Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib

Titre officiel

A Phase II, Single Arm Study Assessing Efficacy of Osimertinib With Savolitinib in Patients With EGFRm+ MET+, Locally Advanced or Metastatic Non Small Cell Lung Cancer Who Have Progressed Following Osimertinib Treatment (SAVANNAH Study)

Sommaire:

This study (the SAVANNAH study) will investigate the efficacy of osimertinib in combination with savolitinib in patients with EGFRm+ and MET+, locally advanced or metastatic NSCLC who have progressed following treatment with osimertinib.

Description de l'essai

Primary Outcome:

  • Objective response rate (ORR) by investigator assessment in accordance with RECIST 1.1
Secondary Outcome:
  • Objective response rate (ORR) by investigator assessment in accordance with RECIST 1.1.
  • PFS by investigator assessment in accordance with RECIST 1.1.
  • Mean change from baseline in the European Organisation for Research and Treatment of Cancer (EORTC) 30-item core quality-of-life questionnaire (QLQ-C30), version 3 (QLQ-C30 v3).
  • Plasma concentrations of osimertinib, savolitinib and their metabolites.
  • Total clearance in EGFR mutations at 6-weeks after therapy initiation (percentage and absolute change from baseline in EGFR mutation allele frequencies).
  • AEs, SAEs and discontinuation rate due to AEs, as characterized and graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event [CTCAE] v5.
  • Overall Survival by investigator assessment in accordance with RECIST 1.1.
  • Duration of Response by investigator assessment in accordance with RECIST 1.1.
  • Percentage change in tumour size by investigator assessment in accordance with RECIST 1.1.
  • Mean change from baseline in the European Organisation for Research and Treatment of Cancer (EORTC) complementary 13-item quality-of-life questionnaire - lung cancer symptoms questionnaire (QLQ-LC13).
The combination of osimertinib with savolitinib in this study (the SAVANNAH study) will explore if the combination will overcome MET-amplification as a mechanism of resistance. The SAVANNAH study will investigate the efficacy of osimertinib in combination with savolitinib in patients with EGFRm+ and MET+, locally advanced or metastatic NSCLC who have progressed following treatment with osimertinib. Eligible patients will be those with histologically or cytologically confirmed diagnosis of EGFRm NSCLC that is locally advanced or metastatic and is not amenable to further surgery or radiation therapy with curative intent. The disease must have progressed following treatment with osimertinib. Patients must have confirmation of MET+ tumour by central FISH, central IHC or certain local NGS testing (requirements summarised in the main body of the protocol and fully explained in the Central Laboratory Manual). In patients centrally confirmed as MET+, MET+ is defined as a) high expression of MET (by IHC) and/or b) increased MET gene copy number (by FISH). Patients must not have received prior or current treatment with savolitinib or another MET inhibitor. All patients confirmed as eligible will begin treatment on Day 1 with osimertinib+savolitinib. Treatment will continue od in 28 day cycles until either objective disease progression, unacceptable toxicity occurs, consent is withdrawn or another discontinuation criterion is met.

Voir cet essai sur ClinicalTrials.gov

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