World Lung 2023 – Impower-151 can’t repeat Impower-150’s lung cancer success

Back in 2020 Roche had designed Impower-151 as a China-focused phase 3 study to address regional differences in patients’ genetic composition, most importantly higher EGFR mutation prevalence, versus the US registrational Impower-150 trial. Both studies concerned a combination of Tecentriq with Avastin and chemo in first-line non-squamous NSCLC, but ‘151 has failed to repeat the success of ‘150. World Lung today heard that Impower-151’s primary endpoint of investigator-assessed PFS didn’t back the triplet versus Avastin plus chemo alone, and neither did analyses of overall survival or remission rates. EGFR mutation status plays an important role in first-line NSCLC, and Tecentriq’s US label based on Impower-150 is notable for mandating no EGFR or Alk aberrations; in contrast the corresponding EU approval says EGFR or ALK mutants must only have failed targeted therapy, meaning that they could theoretically get Roche's combo while still harbouring a secondary mutation. Dr Caicun Zhou, from Tongji University School of Medicine, told World Lung that the ‘151 results were “inconsistent” with ‘150. However, baseline differences are the giveaway: 53% of the ‘151 population was EGFR or ALK positive, versus just 14% of that in Impower-150. China anti-PD-(L)1 MAb approvals in 1st-line metastatic NSCLCApproval dateRegimenIndicationSupporting trialHansizhuang (serplulimab; Henlius (Fosun))Nov 2022Abraxane combo1st-line sq NSCLCAstrum-004Cejemly/Zojiemei (sugemalimab; Cstone)Dec 2021Chemo combo1st-line sq & non-sq NSCLCGemstone-302Annik (penpulimab; Akeso)Jan 2023Chemo combo1st-line squamous NSCLCAK105-302Baizean (tislelizumab; Beigene)Jun 2021Chemo combo1st-line non-squam NSCLCRationale-304Jan 2021Chemo combo1st-line squam NSCLCRationale-307Ailituo/AiRuiKa (camrelizumab; Jiangsu Hengrui)?Chemo combo1st-line squam NSCLCCameL-sqJun 2020Chemo combo1st-line non-squam NSCLCCameLTyvyt (sintilimab; Innovent Biologics)Jun 2021Gemzar combo1st-line squam NSCLCOrient-12Feb 2021Alimta combo1st-line non-squam NSCLCOrient-11Tuoyi (toripalimab; Shanghai Junshi Bioscience)Sep 2022Chemo combo1st-line non-squam NSCLCChoice-01Tecentriq (Chugai (Roche))Jun 2021Chemo combo1st-line non-squam NSCLCPossibly Impower-130Apr 2021Monotherapy1st-line PD-L1+ve (?%) NSCLCPossibly Impower-110Keytruda (Merck & Co/Taiho)Nov 2019Chemo combo1st-line squam NSCLCKeynote-407Oct 2019Monotherapy1st-line PD-L1+ve (≥1%) NSCLCKeynote-042Mar 2019Chemo combo1st-line non-squam NSCLCKeynote-189Source: OncologyPipeline & ApexOnco.