LBA5 A phase II study of neoadjuvant SHR-1701 with or without chemotherapy (chemo) followed by surgery or radiotherapy (RT) in stage III unresectable NSCLC (uNSCLC)

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.