2O IMpower010: Biomarkers of Disease-Free Survival (DFS) in a Phase III Study of Atezolizumab (atezo) Vs Best Supportive Care (BSC) after Adjuvant Chemotherapy in Stage IB-IIIA NSCLC

BackgroundIMpower010 met its primary DFS endpoint in PD-L1 TC ≥1% (SP263) stage II-IIIA NSCLC patients (pts) and all stage II-IIIA NSCLC pts (Felip, Lancet 2021). We report exploratory DFS outcomes by additional PD-L1 subgroups and EGFR/ALK status; we also assessed ctDNA status as a potential biomarker in this setting.MethodsEligible pts with resected (R0) stage IB-IIIA NSCLC received up to four 21-day cycles of chemo and were then randomised 1:1 to atezo 1200 mg Q3W (16 cycles) or BSC. Stratification factors included PD-L1 status by SP142. We analysed DFS by PD-L1 expression at different TC levels (SP263; <1%, ≥1%, 1-49%, ≥50%) and by EGFR/ALK status in stage II-IIIA pts. Plasma samples for ctDNA testing were collected after surgery but before adjuvant chemo and analysed using the Natera Signatera RUO assay.ResultsOf 1005 randomised pts, 979 (97%) were evaluable by SP263; of these, 859 had stage II-IIIA NSCLC. SP263 subgroups were balanced between arms. DFS improvement with atezo vs BSC was seen in all PD-L1+ subgroups (Table). When EGFR/ALK+ pts were excluded, numerical improvements in DFS HRs were seen in all PD-L1 subgroups except TC ≥50%, which remained at 0.43. 600 pts were ctDNA evaluable; of these, 534 had stage II-IIIA NSCLC. ctDNA+ prevalence increased with disease stage (IB, 9%; II, 14%; IIIA, 29%). ctDNA+ vs ctDNA− stage II-IIIA pts had worse prognosis; improved DFS with atezo vs BSC was seen in both ctDNA+ and ctDNA− stage II-IIIA pts, with greater benefit in PD-L1 TC ≥1% vs <1% pts.ConclusionsTable: 2OStage II-IIIA ptsSP263 BEPTC <1%TC ≥1%TC 1-49%TC ≥50%AtezoBSCAtezoBSCAtezoBSCAtezoBSCn181202248228133114115114mDFS, mo36.137.0NR35.332.831.4NR35.7HRa 95% CI0.970.72, 1.310.660.49, 0.870.870.60, 1.260.430.27, 0.68SP263 BEP excluding EGFR/ALK+n15415821319710794106103mDFS, mo37.137.0NR36.0NR36.0NR37.3HRa 95% CI0.920.65, 1.300.620.45, 0.860.820.54, 1.250.430.26, 0.71ctDNA BEPctDNA−ctDNA+TC <1%bTC ≥1%bTC <1%bTC ≥1%bAtezoBSCAtezoBSCAtezoBSCAtezoBSCn941061249815223637mDFS, moNRNRNR37.35.18.021.87.2HRa 95% CI0.950.60, 1.500.570.36, 0.900.880.40, 1.910.540.31, 0.93BEP, biomarker-evaluable population; NR, not reached. a Unstratified HR. b By SP263. Open table in a new tab Clinical trial identificationNCT02486718.Editorial acknowledgementMedical writing assistance for this abstract was provided by Kia C. E. Walcott, PhD of Health Interactions and funded by F. Hoffmann-La Roche, Ltd.Legal entity responsible for the studyF. Hoffmann-La Roche, Ltd.FundingF. Hoffmann-La Roche, Ltd.DisclosureC. Zhou: Financial Interests, Personal, Invited Speaker: Roche China, Lily China, Boehringer Ingelheim, Sanofi, C-Stone, Qilu, Hengrui, Innovent Biologics, LUYE Pharma, TopAlliance Bioscience Inc, Amoy Diagnostics. M. Das Thakur, W. Zou: Financial Interests, Personal, Full or part-time Employment: Roche. M.K. Srivastava: Financial Interests, Personal, Full or part-time Employment: Genentech/Roche; Financial Interests, Personal, Stocks/Shares: Genentech/Roche. H. Xu: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. M. Ballinger: Financial Interests, Personal, Full or part-time Employment: Genentech/Roche; Financial Interests, Personal, Stocks/Shares: Genentech/Roche. E. Felip: Financial Interests, Personal, Advisory Board: Pfizer, Merck Serono, Merck Sharp & Dohme, F. Hoffman-La Roche, Eli Lilly, Bristol Myers Squibb, AstraZeneca, AbbVie, Amgen, Bayer, Blue Print Medicines, Glaxo Smith Kline, Medical Trends, Peptomyc, Puma, Sanofi Genzyme, Syneos Health, Takeda; Financial Interests, Personal, Invited Speaker: PrIME Oncology, Springer, Touch Medical, Pfizer, Merck Serono, Janssen, Merck Sharpe & Dohme, F. Hoffmann-La Roche, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly; Financial Interests, Personal, Other, Grant: Grant for Medical Oncology Innovation (GOI); Financial Interests, Personal, Other, Grant: Fundacion Merck Salud. H. Wakelee: Financial Interests, Personal, Invited Speaker: AstraZeneca, Janssen, Daiichi Sankyo, Blueprint, Mirati, Helsinn; Financial Interests, Personal, Invited Speaker: Fishawack Facilitate LTD, Medscape, Research to Practice, MJH Holdings, Axis Medical Education, Nexus Oncology; Financial Interests, Personal, Other, Discussion of new data at conferences: Curio Science; Financial Interests, Personal, Writing Engagements: UpToDate; Financial Interests, Institutional, Other, Local PI for Clinical Trials: ACEA Biosciences, Arrys Therapeutics, AstraZeneca/Medimmune, Bristol Myers Squibb, Clovis Oncology, Novartis, Seagen, Xcovery; Financial Interests, Institutional, Other, Coordinating PI for Clinical Trial: Celgene; Financial Interests, Institutional, Other, Steering Committee Member for clinical trial: Genentech/Roche, Merck; Financial Interests, Personal, Officer, President Elect: International Association for the Study of Lung Cancer (IASLC); Financial Interests, Personal, Leadership Role, Executive Committee: ECOG-ACRIN. N.K. Altorki: Other, Institutional, Research Grant: NCI, DoD, AZ LLC, Janssen. M. Reck: Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Mirati, Merck, MSD, Novartis, Pfizer, Sanofi, Roche; Financial Interests, Personal, Other, Consultancy: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Mirati, Merck, MSD, Novartis, Pfizer, Sanofi, Roche. H. Tanaka: Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical, AstraZeneca, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, AstraZeneca, MSD, Bristol Myers Squibb, Ono Pharmaceutical. S. McCune: Financial Interests, Institutional, Principal Investigator: Genentech. V. McNally: Financial Interests, Personal, Full or part-time Employment: Genentech/Roche; Financial Interests, Personal, Stocks/Shares: Genentech/Roche. E. Bennett: Financial Interests, Personal, Full or part-time Employment: Roche/Genentech. B. Gitlitz: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech. S. Novello: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Takeda, Roche, AstraZeneca, Boehringer Ingelheim, Beigene, AMG, Eli Lilly, Glaxo Smith Kline; Financial Interests, Personal, Advisory Board: Sanofi, AstraZeneca, Eli Lilly, Glaxo Smith Kline, Novartis, Pfizer, Takeda, Roche. All other authors have declared no conflicts of interest. BackgroundIMpower010 met its primary DFS endpoint in PD-L1 TC ≥1% (SP263) stage II-IIIA NSCLC patients (pts) and all stage II-IIIA NSCLC pts (Felip, Lancet 2021). We report exploratory DFS outcomes by additional PD-L1 subgroups and EGFR/ALK status; we also assessed ctDNA status as a potential biomarker in this setting. IMpower010 met its primary DFS endpoint in PD-L1 TC ≥1% (SP263) stage II-IIIA NSCLC patients (pts) and all stage II-IIIA NSCLC pts (Felip, Lancet 2021). We report exploratory DFS outcomes by additional PD-L1 subgroups and EGFR/ALK status; we also assessed ctDNA status as a potential biomarker in this setting. MethodsEligible pts with resected (R0) stage IB-IIIA NSCLC received up to four 21-day cycles of chemo and were then randomised 1:1 to atezo 1200 mg Q3W (16 cycles) or BSC. Stratification factors included PD-L1 status by SP142. We analysed DFS by PD-L1 expression at different TC levels (SP263; <1%, ≥1%, 1-49%, ≥50%) and by EGFR/ALK status in stage II-IIIA pts. Plasma samples for ctDNA testing were collected after surgery but before adjuvant chemo and analysed using the Natera Signatera RUO assay. Eligible pts with resected (R0) stage IB-IIIA NSCLC received up to four 21-day cycles of chemo and were then randomised 1:1 to atezo 1200 mg Q3W (16 cycles) or BSC. Stratification factors included PD-L1 status by SP142. We analysed DFS by PD-L1 expression at different TC levels (SP263; <1%, ≥1%, 1-49%, ≥50%) and by EGFR/ALK status in stage II-IIIA pts. Plasma samples for ctDNA testing were collected after surgery but before adjuvant chemo and analysed using the Natera Signatera RUO assay. ResultsOf 1005 randomised pts, 979 (97%) were evaluable by SP263; of these, 859 had stage II-IIIA NSCLC. SP263 subgroups were balanced between arms. DFS improvement with atezo vs BSC was seen in all PD-L1+ subgroups (Table). When EGFR/ALK+ pts were excluded, numerical improvements in DFS HRs were seen in all PD-L1 subgroups except TC ≥50%, which remained at 0.43. 600 pts were ctDNA evaluable; of these, 534 had stage II-IIIA NSCLC. ctDNA+ prevalence increased with disease stage (IB, 9%; II, 14%; IIIA, 29%). ctDNA+ vs ctDNA− stage II-IIIA pts had worse prognosis; improved DFS with atezo vs BSC was seen in both ctDNA+ and ctDNA− stage II-IIIA pts, with greater benefit in PD-L1 TC ≥1% vs <1% pts. Of 1005 randomised pts, 979 (97%) were evaluable by SP263; of these, 859 had stage II-IIIA NSCLC. SP263 subgroups were balanced between arms. DFS improvement with atezo vs BSC was seen in all PD-L1+ subgroups (Table). When EGFR/ALK+ pts were excluded, numerical improvements in DFS HRs were seen in all PD-L1 subgroups except TC ≥50%, which remained at 0.43. 600 pts were ctDNA evaluable; of these, 534 had stage II-IIIA NSCLC. ctDNA+ prevalence increased with disease stage (IB, 9%; II, 14%; IIIA, 29%). ctDNA+ vs ctDNA− stage II-IIIA pts had worse prognosis; improved DFS with atezo vs BSC was seen in both ctDNA+ and ctDNA− stage II-IIIA pts, with greater benefit in PD-L1 TC ≥1% vs <1% pts. ConclusionsTable: 2OStage II-IIIA ptsSP263 BEPTC <1%TC ≥1%TC 1-49%TC ≥50%AtezoBSCAtezoBSCAtezoBSCAtezoBSCn181202248228133114115114mDFS, mo36.137.0NR35.332.831.4NR35.7HRa 95% CI0.970.72, 1.310.660.49, 0.870.870.60, 1.260.430.27, 0.68SP263 BEP excluding EGFR/ALK+n15415821319710794106103mDFS, mo37.137.0NR36.0NR36.0NR37.3HRa 95% CI0.920.65, 1.300.620.45, 0.860.820.54, 1.250.430.26, 0.71ctDNA BEPctDNA−ctDNA+TC <1%bTC ≥1%bTC <1%bTC ≥1%bAtezoBSCAtezoBSCAtezoBSCAtezoBSCn941061249815223637mDFS, moNRNRNR37.35.18.021.87.2HRa 95% CI0.950.60, 1.500.570.36, 0.900.880.40, 1.910.540.31, 0.93BEP, biomarker-evaluable population; NR, not reached. a Unstratified HR. b By SP263. Open table in a new tab BEP, biomarker-evaluable population; NR, not reached. a Unstratified HR. b By SP263. Clinical trial identificationNCT02486718. NCT02486718. Editorial acknowledgementMedical writing assistance for this abstract was provided by Kia C. E. Walcott, PhD of Health Interactions and funded by F. Hoffmann-La Roche, Ltd. Medical writing assistance for this abstract was provided by Kia C. E. Walcott, PhD of Health Interactions and funded by F. Hoffmann-La Roche, Ltd. Legal entity responsible for the studyF. Hoffmann-La Roche, Ltd. F. Hoffmann-La Roche, Ltd. FundingF. Hoffmann-La Roche, Ltd. F. Hoffmann-La Roche, Ltd.