SAVANNAH is a global Phase II study of
The abstract presents results from an analysis of 193 efficacy evaluable patients
Results showed a trend toward improved response rates with increasing level of MET aberration. Across all patients in this analysis, objective response rate (“ORR”) was 32% [95% confidence interval (“CI”): 26-39%], median duration of response (“DoR”) was 8.3 months [95% CI: 6.9-9.7 months], and median progression-free survival (“PFS”) was 5.3 months [95% CI: 4.2- 5.8 months]. These results are consistent with the previously presented results from the TATTON global exploratory study in over 220 EGFR mutation positive NSCLC patients with MET amplified tumors following progression after treatment with any EGFR TKI.
Among the SAVANNAH patients
Findings based on the ongoing SAVANNAH study, and the previously presented TATTON Phase Ib/II study, supported the initiation of the SAFFRON global Phase III study in patients with EGFR-mutated, MET-driven, locally advanced or metastatic NSCLC whose disease progressed on first- or second-line treatment with TAGRISSO® as the most recent therapy. Patients will be prospectively selected for the higher level of MET aberration. The SAFFRON study will evaluate the efficacy and safety of savolitinib in combination with TAGRISSO® compared to pemetrexed plus platinum doublet-chemotherapy, the current standard-of-care treatment in this setting. Approximately 324 patients are planned to be randomized. If successful, the multi-regional clinical trial (“MRCT”) may support registration for this combination globally. Two registrational studies are ongoing in
Further details from SAVANNAH will be available at WCLC. Further details of the savolitinib WCLC updates are as follows:
Title: | MET Biomarker-based Preliminary Efficacy Analysis in SAVANNAH: savolitinib+osimertinib in EGFRm NSCLC Post-Osimertinib |
Presenter: | |
Other Authors: | |
Session: | EP08.02 - Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments |
Abstract No.: | EP08.02-140 |
Title: | SAFFRON: Ph3 Savolitinib + Osimertinib vs Chemotherapy in EGFRm NSCLC with MET Overexpression/Amplification Post-Osimertinib |
Presenter: | |
Other Authors: | |
Session: | EP08.02 - Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments |
Abstract No.: | EP08.02-138 |
Title: | SANOVO: A Phase 3 Study of Savolitinib or Placebo in Combination with Osimertinib in Patients with EGFR-mutant and MET Overexpressed NSCLC |
Presenter: | |
Other Authors: | Jingchang Li, |
Session: | EP08.02 - Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments |
Abstract No.: | EP08.02-063 |
About NSCLC, EGFR and MET Aberrations
Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.1 More than a third of the world’s lung cancer patients are in
Approximately 10-25% of NSCLC patients in the
MET is a tyrosine kinase receptor.11 Aberration of MET (amplification or overexpression) is present in both treatment naïve patients as well as being one of the primary mechanisms of acquired resistance to EGFR TKIs for metastatic EGFR-mutated NSCLC.12,13 Approximately 2-3% of NSCLC patients have tumors with MET exon 14 skipping alterations, a targetable mutation in the MET gene.14 Among patients
About Savolitinib (ORPATHYS® in
Savolitinib is an oral, potent, and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations) or gene amplification.
Savolitinib is marketed in
In 2011, following its discovery and initial development by
Savolitinib development in NSCLC
Phase II study of savolitinib monotherapy in MET Exon 14 skipping alteration NSCLC (NCT02897479) – The conditional approval in
Based on results of the TATTON and SAVANNAH studies below, several Phase III studies of savolitinib in combination with TAGRISSO® have been initiated, including SACHI, SANOVO and SAFFRON.
- SACHI Phase III study of savolitinib in combination with TAGRISSO® in patients
who have progressed following EGFR TKI treatment due to MET amplification (NCT05015608) – Initiated in the second half of 2021, this is a randomized, open-label study inChina in EGFR mutated NSCLC patients with MET amplified tumors following progression after treatment with any EGFR TKI. - SANOVO Phase III study of savolitinib in combination with TAGRISSO® in treatment-naïve patients with EGFR mutant positive NSCLC with MET overexpression (NCT05009836) – Initiated in the second half of 2021, this is a randomized, double-blinded study in
China in untreated, unresectable or metastatic patients with EGFR mutated NSCLC with MET overexpressed tumors. - SAVANNAH Phase II study of savolitinib in combination with TAGRISSO® in patients
who have progressed following TAGRISSO® due to MET amplification or overexpression (NCT03778229) – This is an open-label, global study in EGFR mutated NSCLC patients with MET amplified/overexpressed tumors following progression after treatment with TAGRISSO®. Results were accepted for presentation at the upcoming WCLC annual meeting. - SAFFRON Phase III study of savolitinib in combination with TAGRISSO® in patients
who have progressed following TAGRISSO® due to MET amplification or overexpression (NCT05261399) – This is a global Phase III study in patients with EGFR mutated, MET-driven, locally advanced or metastatic NSCLC whose disease progressed on first- or second-line treatment with TAGRISSO® as the most recent therapy. Patients will be prospectively selected for the higher level of MET aberration. The SAFFRON study will evaluate the efficacy and safety of savolitinib in combination with TAGRISSO® compared to pemetrexed plus platinum doublet-chemotherapy, the current standard-of-care treatment in this setting. Approximately 324 patients are planned to be randomized. If successful, the MRCT may support registration for this combination globally. - TATTON Phase Ib/II studies of savolitinib in combination with TAGRISSO® in patients
who have progressed following EGFR TKI treatment due to MET amplification (NCT02143466) – This global exploratory study included over 220 EGFR mutated NSCLC patients with MET amplified tumors following progression after treatment with any EGFR TKI. Results were published in Lancet Oncology21 and final analysis was presented at the 2021World Conference on Lung Cancer 22. Three cohorts with patients treated following progression on first- or second-generation EGFR TKI demonstrated an ORR of 64.7-66.7% and a median PFS of 9.0-11.1 months. The cohort of patients treated following progression on a first- and third-generation EGFR TKI demonstrated an ORR of 33.3% (95% CI 22.4-45.7), with a median PFS of 5.5 months (95% CI 4.1-7.7). The combination demonstrated encouraging anti-tumor activity and an acceptable risk-benefit profile.
Savolitinib development in kidney cancer
SAMETA Phase III study in combination with IMFINZI® PD-L1 inhibitor in MET-driven, unresectable and locally advanced or metastatic papillary renal cell carcinoma (“RCC”) (NCT05043090) – Based on the encouraging results of the SAVOIR monotherapy and CALYPSO combination therapy studies below, we initiated SAMETA, a global Phase III, open-label, randomized, controlled study of savolitinib plus IMFINZI® versus sunitinib monotherapy versus IMFINZI® monotherapy in patients with MET-driven, unresectable and locally advanced or metastatic papillary RCC.
SAVOIR randomized, controlled study of savolitinib monotherapy in MET-driven locally advanced or metastatic PRCC (NCT03091192) – Data from 60 patients in this global study of savolitinib monotherapy compared with sunitinib monotherapy in MET-driven papillary RCC was presented at the
CALYPSO study of savolitinib in combination with IMFINZI® PD-L1 inhibitor in RCC (NCT02819596) – This investigator initiated open-label Phase I/II study of savolitinib in combination with IMFINZI®, a PD-L1 antibody owned by AstraZeneca, evaluated the safety and efficacy of the savolitinib/IMFINZI® combination in patients with RCC. An analysis of 41 papillary RCC patients was presented at the 2021 ASCO Annual Meeting24, showing a confirmed response rate in 8 out of the 14 MET-driven patients, or 57%, with a median DoR of 9.4 months, median PFS of 10.5 months and median OS of 27.4 months. No new safety signals were seen.
Savolitinib development in gastric cancer and other cancer indications
Phase II study of savolitinib monotherapy in advanced or metastatic MET amplified gastric cancer (“GC”) or adenocarcinoma of the gastroesophageal junction (“GEJ”) (NCT04923932) – This is an open-label, two-cohort, multi-center study to evaluate the efficacy, safety and pharmacokinetics of savolitinib in locally advanced or metastatic GC or GEJ patients whose disease progressed after at least one line of standard therapy.
This trial follows multiple Phase II studies that have been conducted in
Savolitinib opportunities are also continuing to be explored in multiple other MET-driven tumor settings via investigator-initiated studies including colorectal cancer.
About
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the
CONTACTS
Investor Enquiries | |
+852 2121 8200 | |
+1 (973) 567 3786 | |
Media Enquiries | |
Solebury Trout | +1 (917) 570 7340 (Mobile) bmiles@troutgroup.com |
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Nominated Advisor | |
Panmure Gordon ( | +44 (20) 7886 2500 |
_____________________________________
1 World Health Organization.
2
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