2O - SAVANNAH: Savolitinib (savo) + osimertinib (osi) in patients (pts) with EGFRm advanced NSCLC and METoverexpression (OverExp) and/or amplification (Amp) following progressive disease (PD) on osi

Background

Savo is an oral, potent and highly selective MET-TKI that when combined with osi, an oral, third-generation EGFR-TKI, may overcome acquired MET-driven resistance in EGFRm advanced NSCLC post-osi. We report primary results from the Ph 2 SAVANNAH study (NCT03778229), assessing the efficacy and safety of savo + osi in this setting.

Methods

Pts with EGFRm advanced NSCLC and MET OverExp and/or Amp after PD on osi received savo 300 mg BID + osi 80 mg QD. MET thresholds were initially MET IHC3+/≥50% (3+ intensity in ≥50% of tumour cells) or FISH5+ (≥5 MET gene copies or MET:CEP7 ratio ≥2) and then defined as MET IHC3+/≥90% (3+ intensity in ≥90% of tumour cells) or FISH10+ (≥10 MET gene copies). The primary efficacy population was defined as pts with PD on 1L osi and MET IHC 3 +/≥90% or FISH10+ who received savo 300 mg BID + osi. Primary endpoint: inv-assessed ORR. Secondary endpoints included ORR by BICR; DoR and PFS by inv and BICR. Safety was also evaluated. DCO: 23 Aug 2024. We report efficacy in the primary efficacy population and safety in all pts who received savo 300 mg BID + osi.

Results

Of 101 pts who received savo 300 mg BID + osi, 80 were in the primary efficacy population: median age 66 yrs; 70% female; 71% White; 60% ECOG PS 1; 39% brain metastases at study entry. Inv-assessed ORR was 56% (95% CI 45, 67) and BICR ORR was similar (Table). Gr ≥3 AEs occurred in 57% (Gr ≥3 TRAEs 32%); SAEs 31%; AEs leading to discontinuation of savo/osi 16%/12%. Most common all-grade AEs (>20%): peripheral oedema 58%, nausea 45%, diarrhoea 33%, vomiting 21%. No new safety concerns emerged.

Conclusions

After PD on 1L osi, savo 300 mg BID + osi was well tolerated and demonstrated clinically meaningful and durable response in pts with EGFRm advanced NSCLC with MET IHC 3+/≥90% and/or FISH10+ status. This combination offers a potential treatment option in this setting and is under further investigation in the ongoing Ph 3 SAFFRON study (NCT05261399).

Clinical trial identification

NCT03778229; release date: 19 December 2018.

Editorial acknowledgement

The authors would like to acknowledge Fiona Neylon, BSc, of Ashfield MedComms, an Inizio Company, and Caroline Allinson, BSc, contracted by Ashfield MedComms, an Inizio Company, for medical writing support that was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

M. Ahn: Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, MSD, Merck, Takeda, Daiichi Sankyo, Pfizer, Amgen, Yuhan, Alpha Pharmaceuticals, Genexin, Voronoi, Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, MSD, Merck, Takeda, Amgen, Yuhan, Daiichi Sankyo, Boehringer Ingelheim. T.M. Kim: Financial Interests, Personal, Advisory Board: AstraZeneca, Boryung, Janssen, Regeneron; Financial Interests, Personal, Advisory Role: AstraZeneca, Boryung, Hanmi, IMBDx, Janssen, Novartis, Takeda, Sanofi, Regeneron, Roche/Genentech, Samsung Bioepis; Non-Financial Interests, Personal, Other, Coordinating PI: Regeneron; Financial Interests, Institutional, Other, Local PI: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Black Diamond Therapeutics, Blueprint Medicines, Boryung, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Enliven Therapeutics, F. Hoffmann-La Roche Ltd./Genentech, Inc., Fore Therapeutics, Genmab, Hanmi, Janssen, Merck, MSD, Novartis, Regeneron, Sanofi, Takeda, Yuhan; Financial Interests, Personal, Other, Speaker, Consultant, Advisor: AstraZeneca, Daiichi Sankyo, HK inno.N, IMBDx, Janssen, Takeda, Samsung Bioepis; Financial Interests, Personal, Other, Steering Committee Member: AstraZeneca, Regeneron. L. Bonanno: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Roche, Novartis, MSD, Janssen, Takeda; Non-Financial Interests, Personal, Other, Coordinating PI: AstraZeneca; Financial Interests, Personal, Funding: AstraZeneca; Other, Personal, Invited Speaker, Financial and non-financial: AstraZeneca, Roche, MSD, Bristol Myers Squibb, Lilly, Novartis; Financial Interests, Personal, Other, Financial and non-financial: AstraZeneca; Financial Interests, Personal, Other, Local PI: Roche, Bristol Myers Squibb, MSD, Ose Immunotherapeutics, Arcus Biosciences PharmaMar; Other, Personal, Speaker’s

Bureau, Financial and non-financial: Roche, Bristol Myers Squibb, AstraZeneca, MSD, Merck, Lilly, Novartis; Non-Financial Interests, Personal, Other, Steering Committee Member: AstraZeneca. S. Cheng: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, AstraZeneca, Merck, Johnson & Johnson. S. Kim: Financial Interests, Personal, Advisory Board: Terapex; Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Janssen, Takeda; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Principal Investigator: Yuhan. M. Tiseo: Financial Interests, Personal, Advisory Role: AstraZeneca, MSD, Pfizer, Eli Lilly, Roche, Bristol Myers Squibb, Amgen, Sanofi, Merck, Boehringer Ingelheim, Takeda, Novartis, Janssen, Daiichi Sankyo; Financial Interests, Institutional, Funding: AstraZeneca, Boehringer Ingelheim; Financial Interests, Personal, Other, Travel funding: Amgen. Q.S. Chu: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AnHeart, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Genprix, GSK, Janssen, Merck, Novartis, Ocellaris, Pfizer, Roche, Takeda; Financial Interests, Personal, Advisory Role: AbbVie, Amgen, AnHeart, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Genprix, GSK, Janssen, Merck, Novartis, Ocellaris, Pfizer, Roche, Takeda; Non-Financial Interests, Personal, Other, Coordinating PI: GSK; Non-Financial Interests, Institutional, Funding: AbbVie, Amgen, Apollomics, Arrivent Biopharma, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly/Loxo, Esperas, Exactis, GSK, iTEOS, Medlink, Merck, Monte Rosa Therapeutics, Nuvalent, Pfizer, Prelude Therapeutics, Roche, Sanofi, SignalChem; Financial Interests, Personal, Invited Speaker: AstraZeneca, AbbVie; Non-Financial Interests, Institutional, Principal Investigator: AbbVie, Amgen, Apollomics, Arrivent Biopharma, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly/Loxo, Esperas, Exactis, GSK, iTEOS, Medlink, Merck, Monte Rosa Therapeutics, Nuvalent, Pfizer, Prelude Therapeutics, Roche, Sanofi, SignalChem; Financial Interests, Institutional, Other, Research funding: AstraZeneca. C. Proto: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Roche; Financial Interests, Personal, Funding: AstraZeneca, Roche, MSD, Pfizer, Celgene, Daiichi, Janssen, Spectrum Pharmaceutical; Other, Personal, Other, Travel funding: AstraZeneca, Roche, MSD, Bristol Myers Squibb, Janssen; Financial Interests, Institutional, Principal Investigator: AstraZeneca, Bristol Myers Squibb, Roche, Pfizer, Seagen, Johnson & Johnson, Daiichi, MSD, Lilly. A. Sacher: Non-Financial Interests, Personal, Advisory Board: Genentech, Amgen, Merck; Financial Interests, Institutional, Other, Local PI: AstraZeneca, Amgen, Genentech, Merck, Lilly, Pfizer, Bristol Myers Squibb, Spectrum, GSK, Iovance, CRISPR Therapeutics, BridgeBio, HotSpot Thearapeutics, AdaptImmune; Financial Interests, Personal, Other, Travel expenses: Amgen, Merck, Genentech-Roche. Y. Luo: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Pfizer, Bristol Myers Squibb, Ono Pharmaceutical, Roche; Financial Interests, Personal, Other, Speaker, Consultant, Advisor: AstraZeneca, Pfizer. C.S. Baik: Financial Interests, Institutional, Funding: Blueprint, Daiichi, Nuvalent, Black Diamond, AbbVie, Bristol Myers Squibb, TurningPoint, AstraZeneca, Lilly, Pfizer, Janssen, Boehringer Ingelheim, Ellipses; Financial Interests, Personal, Other, Speaker, Consultant, Advisor: AstraZeneca, Daiichi, Bristol Myers Squibb, Pfizer, Boehringer Ingelheim, Genentech, Janssen. L. Bazhenova: Other, Personal, Advisory Board, Honoraria: Bristol Myers Squibb, Johnson & Johnson, Boehringer Ingelheim, Genentech, Pfizer, Natera, Merck, AbbVie, Pfizer, Revolution Medicine, Anheart. J. Cadranel: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Daiichi, Pfizer, Janssen, MSD, Roche, Sanofi, Takeda; Non-Financial Interests, Institutional, Other, Coordinating PI: IFCT; Financial Interests, Institutional, Funding: AbbVie; Non-Financial Interests, Personal, Member: IASLC; Non-Financial Interests, Personal, Principal Investigator: Amgen, AbbVie, AstraZeneca, Daiichi, Pfizer, Janssen, MSD, Roche, Sanofi, Mirati, Takeda, Boehringer Ingelheim. J.C. Yang: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, AbbVie, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, Gilead Sciences, Inc., Janssen, Merck KGaA, MSD, Novartis, Pfizer, Regeneron, Takeda, Yuhan Pharmaceuticals, GSK, ArriVent, AnHeart Therapeutics, Black Diamond Therapeutics, Inc.; Financial Interests, Personal, Other, Coordinating PI: AstraZeneca, MSD, Dizal Pharmaceuticals; Financial Interests, Institutional, Funding: AstraZeneca, F. Hoffman-La Roche; Financial Interests, Personal, Other, Local PI: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, F. Hoffman-La Roche, Gilead Sciences, Inc., Janssen, Merck KGaA, MSD, Novartis, Takeda, Yuhan, ArriVent, Dizal Pharmaceuticals, Numab Therapeutics AG, Ispen; Non-Financial Interests, Personal, Member: ASCO, ESMO, IASLC; Financial Interests, Personal, Other, Steering Committee Member: Amgen, AstraZeneca, Bayer, Daiichi Sankyo, Eli Lilly, Janssen, Merck KGaA, MSD, Takeda, Yuhan, ArriVent, Dizal Pharmaceuticals, Black Diamond Therapeutics, Inc., Numab Therapeutics AG; Financial Interests, Personal, Other, Travel fees: Dizal Pharmaceuticals, AstraZeneca, Takeda. A. Gont: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. M. Haskins: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. W. Xu: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. F. de Marinis: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Bristol Myers Squibb, Roche/Genentech, Pfizer, Novartis, Takeda, Merck Serono, Amgen, Pierre Fabre, Regeneron; Financial Interests, Personal, Other, Honoraria: AstraZeneca, MSD, Bristol Myers Squibb, Roche/Genentech, Pfizer, Novartis, Takeda, Merck Serono, Amgen. All other authors have declared no conflicts of interest.