148P A phase II study of tislelizumab plus chemotherapy in EGFR mutated advanced non-squamous NSCLC patients failed to EGFR TKI therapies: First analysis

Abstract

BackgroundAlthough EGFR tyrosine kinase inhibitors (TKI) have improved the survival of EGFR mutated NSCLC pts, drug resistance inevitably develops in almost all pts. Tislelizumab (tis), an anti-PD-1 mAb, has shown improved efficacy when combined with chemotherapy in pts with advanced EGFR-wt NSCLC with a tolerable safety profile. This study aims to evaluate the efficacy and safety of tis plus chemotherapy in EGFR-mut nsq-NSCLC pts failed to EGFR TKI therapies.MethodsThis multicenter, single-arm, phase II study enrolled pts with EGFR sensitizing mutations who have failed prior EGFR-TKI therapies. Pts were treated with tis plus carboplatin and nab-paclitaxel Q3W for up to 4 cycles, followed by tis plus pemetrexed maintenance therapy. Primary endpoint was 1-year PFS rate, and secondary endpoints included ORR, DCR and safety, etc. First analysis is planned at 7 weeks after 50% planned enrollment (33 pts) for early efficacy and safety.ResultsTable: 148PResponseTotal (N=32)EGFR mutation#Prior EGFR TKI treatmentprior anti-angiogenesis treatmentExon 19del (N=17)Exon 21 L858R (N=14)1/2nd and 3rd TKI (N=17)1/2nd or 3rd TKI (N=15)Yes (N=10)No (N=22)BoR, n (%)PR19 (59.4%)∗12 (70.6%)6 (42.9%)10 (58.8%)9 (60.0%)7 (70.0%)12 (54.6%)SD10 (31.3%)3 (17.7%)7 (33.3%)5 (29.4%)5 (33.3%)1 (10.0%)9 (40.9%)PD3 (9.4%)2 (11.8%)1 (7.1%)2 (11.8%)1 (6.7%)2 (20.0%)1 (4.6%)ORR19 (59.4%)12 (70.6%)6 (42.9%)10 (58.8%)9 (60.0%)7 (70.0%)12 (54.6%)DCR29 (90.6%)15 (88.2%)13 (92.9%)15 (88.2%)14 (93.3%)8 (80.0%)21 (95.5%)BOR, best overall response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR, disease control rate*Including 4 unconfirmed PR;#1 pts with exon 18 G719X was PR. Open table in a new tab ConclusionsTislelizumab plus chemotherapy has preliminarily shown a promising anti-tumor efficacy with manageable safety profile for EGFR TKI failure pts. Efficacy and safety of the combination will be continuously monitored.Clinical trial identificationNCT04405674.Legal entity responsible for the studyThe authors.FundingBeiGene (Beijing), Co. Ltd.DisclosureAll authors have declared no conflicts of interest. BackgroundAlthough EGFR tyrosine kinase inhibitors (TKI) have improved the survival of EGFR mutated NSCLC pts, drug resistance inevitably develops in almost all pts. Tislelizumab (tis), an anti-PD-1 mAb, has shown improved efficacy when combined with chemotherapy in pts with advanced EGFR-wt NSCLC with a tolerable safety profile. This study aims to evaluate the efficacy and safety of tis plus chemotherapy in EGFR-mut nsq-NSCLC pts failed to EGFR TKI therapies. Although EGFR tyrosine kinase inhibitors (TKI) have improved the survival of EGFR mutated NSCLC pts, drug resistance inevitably develops in almost all pts. Tislelizumab (tis), an anti-PD-1 mAb, has shown improved efficacy when combined with chemotherapy in pts with advanced EGFR-wt NSCLC with a tolerable safety profile. This study aims to evaluate the efficacy and safety of tis plus chemotherapy in EGFR-mut nsq-NSCLC pts failed to EGFR TKI therapies. MethodsThis multicenter, single-arm, phase II study enrolled pts with EGFR sensitizing mutations who have failed prior EGFR-TKI therapies. Pts were treated with tis plus carboplatin and nab-paclitaxel Q3W for up to 4 cycles, followed by tis plus pemetrexed maintenance therapy. Primary endpoint was 1-year PFS rate, and secondary endpoints included ORR, DCR and safety, etc. First analysis is planned at 7 weeks after 50% planned enrollment (33 pts) for early efficacy and safety. This multicenter, single-arm, phase II study enrolled pts with EGFR sensitizing mutations who have failed prior EGFR-TKI therapies. Pts were treated with tis plus carboplatin and nab-paclitaxel Q3W for up to 4 cycles, followed by tis plus pemetrexed maintenance therapy. Primary endpoint was 1-year PFS rate, and secondary endpoints included ORR, DCR and safety, etc. First analysis is planned at 7 weeks after 50% planned enrollment (33 pts) for early efficacy and safety. ResultsTable: 148PResponseTotal (N=32)EGFR mutation#Prior EGFR TKI treatmentprior anti-angiogenesis treatmentExon 19del (N=17)Exon 21 L858R (N=14)1/2nd and 3rd TKI (N=17)1/2nd or 3rd TKI (N=15)Yes (N=10)No (N=22)BoR, n (%)PR19 (59.4%)∗12 (70.6%)6 (42.9%)10 (58.8%)9 (60.0%)7 (70.0%)12 (54.6%)SD10 (31.3%)3 (17.7%)7 (33.3%)5 (29.4%)5 (33.3%)1 (10.0%)9 (40.9%)PD3 (9.4%)2 (11.8%)1 (7.1%)2 (11.8%)1 (6.7%)2 (20.0%)1 (4.6%)ORR19 (59.4%)12 (70.6%)6 (42.9%)10 (58.8%)9 (60.0%)7 (70.0%)12 (54.6%)DCR29 (90.6%)15 (88.2%)13 (92.9%)15 (88.2%)14 (93.3%)8 (80.0%)21 (95.5%)BOR, best overall response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR, disease control rate*Including 4 unconfirmed PR;#1 pts with exon 18 G719X was PR. Open table in a new tab BOR, best overall response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR, disease control rate *Including 4 unconfirmed PR; #1 pts with exon 18 G719X was PR. ConclusionsTislelizumab plus chemotherapy has preliminarily shown a promising anti-tumor efficacy with manageable safety profile for EGFR TKI failure pts. Efficacy and safety of the combination will be continuously monitored. Tislelizumab plus chemotherapy has preliminarily shown a promising anti-tumor efficacy with manageable safety profile for EGFR TKI failure pts. Efficacy and safety of the combination will be continuously monitored.