作者
Y.-L. Wu,Q. Zhou,Y. Pan,X. Yang,Y. Zhao,G. Han,Q. Pang,Z. Zhang,Q. Wang,J. Yao,H. Wang,W. Yang,B. Liu,Q. Chen,X. Du,K. Cai,B. Li,J. Shuang,L. Song,W. Shi
摘要
BackgroundConsolidation immunotherapy (IO) after chemoradiation is the standard of care for stage III uNSCLC. Addition of IO-based induction therapy may further improve outcome, partly by enabling surgery. SHR-1701 is a novel anti-PD-L1/TGFβRII fusion protein. We assessed neoadjuvant SHR-1701 ± chemo, followed by surgery or RT in untreated stage III uNSCLC without EGFR/ALK alterations.MethodsPts were given 3 cycles of neoadjuvant SHR-1701 (30 mg/kg Q3W) ± chemo (paclitaxel 175 mg/m2 Q3W + carboplatin AUC=5 Q3W). Pts with PD-L1 TPS <50% received combo-therapy (arm A) and those with PD-L1 TPS ≥50% were randomized (1:1) to receive combo-therapy (arm B) or SHR-1701 alone (arm C). After assessment by MDT, pts received surgery or definitive RT (60 Gy/30 fractions) + concurrent cisplatin (30 mg/m2 QW), followed by SHR-1701 for 16 cycles. The primary endpoints were post-induction ORR and event-free survival (EFS).ResultsTable: LBA5Efficacy by study armArm A (n=88)Arm B (n=9)Arm C (n=10)Arm A+B (n=97)All pts (n=107)Post-inductionORR (95% CI),%55.7 (44.7-66.3)77.8 (40.0-97.2)40.0 (12.2-73.8)57.7 (47.3-67.7)56.1 (46.2-65.7)DCR (95% CI)*,%93.2 (85.7-97.5)88.9 (51.8-99.7)90.0 (55.5-99.7)92.8 (85.7-97.0)92.5 (85.8-96.7)Best overallORR (95% CI),%70.5 (59.8-79.7)77.8 (40.0-97.2)60.0 (26.2-87.8)71.1 (61.0-79.9)70.1 (60.5-78.6)mEFS (95% CI)†, mo18.2 (11.5-NR)11.8 (3.3-NR)NR (2.0-NR)14.9 (11.5-NR)18.2 (11.8-NR)Surgery conversion, n (%)21 (23.9)3 (33.3)3 (30.0)24 (24.7)27 (25.2)*Same results for best overall DCR. †Starting from the first study dose. Data cutoff was Jul. 31, 2022. Open table in a new tab ConclusionsSHR-1701 ± chemo showed promising antitumor activity with a tolerable safety profile in stage III uNSCLC. Some pts could switch from unresectable to resectable and get much better efficacy. Phase 3 investigation is warranted.Clinical trial identificationNCT04580498.Legal entity responsible for the studyJiangsu Hengrui Pharmaceuticals, Co., Ltd.FundingJiangsu Hengrui Pharmaceuticals, Co., Ltd.DisclosureY. Wu: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Lilly, Roche, Pfizer, Boehringer Ingelheim, MSD Oncology, Bristol Myers Squibb, Hengrui; Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, Boehringer Ingelheim, Takeda; Financial Interests, Personal, Research Grant: Boehringer Ingelheim, Roche, Pfizer, Bristol Myers Squibb. J. Shuang, L. Song, W. Shi: Financial Interests, Personal, Full or part-time Employment: Hengrui. All other authors have declared no conflicts of interest. BackgroundConsolidation immunotherapy (IO) after chemoradiation is the standard of care for stage III uNSCLC. Addition of IO-based induction therapy may further improve outcome, partly by enabling surgery. SHR-1701 is a novel anti-PD-L1/TGFβRII fusion protein. We assessed neoadjuvant SHR-1701 ± chemo, followed by surgery or RT in untreated stage III uNSCLC without EGFR/ALK alterations. Consolidation immunotherapy (IO) after chemoradiation is the standard of care for stage III uNSCLC. Addition of IO-based induction therapy may further improve outcome, partly by enabling surgery. SHR-1701 is a novel anti-PD-L1/TGFβRII fusion protein. We assessed neoadjuvant SHR-1701 ± chemo, followed by surgery or RT in untreated stage III uNSCLC without EGFR/ALK alterations. MethodsPts were given 3 cycles of neoadjuvant SHR-1701 (30 mg/kg Q3W) ± chemo (paclitaxel 175 mg/m2 Q3W + carboplatin AUC=5 Q3W). Pts with PD-L1 TPS <50% received combo-therapy (arm A) and those with PD-L1 TPS ≥50% were randomized (1:1) to receive combo-therapy (arm B) or SHR-1701 alone (arm C). After assessment by MDT, pts received surgery or definitive RT (60 Gy/30 fractions) + concurrent cisplatin (30 mg/m2 QW), followed by SHR-1701 for 16 cycles. The primary endpoints were post-induction ORR and event-free survival (EFS). Pts were given 3 cycles of neoadjuvant SHR-1701 (30 mg/kg Q3W) ± chemo (paclitaxel 175 mg/m2 Q3W + carboplatin AUC=5 Q3W). Pts with PD-L1 TPS <50% received combo-therapy (arm A) and those with PD-L1 TPS ≥50% were randomized (1:1) to receive combo-therapy (arm B) or SHR-1701 alone (arm C). After assessment by MDT, pts received surgery or definitive RT (60 Gy/30 fractions) + concurrent cisplatin (30 mg/m2 QW), followed by SHR-1701 for 16 cycles. The primary endpoints were post-induction ORR and event-free survival (EFS). ResultsTable: LBA5Efficacy by study armArm A (n=88)Arm B (n=9)Arm C (n=10)Arm A+B (n=97)All pts (n=107)Post-inductionORR (95% CI),%55.7 (44.7-66.3)77.8 (40.0-97.2)40.0 (12.2-73.8)57.7 (47.3-67.7)56.1 (46.2-65.7)DCR (95% CI)*,%93.2 (85.7-97.5)88.9 (51.8-99.7)90.0 (55.5-99.7)92.8 (85.7-97.0)92.5 (85.8-96.7)Best overallORR (95% CI),%70.5 (59.8-79.7)77.8 (40.0-97.2)60.0 (26.2-87.8)71.1 (61.0-79.9)70.1 (60.5-78.6)mEFS (95% CI)†, mo18.2 (11.5-NR)11.8 (3.3-NR)NR (2.0-NR)14.9 (11.5-NR)18.2 (11.8-NR)Surgery conversion, n (%)21 (23.9)3 (33.3)3 (30.0)24 (24.7)27 (25.2)*Same results for best overall DCR. †Starting from the first study dose. Data cutoff was Jul. 31, 2022. Open table in a new tab ConclusionsSHR-1701 ± chemo showed promising antitumor activity with a tolerable safety profile in stage III uNSCLC. Some pts could switch from unresectable to resectable and get much better efficacy. Phase 3 investigation is warranted. SHR-1701 ± chemo showed promising antitumor activity with a tolerable safety profile in stage III uNSCLC. Some pts could switch from unresectable to resectable and get much better efficacy. Phase 3 investigation is warranted.