014;4(9):1046-1061. 2. Yu HA, Arcila ME, Rekhtman N, et al. Clin Cancer Res. 2013;19(8):2240-2247. 3. Oxnard GR, Arcila ME, Sima CS, et al. Clin Cancer Res. 2011;17(6):1616-1622. 4. Sun JM, Ahn MJ, Choi YL, et al. Lung Cancer. 2013;82(2):294-298. 5. Arcila ME, Oxnard GR, Nafa K, et al. Clin Cancer Res. 2011;17(5):1169-1180. 6. Kuiper JL, Heideman DA, Thunnissen E, et al. Lung Cancer. 2014;85(1):19-24. 7. Li W, Ren S, Li J, et al. Lung Cancer. 2014;84(3):295-300. 8. Planchard D, Jänne PA, Cheng Y, et al. N Engl J Med. 2023;389(21):1935-1948.

 

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SAVANNAH trial overview

Tumor

EGFRm and MET overexpressed and/or amplified (IHC3+/≥90% and/or FISH10+), locally advanced or metastatic NSCLC that progressed following 1L osimertinib treatment

Trial Identifier

NCT03778229

Phase

II

Stage

Metastatic, ≥2L

Regimen

Osimertinib + savolitinib; placebo + savolitinib

Visit ct.gov

Savolitinib, partnered with HUTCHMED

Study Locator

Explore further trial details, understand eligibility criteria and speak to clinical trial navigators for the SAVANNAH trial via the Lung Cancer Study Locator website.

Visit Study Locator

SAVANNAH Overview Modal

SAVANNAH trial overview

Take me to ClinicalTrials.Gov

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SAVANNAH trial overview

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Abbreviations

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  • 1L

    first line

  • 2L

    second line

  • ADC

    antibody drug conjugate

  • AE

    adverse event

  • AUC

    area under the curve

  • BICR

    blinded independent central review

  • CNS

    central nervous system

  • CPR

    complete pathological response

  • CRC

    colorectal cancer

  • CRT

    chemoradiotherapy

  • CT

    chemotherapy

  • CTCAE

    Common Terminology Criteria for Adverse Events

  • ctDNA

    circulating tumor DNA

  • DCR

    disease control rate

  • DFS

    disease-free survival

  • DoR

    duration of response

  • ECG

    electrocardiogram

  • ECOG PS

    Eastern Cooperative Oncology Group Performance Score

  • EFS

    event-free survival

  • EGFR

    epidermal growth factor receptor

  • EGFRm

    epidermal growth factor receptor mutation

  • EGFRwt

    epidermal growth factor receptor wild type

  • EORTC QLQ-C30

    European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire

  • Ex19del

    exon 19 deletion

  • FISH

    fluorescence in situ hybridization

  • FISH10+

    fluorescence in situ hybridization (MET copy ≥10)

  • Gy

    gray

  • HBV

    hepatitis B virus

  • HCV

    hepatitis C virus

  • HIV

    human immunodeficiency virus

  • HNSCC

    head and neck squamous cell carcinoma

  • HRQoL

    health-related quality of life

  • IASLC

    International Association For The Study Of Lung Cancer

  • ICR

    independent central review

  • IHC3+/≥90%

    3+ immunohistochemistry overexpression in 90% of tumor cells

  • ILD

    interstitial lung disease

  • IV

    intravenous

  • L858R

    exon 21 L858R point mutation

  • MET

    hepatocyte growth factor receptor

  • NEC

    large cell neuroendocrine carcinoma

  • NSCLC

    non-small cell lung cancer

  • OD

    once daily

  • ORR

    overall or objective response rate

  • OS

    overall survival

  • PD

    progressive disease

  • PFS

    progression-free survival

  • PFS2

    time to second progression or death

  • PFS24

    PFS at 24 months from randomization

  • PK

    pharmacokinetics

  • PO

    per oral

  • PS

    phosphatidylserine

  • PtCh

    platinum-based chemotherapy

  • Q*W

    every * weeks

  • Q3W

    every 3 weeks

  • QD

    once daily

  • R

    randomization

  • RECIST

    Response Evaluation Criteria in Solid Tumors

  • RECIST v1.1

    Response Evaluation Criteria in Solid Tumors version 1.1

  • RT

    radiotherapy

  • SBRT

    stereotactic body radiation therapy

  • SCLC

    small cell lung cancer

  • SoC

    standard of care

  • TDT

    time to discontinuation or death

  • TFST

    time to first subsequent therapy

  • TKI

    tyrosine kinase inhibitor

  • TNM

    tumor node metastasis staging

  • TNM8

    Tumor Node Metastasis 8th edition

  • tSCLC

    transformed small cell lung cancer

  • TSST

    time to start of second subsequent therapy

  • TTD

    time to treatment discontinuation

  • TTDM

    time to death or distant metastases

  • TTP

    time to progression

  • WHO

    World Health Organization

  • WHO PS

    World Health Organization performance status

  • WT

    wild type

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Veeva ID: Z4-84958 US-109129 DE-92568 Last Updated October 20263/26
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